Scaling up screening , diagnostic and treatments for people living

Scaling up screening , diagnostic and
treatments for people living with
HCV in 2014?
Isabelle Andrieux-Meyer, MD
Médecins Sans Frontières
Access Campaign
WHO Technical Briefing Seminar
November 6th,2014
[email protected]
Scaling up screening and diagnostics for people living
with HCV
-
Access to reliable epidemiological data
Access to HCV screening & diagnostic
Who is the most at risk?
Access to HCV treatments in 2014 in LMIC?
Global Prevalence of Hepatitis C
New HCV /HIV epidemiological data. Center
for Disease Analysis 2013
Access to HCV screening: a game
changer
• Globally, 59% of the world’s population has no access to hepatitis C
diagnosis. Dx using serology is available in 53% of lower middle
income countries, and 11% of low income countries ( WHA report
2010).
• HCV Scan (EY laboratories) sensibility: 100%, specificity: 93.7% (
WHO 2001) or HCV Spot (MP Medicals) : average price 1-4 eur per
test
• MSF recommends OraQuick (Orasure, USA): Best and most up to
date performance but 10-12x more expensive than other RDTs.( 14
euros/test) (sensibility: 99.2%, specificity: 99.8% ( Lee 2010) Can be done
on whole blood (e.g finger prick) or oral fluid. ( MSF HCV landscape analysis 2014)
• Limited evidence on the accuracy of HCV RDTs in HIV/HCV coinfection. (
Shivkumar Ann Intern Med 2012)( Smith J Itl Dis 2011)
Primary prevention /HCV transmission
• Blood to blood contact.
• Transmission in developed countries:
– 90% chronic HCV infection were infected through transfusion of
unscreened blood ( Alter JAMA 1990)
– Or sharing contaminated needles or other drug injection equipment (
Villano SA, Drug and Alcohol Dependance 2009).HCV seroprevalence among drug
users ( IDU) : 60% (Nelson PK, Lancet 2011)
– Less commonly HCV is transmitted by sexual contact with an infected
person, including MSM, or birth to an infected mother.( Wandeler G CID 2013)
• In developing countries:
– the primary sources of HCV infection are unsterilized injection
equipment and infusion of inadequately screened blood and blood
product .
MSF UNITAID HIV-HCV grant
HCV public health problem, prevalence HCV –HIV co-infection
• 52.3% HCV-HIV co-infected patients in NE
India
• 67.2% in IDU in Iran
• 10.3% in Nairobi, Kenya
• 15.7% in Mozambique
• 29% in North Myanmar
• 53.3% among IDU in Ukraine
(Devi KS,I nis,2005)
( Seyed Alinaghi S, Acta Med Iran 2011)
(Muriuki BM, BMC Research notes 2013)
( Rodrigues, 2008)
( MSF OCA 2014, unpublished data)
( MSF OCB, unpublished data)
Who is the most at risk?preliminary
investigation
• India: transgender people, people using drugs (IDU),
commercial sex workers ( CSW)
• Myanmar: Migrants, IDU
• Ukraine: prisoners, complex HIV patients , MDRTB, TB
patients, men who have sex with men (MSM)
• Iran: commercial sex workers, IDU
• Mozambique &Kenya: IDU, CSW?, blood recipient,
invasive medical dental surgical procedure, tatoos,
health care workers, prisoners, mobile populations (
migrant workers, miners)
• Need to investigate patterns of transmission at country
level , collect epidemiological datas
HCV confirmation test: Detection of HCV
RNA
• HCV PCR is the most common method to detect viral RNA. It is also used
to quantify the virus for treatment monitoring purpose. Usually: Abbott,
Roche, Siemens quantitative VL.
• HCV PCR is hardly accessible and costs >=100 USD per test.
• We need affordable :
– POC HCV Viral load : pipeline Wave 80, Alere, Cepheid, IQuum, Daktari.
– Flexible PCR platforms ( Multitest: HBV-HIV-HCV) like Sacace generic open
platform test, or Qiagen. ( MSF HCV landscape analysis 2014)
Prohibitive Costs: Georgia: serology+ PCR RNA HCV+ genotype=USD135
Nigeria, India: package=500 USD
3. Genotyping & Fibrosis evaluation
• The required length of peg-IFN-ribavirin treatment, or oral
treatments, and the expected outcome from treatment, is
dependent on the HCV genotype.
