Volume 23 No 03
20 January 2014
dapagliflozin
AstraZeneca, Bristol-Myers Squibb registered,
USA (diabetes)
AstraZeneca and Bristol-Myers Squibb announced on 8
January 2014 that the US FDA has approved dapagliflozin as a
treatment for type II diabetes in adult patients. Dapagliflozin
(FORXIGA; FARXIGA) is a sodium-glucose cotransporter 2
Approvals
Licensing
Pipeline
News from BiOncoTech
Products &
Biotechnology
Newly Reported
Drugs in R&D Focus
(SGLT2) inhibitor. The agent is available in Europe, including
in the UK and Germany, and is also approved in Australia,
Brazil, New Zealand and Mexico for the treatment of type II
diabetes. Bristol-Myers Squibb and AstraZeneca entered into an
agreement in January 2007 for the worldwide development and
commercialization of dapagliflozin.
Approvals
or V600K mutation. The decision was
based on the response rate and median
dabrafenib & trametinib
announced
on
with dabrafenib and trametinib in 202
patients with BRAF V600E and V600K
mutation-positive metastatic melanoma.
8
January 2014 that the US FDA has
approved trametinib (MEKINIST) for
use in combination with dabrafenib
(TAFINLAR)
for
the
treatment
phase I/II study comparing dabrafenib
monotherapy to combination therapy
GlaxoSmithKline
supplemental approval, USA
(melanoma)
GlaxoSmithKline
duration of response observed in a
The combination was granted accelerated
approval, depending on results from the
ongoing phase III COMBI-D trial. The
PDUFA target date for the dabrafenib
filing is 9 January 2014.
of
unresectable or metastatic melanoma
Trametinib is a selective allosteric MEK1/2
in adult patients with a BRAF V600E
(MAP kinase) inhibitor being developed
Product Phase
Changes Reported
in R&D Focus
20 January 2014
R &D FO C US dr ugne w s
R&D Focus Drug News
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20 January 2014
Approvals1
Products & Biotechnology
dabrafenib & trametinib. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
daclatasvir . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4
edoxaban. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4
indacaterol + glycopyrronium bromide. . . . . . . . . . . . . . . . . . . . . . . 4
lambrolizumab. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
raltegravir. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
REXTORO. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
RIXUBIS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
tiotropium bromide . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
umeclidinium bromide + vilanterol. . . . . . . . . . . . . . . . . . . . . . . . . 6
ADX N05. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6
ALN AS1 & ALN AT3 & patisiran. . . . . . . . . . . . . . . . . . . . . . . . . . . 6
antibody-drug conjugates, cancer, Endo/Mersana . . . . . . . . . . . . . . . 7
APN 311 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
BL 9020 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
BOW 015 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
BPZE 1 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
cancer therapy, ImmTAC, MedImmune/Immunocore & drug design
technology, ImmTAC, Immunocore . . . . . . . . . . . . . . . . . . . . . . . . . 8
drisapersen. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
drug design technology, zinc finger proteins, Sangamo BioSciences &
gene therapy, hemoglobinopathies, Sangamo BioSciences/
Biogen Idec . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
LNA . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9
LY 2951742. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9
MAb, PDGFR-beta, Regeneron/Bayer. . . . . . . . . . . . . . . . . . . . . . . . 9
MAbs, cancer, Adimab/FivePrime . . . . . . . . . . . . . . . . . . . . . . . . . 10
microRNAs, neurodegenerative diseases, InteRNA/UCB/
Bonn University. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10
mPGES-1 inhibitors, NovaSAID/Cadila. . . . . . . . . . . . . . . . . . . . . . 10
niche activators, TGF-beta 1, Scholar Rock/Johnson & Johnson. . . . . 10
OPT 302 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10
paclitaxel poliglumex. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11
palovarotene . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11
pegloticase. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11
phosphoinositide-dependent kinase-1 inhibitors, Sunesis . . . . . . . . . 11
pixantrone . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11
PROBODY-drug conjugates, cancer, CytomX/ImmunoGen. . . . . . . . . . 12
SNS 062 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12
Xib 13 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12
ACI 35. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13
ALS 8176. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13
amifampridine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13
AMPION. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14
ANAVEX 2-73 + donepezil . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14
ANB 020. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14
AP 611074. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14
APL 130277 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14
AR 13324 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15
ARGX 110 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15
BMN 270 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15
BRABAFEN . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15
CARBAVANCE . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16
CB 618 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16
collagenase clostridium histolyticum. . . . . . . . . . . . . . . . . . . . . . . 16
CRLX 101 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16
dabrafenib . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17
delafloxacin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17
dexpramipexole. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17
DM 199 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17
DP b99 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18
EB 1020 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18
EDP 788 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18
ENMD 2076. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18
GOVX B11 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18
LBR 101 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19
NKTR 171. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19
ornithine phenylacetate. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19
pracinostat. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19
PRO 140 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20
PRT 201. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20
PXVX 0200 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20
RX 3117 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20
samatasvir & simeprevir . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21
selective inhibitors of nuclear export, Karyopharm . . . . . . . . . . . . . 21
SGK1 inhibitors, Visionary Pharmaceuticals/BioBlocks. . . . . . . . . . . 21
TG 4010. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22
TRV 027. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22
vaccine, H1N1 influenza, Vaxart . . . . . . . . . . . . . . . . . . . . . . . . . . 22
VX 135 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22
WTX 101 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23
yttrium Y 90 clivatuzumab tetraxetan. . . . . . . . . . . . . . . . . . . . . . 23
Pipeline
Newly Reported Drugs in R&D Focus
24
Product Phase Changes Reported in R&D Focus
25
Licensing
6
12
BO 011. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12
BO 110. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13
Sourced from IMS LifeCycle R&D Focus.
© 2014 IMS Health Incorporated or its affiliates. All rights reserved.
13
3
R &D FO C US dr ugne w s
Contents
20 January 2014
R &D FO C US dr ugne w s
for the treatment of cancer. The product is available in the
previously-treated patients. Additional phase III trials of
USA for the treatment of unresectable or metastatic melanoma
daclatasvir are expected to start in early 2014.
in adult patients with a BRAF V600E or V600K mutation and
has been approved in Canada for the same indication; an
MAA seeking approval of the agent as monotherapy and in
combination with dabrafenib for the treatment of adult patients
with unresectable or metastatic melanoma with a BRAF V600
mutation has been submitted in the EU. Phase II evaluation
of trametinib is ongoing in patients with nonsmall cell lung
cancer (NSCLC) as a second-line therapy, and in combination
with dabrafenib in patients with colorectal cancer. Several
studies have been conducted in pancreatic cancer, leukemia,
multiple myeloma and solid tumors.
edoxaban
Daiichi Sankyo submitted for approval, USA
(stroke, thrombosis)
Daiichi Sankyo reported on 8 January 2014 that it
has submitted an NDA to the US FDA for edoxaban in
the reduction in risk of stroke and systemic embolic
events in patients with non-valvular atrial fibrillation
(NVAF), and as a therapy for deep vein thrombosis
Dabrafenib (TAFINLAR), a BRAF kinase inhibitor, is also
(DVT) or pulmonary embolism (PE) and prevention of
being developed as a treatment for cancer. The agent has
symptomatic venous thromboembolism (VTE) recurrence.
been launched in the USA, Canada, Australia and in the EU
The proposed trade name is SAVAYSA. The NDA is based
for the treatment of unresectable or metastatic melanoma in
on data from the ENGAGE AF-TIMI 48 and Hokusai-VTE
adult patients with a BRAF V600E mutation. An MAA seeking
phase III trials.
approval of dabrafenib in combination with trametinib for
the treatment of patients with unresectable or metastatic
melanoma with a BRAF V600 mutation has been submitted
to the EMA. A phase II trial in NSCLC is ongoing.
daclatasvir
Bristol-Myers Squibb Accelerated Assessment,
EU (hepatitis C)
Bristol-Myers Squibb reported on 8 January 2014 that the
EMA has validated for accelerated assessment an MAA for
daclatasvir, in combination with other drugs (including
sofosbuvir), as a therapy for adults with chronic hepatitis
Edoxaban, an oral, once-daily factor Xa inhibitor, is
available in Japan (under the trade name LIXIANA) for
the prevention of VTE after major orthopedic surgery. In
December 2013, a regulatory filing was submitted in Japan
for the agent as a therapy for symptomatic VTE in patients
with DVT and/or PE, and for use in patients with NVAF.
In January 2014, an MAA was submitted to the EMA for
edoxaban in the prevention of stroke and systemic embolic
events in patients with NVAF, and as a therapy for DVT or
PE and prevention of symptomatic VTE recurrence.
indacaterol + glycopyrronium
bromide
C virus (HCV) infection with compensated liver disease,
including genotypes 1, 2, 3 and 4. The filing includes use
Novartis registered, Canada (COPD)
of the agent as part of an all-oral, ribavirin-free regimen in
treatment-naive HCV genotypes 1, 2, 3 patients and those
Novartis reported on 13 January 2014 that Health
who have failed protease inhibitor treatment.
Canada approved QVA 149 (ULTIBRO BREEZHALER) on 23
Daclatasvir is an orally available HCV non-structural 5A
(NS5A) protein inhibitor. A regulatory filing is under review
in Japan for a daclatasvir-based regimen as a therapy for
patients with chronic HCV genotype 1b infection. A phase III
program, designated UNITY, is ongoing; daclatasvir is being
assessed as part of an all-oral three direct-acting antiviral
December 2013 for long-term, once-daily, maintenance
bronchodilator treatment of airflow obstruction in patients
with chronic obstructive pulmonary disease (COPD),
including emphysema and bronchitis. This approval was
based on data from the SHINE, ILLUMINATE, SPARK,
BRIGHT and ENLIGHTEN phase III trials.
regimen in different HCV-infected patient populations,
QVA
149
is
a
once-daily
fixed-dose
combination
including non-cirrhotic and cirrhotic treatment-naive, and
of indacaterol, a beta2 adrenoceptor agonist, and
4
Sourced from IMS LifeCycle R&D Focus.
© 2014 IMS Health Incorporated or its affiliates. All rights reserved.
lambrolizumab
Merck & Co submitted for approval, USA
(melanoma)
Merck & Co announced on 13 January 2014 that it has
initiated the rolling submission of a Biologics License
Application for the use of lambrolizumab in ipilimumabexperienced patients with advanced melanoma in the
USA; the submission is expected to be completed during
first half 2014. Lambrolizumab (MK 3475), a monoclonal
antibody targeting PD-1 being developed for the treatment
of advanced or metastatic cancer, is undergoing phase
III evaluation in advanced melanoma. A phase II/III
trial of the agent as monotherapy and a phase I/II trial
in combination with pazopanib are being conducted
in patients with nonsmall cell lung cancer (NSCLC) and
advanced renal cell carcinoma, respectively.
raltegravir
Merck & Co supplemental approval, USA
(HIV infection)
On 8 January 2014 Merck & Co announced that the US FDA
has granted supplemental approval for use of raltegravir
(ISENTRESS) oral suspension with other antiretroviral drugs
for the treatment of HIV-1 infection in patients four weeks
of age and older. Raltegravir, a dihydroxypyridopyrazine1,6-dione HIV-1 integrase inhibitor, is available in many
regions worldwide in combination with other anti-HIV
medications for the treatment of HIV-1 infection in children
and adolescents, and in treatment-naive and treatmentexperienced adult patients. Merck & Co anticipates the
launch of raltegravir oral suspension in the USA during third
quarter 2014.
Sourced from IMS LifeCycle R&D Focus.
© 2014 IMS Health Incorporated or its affiliates. All rights reserved.
20 January 2014
REXTORO
Clarus submitted for approval, USA (hormone
deficiency)
Clarus reported on 13 January 2014 that it has filed
an NDA with the US FDA for REXTORO as a testosterone
replacement therapy for patients with low testosterone
levels. In two phase III trials, at least 75% of men treated
with REXTORO achieved average serum testosterone levels
in the normal range of 100-1000 ng/dL. REXTORO is an
oral formulation of testosterone undecanoate, a prodrug
of testosterone.
RIXUBIS
Baxter submitted for approval, Japan
(hemophilia)
On 8 January 2014 Baxter announced that, on 26 December
2013, it filed an NDA in Japan for the use of RIXUBIS in
the prophylaxis of bleeding in patients of all ages with
hemophilia B. Data from the phase II/III and phase III
trials of the agent were included in this application.
RIXUBIS, a recombinant factor IX, is available in the USA
for the treatment of acute bleeding episodes in adults with
hemophilia B. A regulatory filing was submitted in the EU
for this indication in November 2013 and a supplemental
filing was submitted in the USA in December 2013 for use
in pediatric patients.
tiotropium bromide
Boehringer Ingelheim submitted for approval,
Japan (asthma)
On 6 January 2014 Nippon Boehringer Ingelheim (a
subsidiary of Boehringer Ingelheim) announced that it has
submitted a regulatory filing in Japan seeking approval
of tiotropium bromide (SPIRIVA) administered via a
RESPIMAT inhaler for the treatment of adults with asthma.
Tiotropium bromide, a long-acting, inhaled cholinergic
antagonist, is available in most major markets worldwide
as an inhaled therapy for chronic obstructive pulmonary
disease. Boehringer Ingelheim has filed MAAs in Europe for
the treatment of adults with asthma.
5
R &D FO C US dr ugne w s
glycopyrronium bromide, a long-acting muscarinic
antagonist, being developed for the treatment of COPD;
the combination is administered via a BREEZHALER
device. The product was approved in the EU for once-daily
maintenance treatment of COPD in September 2013 and
has subsequently been launched in Germany and the
Netherlands. In November 2013, the product was launched
in Japan for the treatment of COPD.
20 January 2014
R &D FO C US dr ugne w s
umeclidinium bromide + vilanterol
ALN AS1 & ALN AT3 & patisiran
GlaxoSmithKline, Theravance registered,
Canada (COPD)
Genzyme, Alnylam expansion of alliance
On 9 January 2014 GlaxoSmithKline and Theravance
announced that a fixed-dose combination of umeclidinium
bromide and vilanterol was approved in Canada on 23
December 2013, under the trade name ANORO ELLIPTA,
for the long-term, once-daily maintenance treatment of
airflow obstruction in patients with chronic obstructive
pulmonary disease (COPD), including chronic bronchitis and
emphysema. The fixed-dose combination of umeclidinium
bromide, a long-acting muscarinic antagonist, and
vilanterol, a long-acting beta adrenoceptor agonist (LABA),
administered using SkyePharma's ELLIPTA dry powder
inhalation device, has been approved in the USA and is
awaiting approval in the EU and Japan for the treatment
of COPD. Theravance and GlaxoSmithKline entered into an
agreement in November 2002 for the development and
commercialization of once-daily LABA products for the
treatment of COPD and asthma.
Licensing
ADX N05
Aerial BioPharma, Jazz Pharmaceuticals
licensing agreement
Jazz Pharmaceuticals and Aerial BioPharma announced
on 14 January 2014 that they have entered into an
agreement, granting Jazz Pharmaceuticals worldwide
rights to ADX N05, except in certain Asian countries
where SK biopharmaceuticals retains rights to the agent.
Under the terms of the agreement, Aerial BioPharma
will receive a US$125 million upfront payment. Aerial
BioPharma and SK biopharmaceuticals are eligible to
receive development-, regulatory- and sales-based
milestone payments, as well as tiered royalties on sales.
Aerial BioPharma previously acquired rights to ADX N05
from SK biopharmaceuticals.
Genzyme and Alnylam reported on 13 January 2014 that
they have signed an agreement for the development and
commercialization of Alnylam’s therapies for rare genetic
diseases, including the ‘5x15’ programs patisiran (ALN
TTR02), ALN TTRsc, ALN AT3 and ALN AS1. The agreement
provides Genzyme with rights to commercialize patisiran
worldwide excluding North America and Western Europe; this
is an expansion of an agreement signed in October 2012 under
which Genzyme acquired rights in Japan and other Asia-Pacific
countries. In addition, Alnylam and Genzyme will jointly develop
and commercialize ALN TTRsc in North America and Western
Europe and Genzyme will commercialize the product outside
these regions. Genzyme has an option to either co-develop/copromote ALN AT3 for the treatment of hemophilia and other rare
bleeding disorders in Alnylam’s region, or acquire a worldwide
license to ALN AS1 for the treatment of hepatic porphyrias; a
decision on exercise of the option will be made when clinical
proof-of-concept trials of the drugs have been completed.
Genzyme has an option until 2020, for the development and
commercialization, worldwide excluding North America and
Western Europe, of all Alnylam’s therapies for rare genetic
diseases; the option may be extended to 2021. Alnylam retains
rights to co-develop and co-commercialize its genetic medicine
pipeline in North America and Western Europe. Genzyme has an
option to acquire rights to a global license to one of Alnylam’s
future genetic medicine programs not currently defined as a
‘5x15’ program. Genzyme will acquire a 12% stake in Alnylam
by buying US$700 million of its stock. Genzyme will provide
Alnylam with funding for research and development, starting on
1 January 2015, for programs in which Genzyme has exercised
its options. Genzyme will pay global development expenses to
the proportion of 20% in programs (such as patisiran) in which
it will develop and commercialize in its rest of the world regions,
50% in programs that are being co-developed/co-promoted
(ALN TTRsc and potentially ALN AT3), and 100% in programs for
which Genzyme has an option for global rights (the future non‘5x15’ program and potentially ALN AS1). Alnylam is entitled to
receive milestone payments of up to US$75 million per product
for regional and co-development/co-promotion programs, and
ADX N05, an adrenergic regulator, is being developed
for the treatment of narcolepsy. A phase IIb trial has
been completed.
up to US$200 million per product for global programs. Alnylam
6
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is entitled to receive tiered double-digit royalties up to 20% on
net sales of products commercialized by Genzyme in its regions.
Patisiran and ALN TTRsc are iv and sc RNAi-based
transthyretin (TTR)-targeting therapeutics that use
Tekmira’s lipid nanoparticle technology. Patisiran is
being evaluated in a phase III trial in TTR-mediated
amyloidosis (ATTR) patients with familial amyloidotic
polyneuropathy (FAP). ALN TTRsc is being evaluated in
a pilot phase II trial in TTR cardiac amyloidosis patients
with familial amyloidotic cardiomyopathy (FAC). ALN
AT3, an sc RNAi therapeutic targeting antithrombin (AT),
utilizes Alnylam’s proprietary GalNAc-siRNA conjugate
delivery approach; a phase I trial in the treatment of
hemophilia is expected to start in early 2014. ALN AS1,
an aminolevulinate synthase 1 (ALAS-1)-targeted RNAibased therapy, is under preclinical evaluation in the
treatment of hepatic porphyrias.
antibody-drug conjugates, cancer,
Endo/Mersana
Endo, Mersana milestone payment
Mersana announced on 9 January 2014 that it has received
a second milestone payment from Endo for completing
pilot toxicology studies of a FLEXIMER-based antibodydrug conjugate (ADC), under an agreement signed
by the two companies in March 2012. The companies
are developing ADCs for the treatment of cancer that
comprise Endo’s monoclonal antibodies linked to Mersana’s
FLEXIMER biodegradable and bio-inert polymer loaded with
a cytotoxic agent. Preclinical evaluation is under way.
APN 311
Medison Pharma, Apeiron licensing agreement
Apeiron, Gen Ilac licensing agreement
On 9 January 2014 Apeiron reported that it has entered into
licensing agreements with Medison Pharma and Gen Ilac,
whereby Medison Pharma has acquired exclusive rights to
market and sell APN 311 in Israel and Gen Ilac has acquired
exclusive rights to these activities in Turkey. Further details
of the agreements were not disclosed. APN 311 is a chimeric
monoclonal antibody produced in CHO cells that targets the
Sourced from IMS LifeCycle R&D Focus.
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BL 9020
BioLineRx, JHL Biotech licensing agreement
On 8 January 2014 BioLineRx announced that it has
signed a collaboration agreement with JHL Biotech
regarding the development and commercialization of
BL 9020 for the treatment of type I diabetes. Under
the terms of the agreement, JHL Biotech will have
global manufacturing rights to BL 9020 as well as
development and commercialization rights in China
and Southeast Asia. BioLineRx will hold development
and commercialization rights in the rest of the world.
Both companies will have rights to all development
and regulatory data generated under the agreement
in order to commercialize BL 9020 in their respective
territories. In addition, each company will be entitled
to single-digit royalties on sales of BL 9020 in the
other’s respective territories.
BL 9020, a monoclonal antibody targeting the NKp46
receptor, is being developed for the treatment of type I
diabetes. The agent was identified under BioLineRx’s Early
Development Program. Preclinical evaluation is ongoing.
BOW 015
Ranbaxy, EPIRUS licensing agreement
On 8 January 2014 EPIRUS and Ranbaxy announced that
they have signed a licensing agreement under which
Ranbaxy acquires exclusive commercialization rights to
BOW 015 in various regions including India, South-East
Asia and North Africa. Under the terms of the agreement,
EPIRUS and Ranbaxy will first commercialize BOW 015
in India and then Ranbaxy will pursue registration and
commercialization of the product in other regions. EPIRUS
is eligible to receive upfront, milestone and royalty
payments over the term of the agreement.