• Tests, using a range of different technologies:
– Abbott , Roche, Siemens tests
– Sacace: generic open platform test (real time PCR)
– Pipeline point-of-care test: Wave80
New oral drugs will allow for simplification , if we have access
to pan-genotypic treatment then genotyping may not be
needed
Liver fibrosis can be assessed at field level using Transient
elastography: Fibroscan, or serum biomarkers like APRI( Lin ZH.
Hepatol 2011) ( WHO HCV Guidelines 2014).
Treatment should be simple, highly effective, pan-genotypic, potent, at
affordable cost, easy to take ( MSF HCV landscape analysis 2014)
Drug /combination
Overall Results
Sofosbuvir (SOF)
ribavirin ( RBV)
GT2, phase III 12weeks SVR12: 93%
SOF RBV
GT3 , phase III 24 weeks SVR12: 85%
SOF RBV
GT1 phase III 24 weeks SVR12: 76%
Peg-IFN +SOF+RBV
GT1 phase III 12 weeks SVR12: 90%
SOF + LDV(ledipasvir)
GT1 phase III 12 weeks SVR12 97.7%
SOF+LDV
GT1 phase III 8 weeks SVR12: 94%
SOF+ LDV+GS 9669
GT1 phase II 6 weeks SVR12 95% ( N=20)
SOF+LDV+GS 9451
GT1 phase II 6 weeks SVR12 100% ( N= 20)
Drug/combination
Overall
results EASL 2014
3. Update
Sofosbuvir+ GS 5816
12 weeks
SOF 400mg+GS5816 100mg
N= 77
GT1: SVR12 28/28 :100%
GT2: 10/10 : 100%
GT3: 25/27 : 93%
GT4: 7/7
GT5: -Gt6: 5/5
(Everson EASL 2014)
Sofosbuvir+ledipasvir
HIV+HCV, N=50
SOF 400mg+GS5816 25mg
N=77
GT1 : SVR12: 26/27 : 96%
GT2: 10/11 : 91%
GT3: 25/27: 93%
GT4: 6/7
GT5: 1/1
Gt6: 4/4
GT1 no ART: SVR12: 10/10
GT1 on ART: SVR4: 21/21
( Osinusi A.EASL 2014)
Sofosbuvir ledipasvir
400/90 mg
Electron 2 ( EASL 2014 oral6)
GT3 12 weeks SOF+LDP+RBV : SVR12: 19/19 ( 100%)
GT3 12 weeks SOF+LDP: SVR12: 16/26 ( 64%)
Sofosbuvir ledipasvir
Electron 2 ( EASL 2014 oral6)
GT1 prior failure peg IFN +RBV: SOF+LDP+RBV: SVR12: 19/19
GT1 decompensated cirrhosis or Child B: SOF+LDP no RBV:
SVR12: 13/20 well tolerated
LDV/SOF STR
Study*
regimen
ION-1(n=865)
GT1 naive
16% cirrhosis
LDV/SOF STR
12 weeks
ION-2 (n=440)
GT1 experienced
20% cirrhosis
LDV/SOF STR 12 weeks
ION-3 (n=647)
GT1 naive no
cirrhosis
LDV/SOF 8 weeks
SVR12
99%
94%
94%
94%
Adding ribavirin did not increase SVR12
LDV/SOF STR was safe and well tolerated
Addition of RBV contributed to higher incidence of AE and lab abnormalities, including
mean hemoglobin levles over time.