BOW 015 is a potential biosimilar version of the chimeric
humanized tumor necrosis factor (TNF)-alpha targeted
7
20 January 2014
GD2 antigen on neuroblastoma cells. The antibody is being
developed for the treatment of children with high-risk
neuroblastoma. A European phase III trial of the agent in
patients with neuroblastoma was initiated in 2012.
R &D FO C US dr ugne w s
Profits will be shared equally for Genzyme's co-development/
co-promotion products in Alnylam’s regions; Alnylam will book
net sales revenues.
20 January 2014
R &D FO C US dr ugne w s
monoclonal antibody infliximab (REMICADE), being
developed for the treatment of inflammatory diseases,
including rheumatoid arthritis. EPIRUS submitted a
regulatory filing seeking approval of BOW 015 in India in
November 2013 and plans to submit regulatory filings in
other key emerging markets in 2014.
BPZE 1
INSERM, Institut Pasteur, ILiAD
Biotechnologies licensing agreement
INSERM clinical data (Phase I)
ILiAD Biotechnologies, INSERM (France) and Institut Pasteur
(France) announced on 8 January 2014 that they have signed
collaboration and worldwide licensing agreements regarding live
attenuated Bordetella pertussis vaccine technology, including
BPZE 1. The licenses cover patent rights from the National
University of Singapore and National University of Ireland
Maynooth. The three parties in the agreement will each provide
expertise and resources; financial details were not disclosed.
Data from a phase I trial of BPZE 1 conducted by INSERM in
Sweden demonstrated that the vaccine was safe and induced
immune responses targeting B pertussis in healthy males. BPZE
1 is a live attenuated B pertussis vaccine strain designed to
colonize the respiratory tract after intranasal administration.
cancer therapy, ImmTAC,
MedImmune/Immunocore & drug
design technology, ImmTAC,
Immunocore
Immunocore’s ImmTAC (immune mobilizing monoclonal T-cell
receptor against cancer) technology enables the production of
ImmTAC reagents, which are comprised of monoclonal T-cell
receptors (mTCRs) with high affinity for specific intracellular
antigens, fused to anti-CD3 antibodies. ImmTAC reagents bind
to and reside on target cells for extended periods of time,
covering the cell surface with anti-CD3 scFv moieties which
recruit T cells and result in cell death.
drisapersen
GlaxoSmithKline, Prosensa licensing
termination
On 13 January 2014 Prosensa and GlaxoSmithKline
announced that Prosensa has regained rights to
drisapersen from GlaxoSmithKline and retains rights to all
other programs for the treatment of Duchenne muscular
dystrophy (DMD) included in an agreement between the
two companies. This research and exclusive license option
agreement between Prosensa and GlaxoSmithKline, entered
into in October 2009, has thus been terminated.
Drisapersen is a 2-O-methyl phosphorothioate modified
antisense oligonucleotide being developed for the treatment
of DMD. Phase III evaluation has been completed.
drug design technology, zinc
finger proteins, Sangamo
BioSciences & gene therapy,
hemoglobinopathies, Sangamo
BioSciences/Biogen Idec
MedImmune, Immunocore licensing agreement
Sangamo BioSciences, Biogen Idec licensing
agreement
AstraZeneca announced on 8 January 2014 that its
subsidiary MedImmune and Immunocore have entered into
an agreement to develop ImmTAC drugs against selected
cancer targets, using Immunocore’s ImmTAC technology.
MedImmune and AstraZeneca will have rights to develop
and commercialize ImmTAC products issued from this
collaboration. For each target program, Immunocore will
receive a US$20 million upfront payment and is eligible
to receive up to US$300 million in development and
commercial milestone payments, as well as tiered royalties.
On 9 January 2014 Sangamo BioSciences and Biogen
Idec reported that they have entered into a collaboration
and licensing agreement to develop a treatment for
sickle cell disease and beta thalassemia using Sangamo
BioSciences' proprietary zinc finger nuclease (ZFP) genome
editing technology. Under the terms of the agreement,
Sangamo BioSciences has responsibility for research and
development through the first proof-of-concept-trial for
beta thalassemia while both companies will conduct
IND-enabling research for sickle cell disease. Biogen Idec
8
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LNA
Santaris Pharma, Isarna Therapeutics
licensing agreement
Roche, Santaris Pharma licensing agreement
Santaris Pharma announced on 8 January 2014 that
it has granted Isarna Therapeutics rights to access
its Locked Nucleic Acid (LNA) technology to develop
immunotherapeutics targeted against the cytokines
transforming growth factor (TGF) beta1, beta2 and
beta3. Under the terms of the agreement, Santaris
Pharma will receive an upfront payment and is eligible
for development, regulatory and sales milestones. In
addition, Santaris Pharma will receive a share of any
sub-licensing revenues and royalties on worldwide sales
of alliance products.
On 9 January 2014 Santaris Pharma announced that it
has signed an agreement with Roche regarding the use
of the LNA technology for the discovery and development
of RNA-targeted agents against disease targets in several
different areas. The development and commercialization
of the products discovered will be conducted by Roche.
Santaris Pharma is to receive an upfront US$10 million
cash payment and up to US$138 million in milestones, as
well as funding of ongoing R&D activities. Santaris Pharma
is also eligible for royalties on worldwide sales of products
arising from the collaboration.
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LY 2951742
Lilly reacquires rights from Arteaus
Lilly reported on 13 January 2014 that it has acquired all
rights to develop LY 2951742 from Arteaus. Financial terms
of the deal were not disclosed. LY 2951742, which was
discovered by Lilly, had been licensed to Arteaus which
was formed in 2011. LY 2951742, a monoclonal antibody
directed against calcitonin gene related peptide (CGRP), is
being developed for the prevention of frequent, recurrent
migraine. The antibody has been evaluated in a phase II
trial by Arteaus.
MAb, PDGFR-beta, Regeneron/
Bayer
Bayer, Regeneron licensing agreement
Bayer and Regeneron reported on 13 January 2014 that they
have signed an agreement for the joint development of an
antibody directed against platelet derived growth factor
receptor beta (PDGFR-beta), for use in combination with
aflibercept (EYLEA), as a therapy for wet age-related macular
degeneration (AMD). The terms of the deal stipulate that
Regeneron will receive a US$25.5 million upfront payment,
and is eligible to receive option and milestone payments
totalling up to US$40 million through regulatory approval. The
companies will share costs for worldwide development of the
antibody. Bayer will have exclusive rights to commercialize the
product in regions outside the USA; sales profits from these
ex-US regions will be shared jointly between the companies.
Bayer has responsibility for various payments to a third party,
including royalties on product sales outside the USA and a
share of development-based milestone payments. Regeneron
9
20 January 2014
LNA technology is based on synthetic analogues of
ribonucleic acid (RNA) in which the normally flexible ribose
sugar ring is fixed in a more rigid conformation through a
molecular bridge between two carbon atoms in the sugar
ring. LNA-containing drugs use the antisense principle to
block the function of specific RNAs within cells and tissues,
show high specificity and provide improved efficacy at lower
doses compared with drugs based on other technologies,
such as siRNA.
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will have responsibility for global clinical development
and commercialization of products resulting from the
collaboration and will provide Sangamo BioSciences with
an upfront payment of US$20 million and reimbursement
for both internal and external research and development
costs. Sangamo BioSciences is also eligible to receive
development, regulatory, commercialization and sales
milestone payments, up to a total of approximately
US$300 million, and double-digit royalties on sales, and
will retain an option to co-promote any licensed products
for beta thalassemia and sickle cell disease in the USA.
The companies will utilize ZFP technology to revert
expression of adult beta-globin to fetal gamma-globin in
hematopoietic stem cells (HSCs) isolated from patients,
allowing for an autologous HSC transplant.
20 January 2014
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has rights to commercialize the product in the USA, where it
will retain all sales profits. Clinical evaluation is expected to
start in early 2014.
MAbs, cancer, Adimab/FivePrime
FivePrime, Adimab licensing agreement
FivePrime reported on 9 January 2014 that it has entered into
a sponsored research collaboration agreement with Adimab to
develop fully-human monoclonal antibodies, initially for the
treatment of cancer. Under the terms of the agreement, Adimab
will use its proprietary discovery and optimization technology
to identify antibodies against a selection of targets specified
by FivePrime. Adimab will be eligible for potential research
funding, option and milestone payments, and royalties;
further financial details were not disclosed. FivePrime will
hold rights for the development and commercialization of
antibodies identified by this collaboration.
microRNAs, neurodegenerative
diseases, InteRNA/UCB/Bonn
University
Collaboration agreement between InteRNA
and Neuroallianz Consortium
On 10 January 2014 InteRNA announced that it has entered
into a collaboration agreement with the Neuroallianz
Consortium, an academic-industry partnership of which
Bonn University (Germany) and UCB are two members, to
investigate microRNAs (miRNAs) in neurodegenerative
diseases. Under the terms of the agreement, InteRNA will
utilize its multiparametric, high-throughput functional
screening assay technology for the identification and
validation of the role of miRNAs and novel targets in
neurodegenerative diseases.
mPGES-1 inhibitors, NovaSAID/
Cadila
Cadila, NovaSAID licensing agreement
NovaSAID and Cadila reported on 10 January 2014 that
they have established a collaboration for the preclinical
10
and clinical development of NovaSAID's microsomal
prostaglandin synthase-1 (mPGES-1) inhibitors for the
treatment of inflammation and pain in diseases such as
rheumatoid arthritis. Under the terms of the agreement,
Cadila has responsibility for all costs relating to the
program. Cadila will receive all revenue from the sale and
marketing of products in India, the Middle East and Africa;
the companies will share net sales in other regions.
niche activators, TGF-beta 1,
Scholar Rock/Johnson & Johnson
Johnson & Johnson, Janssen Biotech, Scholar
Rock collaboration agreement
On 8 January 2014 Scholar Rock reported that it has
entered into a research collaboration with Johnson &
Johnson and its subsidiary, Janssen Biotech, to discover
and develop niche activators targeting TGF-beta 1,
utilizing Scholar Rock's proprietary technology platform,
for the treatment of autoimmune diseases and cancers.
Under the terms of the agreement, Janssen Biotech has
an exclusive worldwide option to license, develop and
commercialize biologics generated by this collaboration.
Scholar Rock will be provided with research support and
is also eligible to receive option payments and preclinical,
clinical, regulatory and commercial milestone payments, in
addition to royalties on sales of each product marketed.
Niche activators are biologics which specifically regulate
growth factor signaling.
OPT 302
Opthea, Selexis licensing agreement
On 13 January 2014 Selexis announced that it has entered
into a commercial licensing agreement with Opthea,
a wholly-owned subsidiary of Circadian Technologies,
regarding the use of Selexis' CHO-M cell line and related
technologies for production of OPT 302. Further details of
the agreement were not disclosed.