ION-1 and 2: 24 weeks results are similar to 12 weeks results
ION-3: 8 weeks and 12 weeks results are similar
The best components should be studied in combination and selected for market impact (MSF
HCV landscape analysis 2014)
Drug /combination
Overall results
SOF+simeprevir
SOF+simeprevir + RBV
GT 1phase II 12 weeks SVR12 100% (n=14)
SVR12 100% (n=12
SOF+Daclatasvir (DCV) GT1 phase II 12 or 24 weeks SVR12 100% ( n=14)
SOF+DCV+RBV
SVR12 95% ( n=15)
SOF +DCV
GT1 Naïve SVR12 98%
GT1 Experienced SVR12 98%
SOF+DCV
GT2 SVR12 92% (n=26)
SOF+DCV
GT3 SVR12 89% (n=18)
DCV+ asunepravir+
BMS 791325
GT1 phase II -12 or 24 weeks SVR12 94%
DCV 30mg+
simeprevir (SMV)+/RBV
GT1 SVR12= 75-85% in treatment naïve
SVR 12 = 65-95% in prior null responders
ABT 450/ +-ABT 267+ABT333+-RBV
phase III, GT1, tt naïve, 12 weeks:
3 DAA+ RBV : SVR12: 99.5%,3 DAA: SVR12: 99%
Merck pipeline
Phase 1b
Phase 2
Phase 3
Reg review
MK-3682 ( NS5b PI)
Ex Idenix 21437
MK-1894 ( NS5a I)
Samatasvir
MK-5172 ( NS3/4
PI)
MK-8742 ( NS5a I)
Vamiprevir ( Japan)
(NS3/4Pi)
MK-8408 (NS5a I)
Daclatasvir: European Commission
Approval August 2014 (1)
GT 1 or 4 no cirrhosis
Daclatasvir
(Daklinza)sofosbuvir
GT1 or 4 compensated Daclatasvir sofosbuvir
cirrhosis
12 weeks, consider prolongation to
24 weeks with prior treatment
including NS3a/4 protease inhibitor
Shortening treatment to 12 weeks
may be considered for patients
previously untreated with cirrhosis
and positive prognosis factors such
as IL28B CC genotype and /or low
baseline viral load
Consider add ribavirin with patients
with very advanced liver disease or
with negative prognosis factor such
as prior treatment experience
Daclatasvir approval (2)
GT 3 with compensated
cirrhosis and /or
treatment experienced
Daclatasvir sofosbuvir
ribavirin
24 weeks
GT4
Daklinza peginterferon
ribavirin
24 weeks daclatasvir in
combination with 24-48
weks of peginterferon
ribavirin.
Daclatasvir access issues
• Voluntary licensing program for 90 countries
has been announced last Friday
• Tiered pricing strategy
• No commitment on registration
• Concerns about market diversion
Specific drug requirements for MSF projects
• Basic regimen:
– GT1,3,4: SOF RBV , 24weeks
– GT2: SOF RBV ,12 weeks
– GT5, 6: pegifn SOF RBV 12 weeks
- Compatible with Atripla, no data/ nevirapine and lopinavir
based regimen.
• Alternatives needed for :
– Intolerants to ribavirin ( anemia)
– Advanced liver disease
Sofosbuvir ledipasvir , no need RBV, Gt1,2,3
Or Sofosbuvir daclatasvir combinations w/wo RBV (pan GT)
Sovaldi : 84 000 USD for 12 weeks USA, 56 000 euros for 12 weeks in France France,
1700 dollars in Egypt.
Gilead Access program : 60 countries belong to the lowest tiered pricing category, price
negotiations for sofosbuvir ‘s price start at 300 - 350 USD per bottle of 28 tablets 900 – 1000
USD for 12 weeks . ( Gilead PR, February 2014)
If you need to buy peginterferon: Merck: negotiate the Egyptian price: 40 USD per vial, including
ribavirin!
If you need to buy ribavirin to combine to sofosbuvir: Zydus: minimal quantity 750,000 caps,
price per caps: 0.30 USD.
COST PER PERSON, FOR 12 WEEK COURSE OF HCV DAA
Agent
Daily Dose
(mg)
Overall dose for
12wks (g)
Production cost
estimate ($/g)
Predicted cost
($)
Ribavirin
1200
101
0.34*
50**
Daclatasvir
60
5
4.0
20
Sofosbuvir
400
34
3.0
102
MK-8742
50
4
11.0
44
MK-5172
100
8
8.9
71
Ledipasvir
90
8
11.6
93
* current mid-point cost of API from 3 Chinese suppliers
**shows cost for 1200mg daily dose; $41 for 1000mg daily dose of ribavirin
Courtesy Andrew Hill. Poster LBPE12. IAC 2014.
BUNDLE OF CARE COSTS- A. HILL-
Interventions to overcome access
barriers to HCV treatment
• Access to reliable epidemiological data , investigation of the
patterns of transmission.
• Access to reliable and affordable diagnostics ( WHO pre-qualified,
rapid diagnostic tests, multi-analytic PCR platforms , Point of Care
HCV viral load).
• Access to care without discrimination, including people who use
drugs.
• Demonstration projects: performance & feasibility at large scale,
simplification, task shifting, training, including screeningprevention-harm reduction-treatment in different epidemiological
contexts.
• Free generic competition
• Goal: diagnostic –treatment package< 500 USD per cure.

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