Opthea is developing OPT 302 for the treatment of wet agerelated macular degeneration (wet AMD). OPT 302 is a soluble
form of human VEGF receptor 3 (VEGFR-3) which blocks the
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20 January 2014
pegloticase
paclitaxel poliglumex
On 10 January 2014 Crealta Pharmaceuticals announced
that it has acquired all of the assets of the company
formerly known as Savient from the bankruptcy court of
the district of Delaware (USA). The acquisition includes
Savient’s pegloticase (KRYSTEXXA), a PEGylated form of
recombinant porcine uricase, which is available in the USA
for the treatment of chronic gout in adult patients who are
refractory to conventional therapy and approved in the EU
for the treatment of severe debilitating chronic tophaceous
gout. Savient filed for bankruptcy in October 2013.
Novartis, Cell Therapeutics licensing
termination
On 13 January 2014 Cell Therapeutics announced that it
has regained all rights to paclitaxel poliglumex (OPAXIO)
from Novartis, following the termination of an agreement
between the two companies. Novartis is eligible to receive
sales-based payments, as well as payments based on any
sublicense and certain other amounts payable to Cell
Therapeutics. The initial agreement, entered into in 2006,
granted Novartis worldwide exclusive development and
commercialization rights to paclitaxel poliglumex.
Paclitaxel poliglumex, a water-soluble cancer therapy that links
paclitaxel to a polyglutamate polymer, is undergoing a phase
III trial as maintenance therapy in patients with ovarian cancer
and phase II evaluation in patients with malignant brain cancer.
palovarotene
Savient, Crealta Pharmaceuticals transfer of rights
phosphoinositide-dependent
kinase-1 inhibitors, Sunesis
Millennium, Sunesis licensing agreement
On 9 January 2014 Sunesis announced that it has entered
into an agreement with Millennium, granting Sunesis rights
to a program to develop phosphoinositide-dependent
kinase-1 (PDK1) inhibitors for the treatment of cancer.
Sunesis expects to select a lead development candidate to
take into IND-enabling studies in 2014.
Roche, Clementia licensing agreement
pixantrone
Clementia reported on 9 January 2014 that it signed a licensing
agreement with Roche under which Clementia has acquired
exclusive global rights to palovarotene. The terms of the
deal stipulate that Clementia has responsibility for further
development of the agent in any indication. Roche has received
an upfront fee, and is eligible to receive clinical- and regulatorybased milestone payments, and product sales-based royalties.
All regulatory, clinical and chemistry, manufacturing and
controls (CMC) materials have been transferred to Clementia.
Novartis, Cell Therapeutics licensing
termination
Palovarotene, a retinoic acid receptor-gamma (RARgamma)
agonist, is being developed by Clementia as a potential
treatment for fibrodysplasia ossificans progressiva. Roche
had conducted phase II trials of the agent in the treatment
of emphysema in chronic obstructive pulmonary disease
(COPD) patients; however, further development in this
indication was discontinued.
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Cell Therapeutics announced on 13 January 2014 that its
agreement with Novartis relating to pixantrone (PIXUVRI)
has been terminated. The agreement between the two
companies, entered into in 2006, granted Novartis an
option to acquire development and commercialization rights
to pixantrone. Under the termination, Cell Therapeutics
regains all rights to pixantrone and Novartis is eligible to
receive sales-based payments, as well as payments based
on any sublicense and certain other amounts payable to
Cell Therapeutics.
Pixantrone (PIXUVRI), a topoisomerase II inhibitor
which alkylates DNA, was granted conditional marketing
authorization in the EU for the treatment of adults with
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activity of VEGF-C and VEGF-D; the agent comprises three
extracellular domains of VEGFR-3 linked to the IgG1 Fc region.
Phase I evaluation is expected to begin early 2015.
20 January 2014
R &D FO C US dr ugne w s
multiple relapsed or refractory aggressive non-Hodgkin's
lymphoma (NHL) in May 2012 and has subsequently been
launched in several EU countries, including Germany.
PROBODY-drug conjugates, cancer,
CytomX/ImmunoGen
ImmunoGen, CytomX licensing agreement
CytomX and ImmunoGen reported on 9 January 2014 that
they have entered into a collaboration agreement to develop
PROBODY-drug conjugates (PDCs), using CytomX's PROBODY
platform and ImmunoGen's antibody-drug conjugate
technology, against a defined number of targets for the
treatment of cancer. Under the terms of the agreement,
each company will retain full control of PDCs developed
from its own target selection and will have responsibility
for preclinical and clinical evaluation, manufacture and
commercialization. The companies will each be entitled
to clinical and post-approval milestone payments from
the other, in addition to royalties on sales of all marketed
products generated through the collaboration. A PROBODY is
a masked monoclonal antibody that is inert in healthy tissue
but activated specifically in the tumor microenvironment.
SNS 062
Sunesis, Biogen Idec licensing agreement
that normalizes barrier function, was identified utilizing the
company's proprietary High Content Screen for endothelial
and epithelial membrane integrity. In a rat model of acute
lung injury undergoing allo-transplantation, treatment with
Xib 13 prevented graft failure at 28 days post-transplantation
and reduced lung edema by 61%. Toxicology studies showed
no major toxicities, and the agent was well tolerated up to a
dose of 1080 mg/kg daily. At BIO-Europe 2013, 4-6 November
2013, Vienna, Austria, Sonja Reingruber, CEO of Xiber Science,
informed R&D Focus that the company is looking for partners
to advance clinical development of Xib 13 for phase I/IIa.
Xiber Science plans to apply for Orphan Drug designation
for Xib 13 and estimates to complete phase I evaluation by
beginning 2016. Preclinical evaluation is ongoing.
For further information on the opportunities available,
contact:
Sonja Reingruber
CEO
Xiber Science GmbH
Josefigasse 24
2353 Guntramsdorf
Austria
Tel: +43 699 170 540 86
Email: [email protected]
Sunesis announced on 9 January 2014 that it has entered
into an agreement with Biogen Idec, granting Sunesis
exclusive rights to SNS 062. The agent is an oral Bruton’s
tyrosine kinase (Btk) inhibitor being developed for the
treatment of hematological cancers, including B-cell
malignancies. Preclinical evaluation is under way; Sunesis
plans to submit an IND application to the US FDA to start
clinical evaluation of SNS 062 beginning 2015.
Pipeline
Xib 13
At BIO-Europe 2013, 4-6 November 2013, Vienna, Austria,
Marisol Quintero, CEO of BiOncoTech, informed R&D
Focus that the company is developing BO 011, a human
antibody that targets pro-angiogenic protein Ephrin-B2,
for the treatment of cancer. In vitro assays showed that
BO 011 inhibited endothelial cell migration and tubular
structure formation and altered cell motility and the actin
cytoskeleton in single endothelial cells. The anti-Ephrin-B2
antibody reduced VEGF-induced neovascularization in
Xiber Science partnering opportunity,
Worldwide
Xiber Science is developing Xib 13, part of a family of peptide
analogues of cingulin (a key protein in tight junctions), for
the treatment of primary lung graft dysfunction, acute lung
injury and severe burns. Xib 13, an 11-amino acid peptide
12
News from BiOncoTech
BO 011
BiOncoTech preclinical data
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BO 110
ALS 8176
BiOncoTech partnering opportunity,
Worldwide
Alios phase change II, USA (respiratory
syncytial virus)
BiOncoTech is developing BO 110, an agonist of melanoma
differentiation-associated protein-5 (MDA-5), for the treatment
of aggressive cancers such as metastatic melanoma, glioblastoma
and pancreatic and bladder carcinomas. Preclinical evaluation
is under way. BiOncoTech plans to submit an IND application
and initiate clinical trials of BO 110 during second half 2014.
The company is interested in establishing partnerships for
the clinical development of the agent, Marisol Quintero, CEO
of BiOncoTech, informed R&D Focus at BIO-Europe 2013, 4-6
November 2013, Vienna, Austria.
For further information on the opportunities available,
contact:
Marisol Quintero
CEO
On 13 January 2014 Alios announced the initiation of a
randomized, double-blind, placebo-controlled phase IIa trial
(AL-8176-502) to assess the safety, pharmacokinetics and
antiviral activity of ALS 8176 against respiratory syncytial
virus (RSV) infection in a virus challenge model. This trial
will enroll approximately 66 healthy volunteers who will be
inoculated with RSV and given multiple oral doses of either
ALS 8176 or placebo for five days. Alios expects to complete
this trial by mid 2014. In a phase I trial evaluating the safety
and pharmacokinetics of single and multiple ascending oral
doses of ALS 8176 in adult healthy volunteers, no serious
adverse events or discontinuations due to adverse events
were reported. ALS 8176 was well tolerated.
Alios is developing ALS 8176, a nucleoside analogue
targeting respiratory syncytial virus (RSV) polymerase, for
the oral treatment of acute RSV infection.
BiOncoTech Therapeutics
Science Park of Valencia University
Catedrático Augustín Escardino 9
46980 Paterna
Valencia
amifampridine
BioMarin, Catalyst Pharmaceutical Partners
clinical data
Spain
AC Immune phase change I, Europe
(Alzheimer disease)
On 8 January 2014 Catalyst Pharmaceutical Partners reported
data from a cardiac safety trial comparing the effects of
amifampridine (FIRDAPSE) to those of placebo on the QT
interval in 59 healthy volunteers. This study met the prespecified primary endpoint; amifampridine did not affect
heart rate or cardiac depolarization at and above therapeutic
levels. None of the participants receiving amifampridine
developed new, clinically relevant electrocardiographic/
morphological alterations. In addition, there was no
significant effect of amifampridine on cardiac repolarization
as assessed using the QT interval.
AC Immune reported on 9 January 2014 the start of a
randomized, double-blind, placebo-controlled phase I trial
to evaluate two different doses of ACI 35 in patients with
Amifampridine, a potassium channel blocker that enhances
the release of acetylcholine, is available in several European
countries, including the UK, Germany, France and Italy; it
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13
Tel: +34 682 544 814
Email: [email protected]
Products & Biotechnology
ACI 35
20 January 2014
mild-to-moderate Alzheimer's disease. The primary objectives
of the trial are to assess the safety, tolerability of the vaccine,
and its immunogenicity. Secondary objectives are assessment
of biomarkers, and functional and clinical measures.
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Matrigel plug assays in athymic nude mice. In mice bearing
subcutaneous human tumor cell xenografts, inhibition of
Ephrin-B2 resulted in inhibition of tumor growth and tumor
lymphatic vasculature. Preclinical evaluation is under way.
20 January 2014
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was granted approval as an oral therapy for Lambert-Eaton
myasthenic syndrome (LEMS) in the EU in December 2009.
A global phase III registration trial of amifampridine in
patients with LEMS is ongoing. In October 2012, BioMarin
granted Catalyst Pharmaceutical Partners exclusive rights
to amifampridine in North America.
pharmacokinetics and clinical benefits of the combination
in patients with Alzheimer’s disease and other diseases
associated with dementia and cognitive impairment. In
animal models of Alzheimer’s disease, ANAVEX 2-73 in
combination with donepezil improved memory by up to
80% compared with ANAVEX 2-73 and donepezil alone.
AMPION
ANB 020
Ampio starts second phase III trial in
osteoarthritis
AnaptysBio preclinical data
On 13 January 2014 Ampio announced that it has initiated
a second randomized, placebo-controlled, double-blind
phase III trial, designated STEP, evaluating AMPION for the
treatment of osteoarthritis of the knee. The company aims
to enroll approximately 500 participants, who will receive
either 4 mL of AMPION via intra-articular injection or 4 mL of
saline vehicle. The clinical effects of AMPION will be evaluated
using The Western Ontario and McMaster Universities Arthritis
Index (WOMAC) and Patient’s Global Assessment (PGA) of
disease severity. In addition, cartilage regeneration will be
assessed in a subpopulation of the patients using MRI and
serum biomarkers. AMPION, a nonsteroidal anti-inflammatory
biologic, has potential in a range of inflammatory and
autoimmune diseases. One of the active ingredients of the
drug is aspartyl-alanyl diketopiperazine (DA-DKP), which
is derived from the two amino acids from the terminal end
of human albumin and is thought to have a key role in the
homeostasis of inflammation. The first phase III trial (SPRING)
evaluating AMPION for the treatment of osteoarthritis of the
knee is ongoing.
ANAVEX 2-73 + donepezil
Anavex Life Sciences trial planned,
Switzerland, USA (Alzheimer disease)
Anavex Life Sciences announced on 13 January 2014
that it has entered into an agreement with the Roskamp
Institute (USA) for the clinical development of ANAVEX
PLUS for the treatment of Alzheimer’s disease. ANAVEX
PLUS is a combination of ANAVEX 2-73, a tetrahydrofuranic
compound and sigma-1 receptor agonist, and donepezil
(ARICEPT), a reversible acetylcholinesterase inhibitor. The
planned clinical trial will evaluate the safety, tolerability,
14
On 10 January 2014 AnaptysBio announced that it has
initiated development of ANB 020, a lead candidate
antibody that targets IL-33, for the treatment of
inflammatory diseases mediated by Type 2 helper T (Th2)
cells, including atopic dermatitis, severe asthma, allergic
rhinitis and food allergies. The agent also has potential
for the treatment of chronic obstructive pulmonary disease
(COPD) and tissue fibrosis. ANB 020 was discovered using
AnaptysBio’s proprietary SHM-XEL platform.
AP 611074
Anaconda clinical data (Phase I/II) (genital
warts)
On 8 January 2014 Anaconda reported data from a phase
I/IIa trial of AP 611074 in patients with condyloma
(anogenital warts). Topical treatment with AP 611074 gel
for six weeks resulted in complete or partial regression
of anogenital warts. The agent showed a favorable safety
profile, with no cases of treatment discontinuation or
withdrawal from the trial, and the compliance rate was
high. AP 611074 is an inhibitor of human papillomavirus
(HPV) DNA replication being developed for the treatment
of condyloma, which is caused by HPV subtypes 6 and 11.
APL 130277
Cynapsus clinical data (Phase I)
On 13 January 2014 Cynapsus announced positive top-line
data from pilot crossover phase I trial (CTH-103) comparing
APL 130277, a sublingual thin film strip formulation
of apomorphine, to a commercially available injectable
formulation of apomorphine in 29 healthy volunteers. Tmax
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APL 130277 is being developed as a once-to-three times
a day rescue therapy to be used as an adjunct to levodopa
combination therapies for the treatment of moderate-tosevere Parkinson’s disease.
AR 13324
Aerie clinical data (Phase I)
On 9 January 2014 Aerie announced top-line results
from an open-label phase I trial assessing the ocular
and systemic safety and systemic absorption of 0.02%
AR 13324 ophthalmic solution in healthy volunteers. A
total of 18 participants received once-daily AR 13324 for
eight days. The pharmacokinetic results demonstrated very
low systemic exposure to AR 13324, with blood levels at
or below the limit of detection of 0.1 ng/mL at all time
points. There were no drug-related effects on systemic
safety parameters, including blood pressure and heart
rate. All subjects had intraocular pressure (IOP) in the
normotensive range of 12 to 21 mmHg. The average diurnal
IOP before dosing was approximately 16 mmHg and after
dosing it reduced to approximately 11 mmHg.
Aerie is developing AR 13324 for the treatment of glaucoma.
The agent has a double mechanism of action, lowering IOP
by enhancing fluid outflow through the trabecular pathway
while decreasing fluid inflow to the eye. AR 13324 has
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ARGX 110
arGEN-X provides update on development
On 13 January 2014 arGEN-X announced that it has initiated
the open-label, safety and efficacy expansion portion of its
phase Ib trial of ARGX 110 in up to 75 participants. The
company aims to assess the safety of ARGX 110 in CD70positive cancer patients with either hematological or solid
tumors as well as to evaluate efficacy in order to select
indications to be studied in future phase II trials. Top-line
data are expected to be released in first quarter 2015.
ARGX 110 is a fully human monoclonal antibody targeting CD70,
being developed for the treatment of cancer, autoimmune
diseases and inflammation. The antibody was generated using
arGEN-X’s SIMPLE Antibody proprietary platform.
BMN 270
BioMarin selects clinical candidate
(hemophilia A)
On 13 January 2014 BioMarin announced that it has
selected BMN 270, an adeno-associated virus (AAV)-factor
VIII vector, as a clinical candidate for the treatment of
hemophilia A and has initiated IND-enabling studies. In
mouse models of factor VIII deficiency, BMN 270 restored
plasma factor VIII levels to those adequate for normal
clotting in humans. BioMarin plans to initiate clinical
trials of BMN 270 in early 2015. In February 2013 BioMarin
licensed its gene therapy program for hemophilia from
University College London (UK) and St Jude Children’s
Research Hospital (USA).
BRABAFEN
Brabant Orphan Drug, USA, EU (Dravet
syndrome)
Brabant announced on 9 January 2014 that BRABAFEN, a
low-dose formulation of fenfluramine, has received Orphan
15
20 January 2014
been shown to inhibit activity of Rho-kinase (ROCK) and
the norepinephrine transporter. Aerie expects to start two
phase III registration trials of AR 13324 by mid 2014.
R &D FO C US dr ugne w s
was 31 and 40 min for 10 and 15 mg doses of APL 130277,
respectively, and 27 and 24 min for subcutaneous injections
of 2 and 3 mg apomorphine, respectively. An average
minimum threshold plasma exposure of approximately 3
ng/ml was achieved with the sublingual thin film strip
delivery system. The uptake of apomorphine was rapid and
similar to that of APOKYN (between ten and 60 min). The
mean time to reach a plasma concentration of apomorphine
associated with therapeutic benefit was ten to 13 min
for the two doses of APL 130277 and four to five min for
subcutaneous injection. The sublingual thin film strips also
demonstrated proportionality between the doses and were
better tolerated with fewer and less intense adverse events
than the subcutaneous injection. The side effects observed
with 15 mg APL 130277 were mild-to-moderate but not
dose limiting. Cynapsus expects to complete initial efficacy
trials of APL 130277 by end 2014 and a safety trial by end
2015, with an NDA filing expected in first half 2016.
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Drug designation for the treatment of Dravet syndrome in
the USA and the EU. Brabant plans to initiate phase III
trials of BRABAFEN in the same indication during second
half 2014. The agent has been evaluated in a long-term
observational study conducted in Belgium.
CARBAVANCE
The Medicines Company QIDP designation,
USA (bacterial infection)
The Medicines Company announced on 13 January 2014
that the US FDA has granted CARBAVANCE QIDP designation
for the treatment of bacterial infection. CARBAVANCE, a
fixed combination of a carbapenem (RPX 2003) and a betalactamase inhibitor (RPX 7009), is being developed for
the treatment of infections caused by multi-drug resistant
Gram negative bacteria. Phase I dose-escalation trials of
CARBAVANCE in normal subjects have been completed and
the company plans to initiate registration studies in 2014.
CB 618
Cubist CTA submission, Netherlands (bacterial
infection)
Cubist announced on 10 January 2014 that it has submitted
a CTA to the Dutch Competent Authority and Ethics
Committee, seeking approval to initiate a first-in-human
trial of CB 618. Upon approval, a first study is expected
to start in first half 2014. CB 618 is a broad-spectrum
beta-lactamase inhibitor being developed to overcome
beta-lactam antibiotic resistance.
collagenase clostridium
histolyticum
BioSpecifics Technologies clinical data (Phase
II) (lipoma)
On 8 January 2014 BioSpecifics Technologies reported topline data from a phase II trial of collagenase clostridium
histolyticum (XIAFLEX; XIAPEX) in patients with lipoma.
A total of 14 patients received collagenase clostridium
histolyticum injections in four ascending doses, ranging
16
from 0.058 to 0.44 mg. The primary efficacy endpoint
of reduction in the visible surface area of the target
lipoma, determined at six months post injection, was
met (p less than 0.0001). Patients in the highest dose
cohort (0.44 mg) had an average reduction of 67% in
the targeted lipoma visible surface area, with 75% of
the patients attaining a reduction in lipoma size of at
least 50%. No serious adverse events (AEs) or treatmentrelated serious AEs were reported during the trial. The
most common treatment-related AEs included localized
bruising, swelling and pain at injection site. This trial
further supported the safety and efficacy profile of the
drug, which was consistent with that of prior collagenase
clostridium histolyticum trials. Based on these data,
BioSpecifics Technologies plans to initiate a placebocontrolled trial to further assess the efficacy and safety
of collagenase clostridium histolyticum for the treatment
of lipoma during first half 2014.
Collagenase clostridium histolyticum, an injectable
formulation of clostridial collagenase, is available in the
USA, Canada and several European countries, including the
UK, Germany, Spain and Switzerland, for the treatment of
Dupuytren’s contracture in adults with a palpable cord. The
agent has been approved in the USA for the treatment of
Peyronie's disease and phase II evaluation is ongoing for
the treatment of frozen shoulder syndrome and edematous
fibrosclerotic panniculopathy.
CRLX 101
Cerulean clinical data (Phase II) (ovarian
cancer)
On 13 January 2014 Cerulean reported interim data from its
ongoing, single-arm, open-label phase II trial evaluating CRLX
101 for the treatment of ovarian cancer. The primary efficacy
endpoint for the trial has been met; four of 29 patients achieved
six months of progression-free survival. All 29 patients had
received between one and three lines of cytotoxic chemotherapy
prior to treatment with CRLX 101. To date, adverse events
have generally been low grade and manageable. Final data are
expected to be released during 2014.
CRLX 101 is a nanopharmaceutical, comprising the
water-insoluble alkaloid camptothecin conjugated to
cyclodextrin-polyethylene glycol (CD-PEG), for the
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dabrafenib
GlaxoSmithKline Breakthrough Therapy, USA
(BRAF V600E mutation-positive NSCLC)
On 13 January 2014 GlaxoSmithKline announced that
dabrafenib (TAFINLAR) has been granted Breakthrough
Therapy designation by the US FDA for the treatment of
metastatic BRAF V600E mutation-positive nonsmall cell
lung cancer (NSCLC) in patients who have received one
prior line of platinum-containing chemotherapy. This
designation was based on interim data from a phase II
trial of the agent in this indication.
Dabrafenib, a BRAF kinase inhibitor, has been launched
in the USA, Canada and in certain EU countries for the
treatment of unresectable or metastatic melanoma in
adult patients with a BRAF V600E mutation. The agent is
approved in Australia and Canada for this indication.
delafloxacin
20 January 2014
dexpramipexole
National Institute of Allergy and Infectious
Diseases, Knopp trial planned (Phase II), USA
(hypereosinophilic syndrome)
Knopp announced on 8 January 2014 that it has signed
a Cooperative Research and Development Agreement
(CRADA) with the National Institute of Allergy and
Infectious Diseases, part of the National Institutes of
Health (NIH; USA), to conduct a proof-of-concept phase II
trial of dexpramipexole in patients with hypereosinophilic
syndrome (HES) receiving corticosteroids. Enrollment in
this 24-week, open-label trial is planned to initiate in first
quarter 2014 in the USA. The main objective of the trial
is to evaluate the efficacy of dexpramipexole in reducing
long-term and acute corticosteroid treatment in HES
patients while maintaining or reducing eosinophil count.
Dexpramipexole, an optical enantiomer of the selective
dopamine D2/D3 receptor agonist pramipexole, has
been evaluated in a phase III trial in patients with
amyotrophic lateral sclerosis; however, development in
this indication was discontinued in January 2013. In this
trial, dexpramipexole reduced blood eosiniphil counts by
approximately 70% in patients with amyotrophic lateral
sclerosis.
DM 199
DiaMedica clinical data (Phase I) (diabetes)
Melinta phase change III, USA (gonorrhea)
On 9 January 2014 Melinta announced that it has initiated
a registration phase III trial, designated PROCEEDING,
comparing the safety and efficacy of a single oral dose
of delafloxacin with a single intramuscular injection
of ceftriaxone for the treatment of uncomplicated
gonorrhea. Melinta is developing delafloxacin, an acidic
fluoroquinolone, for the treatment of bacterial infections,
including bacterial skin and skin structure infections
(ABSSSI), pneumonia and intra-abdominal infections. A
phase III trial (PROCEED) evaluating the agent for the
treatment of ABSSSI caused by Gram positive (including
MRSA) and Gram negative bacteria is ongoing.
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On 9 January 2014 DiaMedica announced results from a
16-day, phase I multiple ascending dose (MAD) trial of DM
199 in 18 healthy volunteers. The trial has been completed
and the primary endpoints of safety and tolerability were
met. DM 199 showed a favorable pharmacokinetic profile
supporting the potential for weekly dosing and was well
tolerated at all three dose levels. Dosing of the first type
II diabetic patients in the one-month phase II trial has
been initiated. DM 199, a recombinant protein and a next
generation form of DiaMedica's DM 99 (a recombinant
version of an undisclosed generic biologic drug which has
been used for several years), is being developed for the
treatment of type I and type II diabetes.
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treatment of cancer. CRLX 101, which inhibits both
topoisomerase I and hypoxia inducible factor-1 alpha, is
selectively targeted to tumors through leaky vasculature,
whilst showing low systemic distribution. Phase II
evaluation is also being conducted for the treatment of
gastric cancer, small cell lung cancer and nonsmall cell
lung cancer (NSCLC). A phase I/II trial is also ongoing in
patients with renal cell carcinoma.
20 January 2014
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DP b99
D-Pharm phase change II, Europe
(pancreatitis)
D-Pharm announced on 14 January 2014 that it has initiated
enrollment into a multicenter, double-blind, placebocontrolled phase II trial evaluating DP b99 for the treatment
of acute pancreatitis in approximately 30 patients. Followup will involve clinical assessment scales, monitoring of
inflammatory biomarkers and abdominal imaging.
Neurovance is developing EB 1020, a triple monoamine
reuptake inhibitor acting on norepinephrine, dopamine
and serotonin (5-HT), for the oral treatment of ADHD.
EDP 788
Enanta phase change I, USA
(bacterial infection)
DP b99, a membrane-activated divalent metal ion
chelating agent derived from BAPTA (a calcium-specific
polyamino carboxylic acid), is being developed for the
treatment of acute stroke, traumatic brain injury, malaria
and trypanosomiasis, as well as for the prophylactic
treatment of neurological damage associated with coronary
artery bypass graft. A phase II trial in patients with acute
ischemic stroke has been conducted.
On 13 January 2014 Enanta announced that it has initiated
a randomized, double-blind, placebo-controlled phase
I trial to evaluate the safety and pharmacokinetics of a
single oral dose of EDP 788 in up to 64 healthy subjects.
EDP 788, a bicyclolide antibiotic, is a prodrug of EDP 322
being developed for the treatment of infections caused
by meticillin-resistant Staphylococcus aureus (MRSA),
vancomycin-resistant Enterococcus and drug-resistant
streptococci. The bicyclolides are a family of macrolide
antibiotics created by Enanta. EDP 788 is being developed
in both intravenous and oral formulations.
EB 1020
ENMD 2076
Neurovance clinical data (Phase II)
(attention deficit disorder)
EntreMed CTA submission, China
(ovarian cancer)
Neurovance on 9 January 2014 reported interim data from
a pilot phase IIa trial of a sustained-release formulation
of EB 1020 (EB 1020 SR) in adult patients with attention
deficit hyperactivity disorder (ADHD). The primary
outcome measure of change in ADHD symptoms at week
4 from baseline was statistically significant (p less than
0.0001) after treatment with EB 1020 SR. There was a 21.5
point improvement in the ADHD symptoms at week 4 as
measured by the ADHD Rating Scale IV (ADHD-RS-IV) with
80% of the peak benefit observed by the second week of
treatment. The level of reduction in ADHD symptoms with
EB 1020 SR was comparable to that observed in other adult
ADHD trials investigating standard stimulant medications
under similar trial conditions. A responder analysis by the
Clinical Global Impression of Improvement (CGI-I) and the
ADHD-RS scales showed that 72% of all patients met the
responder definition by week 4. EB 1020 SR was safe and
well tolerated and patients reported mild and transient
adverse events. Neurovance expects to release complete
data from this trial by end first quarter 2014.
On 13 January 2014 EntreMed announced that it has
submitted a CTA to China’s Food and Drug Administration
seeking approval to initiate a phase II trial evaluating
ENMD 2076 for the treatment of advanced ovarian clear
cell carcinoma; this trial is ongoing in Canada and the
USA. EntreMed is developing ENMD 2076, an angiogenesis
inhibitor and dual-acting aurora A and tyrosine kinase
inhibitor, for the oral treatment of cancer. Phase II
evaluation is ongoing in North America for the treatment
of breast cancer and soft tissue sarcoma.
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GOVX B11
GeoVax clinical data (Phase I)
(HIV infection)
On 13 January 2014 GeoVax reported interim data from an
open-label, treatment-interruption phase I trial assessing
the safety and immunogenicity of GOVX B11 in nine
HIV-infected patients who commenced drug treatment
GOVX B11, a vaccine for the prevention and treatment of
clade B HIV infection, employs a prime-boost approach:
a DNA priming dose is followed by the delivery of a
recombinant modified vaccinia Ankara (rMVA) booster.
Both components of GOVX B11 express the HIV proteins
Gag, Pol and Env and produce virus-like particles; the
vaccine is designed to stimulate anti-HIV T-cell and antiHIV antibody immune responses. A phase II trial of the
vaccine in the prevention of HIV infection in the USA and
Peru has been completed.
LBR 101
Labrys phase change II, USA (chronic and
high frequency episodic migraine)
On 8 January 2014 Labrys announced that patient
enrollment has been initiated in two separate phase
IIb trials of LBR 101 (formerly RN 307), a recombinant,
humanized monoclonal antibody targeting calcitonin generelated peptide, for the prevention of chronic and high
frequency episodic migraine. In both trials, patients will
receive placebo or a low-dose or high-dose treatment with
subcutaneous LBR 101 once monthly for three months. In
the chronic migraine trial, approximately 225 patients are
expected to be enrolled and the primary efficacy endpoint
will be the mean change from baseline in the number of
hours with headache after 12 weeks of treatment. In the
episodic migraine trial, an estimated 270 patients will
be enrolled and the primary efficacy endpoint will be the
mean change from baseline in the number of migraine days
after 12 weeks of treatment. Top-line data from these trials
are expected in late 2014 or early 2015.
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20 January 2014
NKTR 171
Nektar phase change I, USA
Nektar announced on 14 January 2014 that dosing has
begun in a single-ascending dose phase I trial evaluating
the safety, tolerability and pharmacokinetics of NKTR 171
in up to 50 healthy volunteers. NKTR 171 is a sodium
channel blocker being developed for the treatment of
neuropathic pain.
ornithine phenylacetate
Ocera phase change II, Canada, USA (hepatic
encephalopathy)
On 8 January 2014 Ocera announced that it has initiated
enrollment into its phase IIb trial, designated STOP-HE,
comparing the safety, efficacy and pharmacokinetics
of ornithine phenylacetate (OCR 002) plus standard
of care with standard of care alone for the treatment
of acute hepatic encephalopathy (HE) in hospitalized
patients with liver cirrhosis. The company aims to enroll
approximately 200 participants and will assess time to
achievement of meaningful improvement in HE symptoms.
The study is expected to complete in early 2015. Ornithine
phenylacetate, an ammonia scavenger, is being developed
for the treatment of hyperammonemia and HE in patients
with advanced liver cirrhosis and acute liver failure. Phase
II evaluation of the agent is ongoing in patients with
acute liver injury, liver cirrhosis and upper gastrointestinal
bleeding.
pracinostat
MEI Pharma starts phase II trial in
refractory MDS
On 14 January 2014 MEI Pharma announced that it has
initiated patient dosing in an open-label, two-stage phase II
trial evaluating pracinostat for the treatment of patients with
myelodysplastic syndrome (MDS) who either failed to respond
or maintain a response to a hypomethylating agent (HMA)
alone. The primary objective of this trial is to determine if the
addition of pracinostat to azacitidine or decitabine therapy
can improve clinical responses or rescue previous responses
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within 18 months of seroconversion and exhibited stablycontrolled virus for six months. GOVX B11 had a good
safety profile, with no patients requiring reinstatement of
drug therapy during the treatment-interruption part of the
trial. The agent elicited enhanced CD8+ T cells in eight
patients and enhanced CD4+ T cell and antibody responses
in four patients during vaccination; a trend towards
enhanced viral control was observed in patients with the
best CD4+ and CD8+ T cell responses. Expanded antibody
and T cell responses associated with re-emergent HIV were
demonstrated in preliminary analyses of the first seven
patients to undergo treatment interruption.
20 January 2014
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achieved with a HMA alone. The primary endpoint of clinical
improvement rate will be defined by the proportion of patients
with complete remission, partial remission and hematologic
improvement. Secondary endpoints include overall response
rate, complete remission rate, hematologic improvement
rate, duration of response, progression-free survival, time to
progression and overall survival. The company aims to enroll
up to 76 patients. Preliminary data are expected to be released
in December 2014.
Pracinostat, an oral inhibitor of histone deacetylase
(HDAC) 1, 2 and 4, is being developed for the treatment
of solid tumors and hematological cancers. A phase II trial
evaluating pacrinostat in combination with azacitidine
for the treatment of MDS is ongoing. Phase II evaluation
of pracinostat in combination with azacitide for the
treatment of elderly patients with newly diagnosed acute
myeloid leukemia is also ongoing. Data from these trials
are expected to be released by December 2014.
PRO 140
CytoDyn provides update on development
CytoDyn announced on 7 January 2014 that it has received
approval from the US FDA to start screening patients with
human immunodeficiency virus type 1 (HIV-1) infection in
a phase IIb trial of PRO 140 as an adjunct to antiretroviral
therapy. Patients with viral rebound and documented poor
adherence to prior antiretroviral regimens will receive a
subcutaneous injection of PRO 140, or placebo, once a
week for 24 weeks in combination with oral antiretroviral
agents. The trial will evaluate antiviral activity, as well as
tolerability and patient adherence. CytoDyn is developing
PRO 140, a humanized monoclonal antibody targeting HIV
co-receptor CCR5, as a potential anti-HIV agent.
PRT 201, a long acting human recombinant elastase,
is being developed to improve both the immediate and
long-term success of hemodialysis access, bypass graft and
angioplasty procedures. The agent can be applied topically
to exposed vessels during surgery, or injected through
angioplasty catheters. PRT 201 has been evaluated in
a phase II trial in patients with chronic kidney disease
undergoing surgery for arteriovenous fistula creation in
preparation for hemodialysis. A phase I trial of PRT 201
as a treatment for patients with symptomatic peripheral
artery disease is ongoing.
PXVX 0200
PaxVax clinical data (Phase III) (cholera)
PaxVax on 9 January 2014 announced interim data from
an ongoing phase III trial to assess the protection offered
by a single PXVX 0200 dose against Vibrio cholerae at
ten days and 90 days after vaccination. PXVX 0200 was
well tolerated. At ten days post vaccination, two of 35
participants in the PXVX 0200 group had moderate-tosevere diarrhea compared to 20 of 33 participants in the
placebo group.
PaxVax is developing PXVX 0200, a single dose, oral, live
attenuated vaccine, for the prevention of cholera. The
vaccine, originally developed by Berna (now Crucell) in
collaboration with the University of Maryland (USA), was
first launched in Switzerland in May 1994 and subsequently
made available in five other countries, including Canada,
under the trade names OROCHOL and MUTACOL BERNA;
however, production of the vaccine ceased in 2004 owing
to business considerations.
RX 3117
PRT 201
Rexahn phase change I, USA (solid tumor)
Proteon Orphan Drug, EU (prevention of
arteriovenous access dysfunction)
On 8 January 2014 Rexahn announced that it has initiated
a multicenter, dose-escalation phase Ib trial to evaluate the
safety, tolerability, dose-limiting toxicities and maximum
tolerated dose of oral RX 3117 in patients with solid tumors
in the USA. Up to 30 patients will receive RX 3117 thrice
weekly for three weeks followed by one week off treatment
for up to eight cycles. The secondary endpoints will be
On 8 January 2014 Proteon announced that PRT 201
has been granted Orphan Drug designation in the EU for
the prevention of arteriovenous access dysfunction in
hemodialysis patients.
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samatasvir & simeprevir
Idenix clinical data (Phase II) (hepatitis C)
On 13 January 2014 Idenix announced interim data
from an ongoing, 12-week, phase II trial (HELIX-1) of a
combination of samatasvir (IDX 719), a hepatitis C virus
(HCV) NS5A inhibitor, and simeprevir, a HCV protease
NS3/4A inhibitor, in treatment-naive, non-cirrhotic
patients with genotype 1b or 4 HCV infection. The trial
consists of two parts. In part A, 63 patients received
once-daily samatasvir (50, 100 or 150 mg) in combination
with simeprevir (150 mg) plus ribavirin for 12 weeks. In
part B, exploratory cohorts of patients were added to
evaluate the safety and antiviral activity of simeprevir
and ribavirin in combination with samatasvir 25 mg in
patients with genotype 1b HCV infection and samatasvir
100 mg in patients with genotype 6 HCV infection. Results
from part A showed that the combination regimen was
well tolerated. No treatment-related serious adverse
events were reported. Fatigue, pruritus, anemia, nausea
and insomnia were the most frequently reported adverse
events. After four weeks of treatment, rapid virologic
response was seen in 20 of 20 patients, 20 of 21 patients
and 18 of 19 patients in the samatasvir 50, 100 and 150
mg groups, respectively; sustained virologic response was
seen in 17, 16 and ten patients in the samatasvir 50, 100
and 150 mg groups, respectively. At the end of 12-week
treatment period, response was seen in 18, 19 and 11
patients in the samatasvir 50, 100 and 150 mg groups,
respectively. Samatasvir 50 mg was selected for evaluation
in an ongoing phase II trial designated HELIX-2.
Simeprevir is available in Japan, the USA and Canada for use
in combination with PEGylated interferon and ribavirin for
the treatment of genotype 1 chronic HCV infection, and is
pending approval in the EU for this indication. The HELIX-2
phase II trial is evaluating samatasvir in combination with
simeprevir and TMC 647055 in treatment-naive or relapsed
patients with HCV genotype 1 infections.
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20 January 2014
SDP 051
Adheron clinical data (Phase I)
On 8 January 2014 Adheron reported results from a placebocontrolled phase I trial of SDP 051 in healthy volunteers.
SDP 051 was safe and well tolerated at doses up to 10
mg/kg per day with no significant side effects. SDP 051,
a humanized monoclonal antibody targeting cadherin-11,
is being developed for the treatment of various diseases,
including rheumatoid arthritis and fibrosis. Adheron
expects to start a phase II trial to evaluate once monthly
dosing of the antibody in 2015.
selective inhibitors of nuclear
export, Karyopharm
Karyopharm provides update on development
Karyopharm announced on 8 January 2014 that it has been
awarded a grant from the National Multiple Sclerosis Society
(USA) to evaluate its selective inhibitors of nuclear export
(SINE) compounds in the treatment of multiple sclerosis.
The SINE compounds inhibit exportin-1 (XPO1, also known
as CRM1), a nuclear export protein that mediates the export
of approximately 285 different cargo proteins, including
the vast majority of tumor suppressor proteins. Discovery
stage research is under way.
SGK1 inhibitors, Visionary
Pharmaceuticals/BioBlocks
Visionary Pharmaceuticals and BioBlocks sign
collaboration agreement
Visionary Pharmaceuticals and BioBlocks announced on
8 January 2014 that they have signed a collaboration
agreement for the development of small molecule
inhibitors of serum and glucocorticoid-regulated kinase
1 (SGK1), a serine/threonine protein kinase that plays
an important role in the cellular stress response and ion
channel activation, for the treatment of cancers, including
triple-negative breast cancer. The inhibitors are being
identified using BioBlocks' Leap-to-Lead small molecule
lead discovery platform and Visionary Pharmaceuticals'
BindingSIGHTS technology platform, and target the
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R &D FO C US dr ugne w s
to assess the pharmacokinetic profile and preliminary
antitumor effects of RX 3117. Rexahn expects to complete
patient enrollment in this trial by end 2014 and to release
data in first half 2015. RX 3117, a cytotoxic antimetabolite
nucleoside, is being developed for the treatment of solid
tumors, including colon, lung and pancreatic cancers.
20 January 2014
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abnormal glycosylation and metabolite production that
occur in tumor cells. Discovery stage research is under way.
TG 4010
Transgene clinical data (Phase II/III) (NSCLC)
On 8 January 2014 Transgene announced top-line
preliminary results from the phase IIb part of a phase IIb/
III trial (TIME) evaluating the safety and efficacy of TG 4010
(MVA-MUC1-IL2) in combination with chemotherapy versus
chemotherapy alone in the first-line treatment of MUC-1
positive patients with advanced nonsmall cell lung cancer
(NSCLC). 210 patients were enrolled in total in the phase IIb
part of the trial and the primary objective was to determine
the patient's triple-positive activated lymphocytes (TrPAL)
level using an upper limit of normal (ULN) threshold
based on TrPAL levels in healthy individuals. Results
showed that the trial did not meet its primary endpoint
when the ULN threshold was used. However, a pre-planned
progression-free survival (PFS) analysis using a quartile
approach (refined threshold) showed an improvement in
PFS in the 75% of TG 4010-treated patients with lower
TrPAL levels and no improvement in PFS in the 25% of TG
4010-treated patients with higher TrPAL levels. TG 4010
was well tolerated and the nature and incidence of adverse
events were consistent with the previous phase II trials.
Transgene plans to advance the trial into the phase III part,
in which the patient population will be selected based on
TrPAL levels. Detailed results from this trial are expected in
2014. TG 4010, a MUC-1 targeted immunotherapy, is being
developed as an adjunct to chemotherapy for the treatment
of NSCLC.
TRV 027
Trevena initiates phase IIb trial
Trevena reported on 9 January 2014 that it has initiated
a randomized, active-controlled, double-blind, multicenter
phase IIb trial (BLAST-AHF) of TRV 027 in patients with
acute heart failure. About 500 patients will receive TRV
027 at doses of 1.0, 5.0 or 25 mg/h, or placebo, plus
standard heart failure therapy for a minimum of 48 h
and up to 96 h. The primary objective of this trial is to
evaluate the effects of the three dose levels of the agent
22
on mortality, worsening heart failure, hospital readmission
rate, dyspnea, and length of hospital stay. TRV 027, a
beta-arrestin biased angiotensin II type 1 receptor (AT1R)
ligand, is being developed as a titratable iv agent for the
treatment of acute decompensated heart failure.
vaccine, H1N1 influenza, Vaxart
Vaxart clinical data (Phase I) (influenza)
On 9 January 2014 Vaxart reported data from a phase Ib trial
evaluating the safety and immunogenicity of its oral vaccine
for seasonal influenza. A total of 88% of the participants
in this trial had anti-hemagglutinin antibody responses,
with 45% and 55% of them showing four-fold increases in
neutralizing antibodies in the hemagglutination inhibition
assay and microneutralization assay, respectively.
Vaxart’s vaccine is being developed for protection against
H1N1 influenza (swine flu). It comprises a non-replicating
chimeric adenovirus-5 vector, which has been engineered
to express H1N1 influenza hemagglutinin, and a Toll-like
receptor 3 (TLR3) ligand vaccine adjuvant.
VX 135
Vertex reports clinical data (Phase II)
(hepatitis C)
On 9 January 2014 Vertex announced data from the first
two cohorts of an open-label phase IIa trial of VX 135
in combination with Bristol-Myers Squibb’s daclatasvir in
non-cirrhotic, treatment-naive patients with genotype 1
hepatitis C virus (HCV) infection. Patients received 100 or
200 mg of VX 135 in combination with 60 mg daclatasvir
once daily for 12 weeks. In an intent-to-treat analysis,
58% of the patients in the 200 mg dose cohort and 73% of
the patients in the 100 mg dose cohort had undetectable
HCV RNA after four weeks of treatment. The sustained viral
response rate four weeks after the completion of treatment
(SVR4) was 83% and 73% in the 200 and 100 mg dose
cohorts, respectively. In the 200 mg dose cohort (n=12),
one patient who discontinued treatment after the first dose
due to a serious adverse event of vomiting/nausea did not
achieve SVR4. The remaining 11 patients completed 12
weeks of treatment, and 91% achieved SVR4. In the 100 mg
Sourced from IMS LifeCycle R&D Focus.
© 2014 IMS Health Incorporated or its affiliates. All rights reserved.
VX 135, an oral uridine nucleotide analogue prodrug, is
undergoing phase II evaluation in combination with
ribavirin in treatment-naive patients with HCV infection. In
April 2013, Vertex and Bristol-Myers Squibb have entered
into a non-exclusive agreement to conduct two phase II
trials of VX 135 in combination with daclatasvir for the
treatment of HCV infections.
Immunomedics phase change III
(pancreatic cancer)
WTX 101
Wilson Therapeutics IND approved, USA
(Wilson disease)
Wilson Therapeutics reported on 13 January 2014 that the
US FDA has accepted an IND application to begin a phase I
trial of WTX 101 in the treatment of Wilson's disease. WTX
101 is a bis-choline formulation of tetrathiomolybdate
(TTM), a decoppering agent that has shown evidence
of an ability to stabilize neurological function and
reduce the risk of neurological deterioration in Wilson's
disease patients with neurological disease. WTX 101
has been tested in clinical trials in cancer patients; the
Sourced from IMS LifeCycle R&D Focus.
© 2014 IMS Health Incorporated or its affiliates. All rights reserved.
yttrium Y 90 clivatuzumab
tetraxetan
On 9 January 2014 Immunomedics announced that it
has initiated a randomized, double-blind phase III trial,
designated PANCRIT-1, evaluating the safety and efficacy of
yttrium Y 90 clivatuzumab tetraxetan, in combination with
low-dose gemcitabine and best supportive care, in patients
with metastatic pancreatic cancer who have received at
least two prior therapies (of which one must have contained
gemcitabine). The company aims to enroll approximately
440 participants who will be randomized 2 to 1 to the
treatment arm of three doses of yttrium Y 90 clivatuzumab
tetraxetan plus four doses of gemcitabine at 200 mg/m2 per
cycle or placebo plus low-dose gemcitabine. Treatments will
be administered during the first four weeks of each sevenweek cycle, and repeated up to a maximum of six cycles. The
primary endpoint is overall survival. Enrollment is expected
to be completed during first half 2015. Immunomedics
is developing yttrium Y 90 clivatuzumab tetraxetan, a
humanized monoclonal antibody targeted against an epitope
in the MUC1 antigen expressed in most pancreatic cancers.
23
20 January 2014
agent showed a favorable safety and tolerability profile,
effectively reducing copper levels when administered once
daily. WTX 101 has been granted Orphan Drug designation
for treating Wilson's disease in the EU and the USA.
R &D FO C US dr ugne w s
dose cohort (n=11), two patients had viral breakthrough.
One patient in each dose cohort relapsed during the followup period. Overall, the adverse events were mild in severity
across the trial. The most common adverse events reported
in at least 10% of patients included fatigue, headache and
nausea. Based on this data, Vertex and Bristol-Myers Squibb
plan to enroll additional patients with both genotype 1
and 3 HCV infection.
R&D FO C US dr ugne w s
24
Newly Reported Drugs in R&D Focus
Sourced from IMS LifeCycle R&D Focus.
© 2014 IMS Health Incorporated or its affiliates. All rights reserved.
Company
Product
Therapeutic Class
Indication
Phase
AC Immune
Adheron
Adimab
Anaconda
ACI 35
SDP 051
MAbs, cancer, Adimab/FivePrime
AP 611074
J7C; N7D9
M1C; V3X
L1X3
J5B9
Phase I
Phase I
Discovery
Phase I/II
AnaptysBio
ANB 020
L4X
Anavex Life Sciences
Biogen Idec
BioMarin
BiOncoTech
BiOncoTech
Brabant
Circadian Technologies
Cubist
CytomX
ANAVEX 2-73 + donepezil
SNS 062
BMN 270
BO 011
BO 110
BRABAFEN
OPT 302
CB 618
PROBODY-drug conjugates, cancer, CytomX/ImmunoGen
microRNAs, neurodegenerative diseases, InteRNA/
UCB/Bonn University
cancer therapy, ImmTAC, MedImmune/Immunocore
phosphoinositide-dependent kinase-1 inhibitors, Sunesis
mPGES-1 inhibitors, NovaSAID/Cadila
MAb, PDGFR-beta, Regeneron/Bayer
ANAVEX 2-73 + donepezil
gene therapy, hemoglobinopathies, Sangamo
BioSciences/Biogen Idec
niche activators, TGF-beta 1, Scholar Rock/Johnson &
Johnson
OPT 302
phosphoinositide-dependent kinase-1 inhibitors, Sunesis
SNS 062
N7D9
L1X4
B6C
L1X3
L1X9
N3A; V7A
S1P
J1X9
L1X3
Alzheimer disease
fibrosis; rheumatoid arthritis
cancer
genital warts
allergic rhinitis; allergy; asthma; COPD;
dermatitis; fibrosis
Alzheimer disease
hematological cancer
hemophilia
cancer
cancer
epilepsy
wet AMD
bacterial infection
cancer
Preclinical
Preclinical
Preclinical
Preclinical
Preclinical
Clinicals
Preclinical
Preclinical
Discovery
N7X
neurodegeneration
Discovery
L1X3
L1X4
L4X; N2B
S1P
N7D9
cancer
cancer
inflammation; pain
AMD
Alzheimer disease
Discovery
Discovery
Discovery
Preclinical
Preclinical
B6C
sickle cell anemia; thalassemia
Discovery
L4X
autoimmune disease; cancer
Discovery
S1P
L1X4
L1X4
wet AMD
cancer
hematological cancer
Preclinical
Discovery
Preclinical
Visionary
Pharmaceuticals
SGK1 inhibitors, Visionary Pharmaceuticals/BioBlocks
L1X4
cancer
Discovery
Wilson Therapeutics
WTX 101
N7X; V7A
Wilson disease
Preclinical
Xiber Science
Xib 13
D3A9; L4X
burn; transplant rejection
Preclinical
InteRNA
MedImmune
Millennium
NovaSAID
Regeneron
Roskamp Institute
Sangamo BioSciences
Scholar Rock
Selexis
Sunesis
Sunesis
Preclinical
20 January 2014
Sourced from IMS LifeCycle R&D Focus.
© 2014 IMS Health Incorporated or its affiliates. All rights reserved.
Product Phase Changes Reported in R&D Focus
Company
Product
Therapeutic Class*
Indication
New Phase
Region of Phase Change
Highest Phase
AstraZeneca
dapagliflozin
A10X9
diabetes
Registered
USA
Marketed
Novartis
indacaterol +
R3G4
glycopyrronium bromide
COPD
Registered
Canada
Marketed
GlaxoSmithKline
umeclidinium bromide +
R3G4
vilanterol
COPD
Registered
Canada
Registered
Daiichi Sankyo
edoxaban
B1F
stroke; thrombosis
Pre-registration
USA
Marketed
Merck & Co
lambrolizumab
L1X3
melanoma
Pre-registration
USA
Pre-registration
Clarus
REXTORO
G3B; V7A
hormone deficiency
Pre-registration
USA
Pre-registration
Baxter
RIXUBIS
B2D2
hemophilia
Pre-registration
Japan
Marketed
Boehringer Ingelheim
tiotropium bromide
R3G3
asthma
Pre-registration
Japan
Marketed
Melinta
delafloxacin
J1G
gonorrhea
Phase III
USA
Phase III
Immunomedics
yttrium Y 90
L1X3; V3C
clivatuzumab tetraxetan
pancreatic cancer
Phase III
Canada; Europe; Israel;
USA
Phase III
Alios
ALS 8176
J5B5
respiratory syncytial
virus
Phase II
USA
Phase II
D-Pharm
DP b99
A16A; N7X; P1D1; P1G
pancreatitis
Phase II
Europe
Phase III
Labrys
LBR 101
N2C9
migraine
Phase II
USA
Phase II
Ocera
ornithine phenylacetate
A16A
hepatic
encephalopathy
Phase II
Canada; USA
Phase II
AC Immune
ACI 35
J7C; N7D9
Alzheimer disease
Phase I
Europe
Phase I
Enanta
EDP 788
J1F
bacterial infection
Phase I
USA
Phase I
Nektar
NKTR 171
N7X
neuropathic pain
Phase I
USA
Phase I
Rexahn
RX 3117
L1B
solid tumor
Phase I
USA
Phase I
BioMarin
BMN 270
B6C
hemophilia
Preclinical
USA
Preclinical
* A change in phase may not apply to all therapeutic classes
25
R&D FO C US dr ugne w s
20 January 2014

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