The Interna*onal Liver Congress 2014 Robert Fieldhouse, BASELINE Lost in a sea of toupes and bow *es. Jokes about cricket??? ILC 2014 • Predominantly medics and scien*sts • Few journalists considering significance of data being presented • The ‘Vancouver’ for hepa**s • HIV and many other previous complicators is no longer a barrier to cure • Cure rates 90-‐100% with many inves*ga*onal 2/3 drug combos with/without ribavirin Background • Over the past 25 years cure rates with hepa**s C treatment have increased drama*cally • With Peg/Rib HIV associated with lower cure rate • 12 week tablet-‐based therapy becoming norm for first treatment; 24 weeks for experienced • Similar response in people with cirrhosis is now being demonstrated in some studies Access? • In the UK who will be treated first? • Transplant recipients? HIV +? Prisoners? • Some medicines are now available compassionately-‐ role for CAB to get info? • Many seangs don’t have accurate prevalence figures • Treatment as preven*on for hep C is a concept being widely debated and modelled now People who use drugs • Reports of new treatments are as effec*ve for people who are ac*vely using drugs • Unfortunately a leading UK hepatologist suggested; ‘perhaps the new drugs should be reserved for young people with good livers, who don’t take drugs. Ac*ve drug users could have Peg/Rib.’ Protest at high price of Sofosbuvir Licensed early 2014 in EU $1000 per pill in US Slightly Cheaper in Europe/UK Protest Against the exorbitant price of Gilead’s Sofosbuvir organised by INPUD. (Interna*onal network of people who use drugs) • Handed out golden gliher pils – good representa*on of PLWH • “Sovaldi, so expensive.” • First *me hepatologists had seen anything like it. • • • • Egypt and Sofosbuvir • Gilead selling sofosbuvir at 99% reduc*on on US price in Egypt • Es*mated 12 million living with HCV • Plan to treat 1 million people in next 3 years with Sofosbuvir • $900 per course • But • $500 maximum price for low-‐income countries to pay for cure and monitoring, according to MSF • MSF has also nego*ated reduced price for a few other countries-‐ Mozambique, Iran, India…. • Voluntary licenses to produce generic to a number of Indian pharma firms Barriers to Global Access of new meds • • • • • • • • Cost Poli*cal Will Improved Screening Need for educa*on for the public Need to work on doctors’ aatudes Communi*es affected Who will be best placed to deliver the treatment? What if treatment becomes 4 or 6 weeks G.Ps? community nurses? WHO and EASL launch Hepa**s Treatment Guidelines • WHO and EASL launched new guidelines. • EASL now recommend all the latest approved direct-‐ac*ng an*viral (DAA)-‐based treatment, mix and match approach-‐ a ‘live’ document to be regularly updated • First WHO guidelines to cover HCV treatment were published for low-‐ and middle-‐income countries, where most people with hepa**s C live. Cost not considered as not known at *me of wri*ng-‐ not due to be updated un*l 2016. Sofosbuvir/Ledipasvir • Sofosbuvir now studied in people with advanced liver disease (including decompensated cirrhosis and post-‐transplant recurrence), in people who previously used sofosbuvir and other DAAs, and in HIV coinfec*on. • Sofosbuvir is ac*ve against all genotypes (less in G3). • 100% SVR 12 in 50 people with HIV/HCV with 12 weeks of treatment – Could it be reduced to 8 weeks? • Ledipasvir mainly ac*ve against G1. Coformula*on of sofosbuvir and ledipasvir (400 mg/90 mg). Studies using the fixed dose combina*on at EASL 2014 included first results in people with HIV/HCV coinfec*on. GS-‐5816 • GS-‐5816 is an NS5A inhibitor that is ac*ve against genotypes 1-‐6 and produced SVR12 results >95% in a Phase 2 study with sofosbuvir (though low numbers for G 4, 5, and 6). SIMEPREVIR (JANSSEN) • To be licensed in EU next month • This is another compound studied with sofosbuvir (and historically with PEG/RIB) • At EASL 2014, final results and sub analysis from the COSMOS study were reported; • SVR 12 in 93% with mild/moderate fibrosis • Suspect it will be similarly priced to telaprevir DACLATASVIR, ASUNAPREVIR (BMS) • Daclatasvir produced best results in combina*on with sofosbuvir (in research not supported by Gilead) but another study also looked at an all-‐BMS combina*ons of daclatasvir with asunaprevir (NS3 protease inhibitor) and BMS-‐791325 (non-‐nucleoside NS5B inhibitor). • Asunaprevir is ac*ve in G1 and G4. • Phase 3 studies are underway in the US with daclatasvir and sofosbuvir for genotype 1, 2, 3 and 4 (the ALLY studies). • BMS permit compassionate use of daclatasvir with sofosbuvir. • BMS not seeking license for asuneprevir in Europe • ABT-‐450/R/ABT-‐267, ABT-‐333 (ABBVIE) The AbbVie “2D” combina*on includes ABT-‐450/ritonavir and ABT-‐267 (ombitasvir) coformulated in a once-‐daily pill (150 mg/100 mg/25 mg) • AbbVie’s “3D” combina*on includes ABT-‐333 (dasabuvir) in a 250 mg twice-‐daily dose. High SVR12 rates (>95%) were reported in genotype 1a and 1b, including people previously treated with pegylated interferon and ribavirin. • For genotype 4, ribavirin is used instead of ABT-‐333 (since it is not effec*ve against non-‐1 genotypes). The phase II PEARL study reported 100% SVR12 with ribavirin and 91% without, using 12 weeks treatment. • The TURQUOISE-‐II study using 3D + ribavirin in people with compensated cirrhosis reported impressive SVR12 rates auer 12 and 24 weeks of treatment of 92% and 96%, respec*vely. FALDAPREVIR AND DELEOBUVIR (BOEHRINGER INGELHIEM) • Although several presenta*ons included study results using faldaprevir, the associated side effects (nausea, GI) makes it difficult to know whether this drug will have advantages over other DAAs. • Deleobuvir has already had development stopped due to high side effects-‐related discon*nua*ons. • Ac*ve in genotype 1a. Studied with and without ribavirin. • May be des*ned to become the *pranavir of HCV? • “It took a lot of love to help the pa*ents get through the study.” MK-‐5172 AND MK-‐8742 (MERCK) • MK-‐5172 (NS3/4A protease inhibitor) and MK-‐8742 (NS5A inhibitor) are ac*ve against genotype 1, (with ongoing studies looking at other genotypes). • Now studied in people with compensated cirrhosis without ribavirin, prior treatment experience, and in HIV coinfec*on. A fixed dose single pill formula*on (dose 100 mg/50 mg) will be used in phase 3 studies, including in people with cirrhosis. • A small HIV/HCV coinfec*on study (n=40) in HIV posi*ve people on stable ART with high CD4 counts produced SVR4 results of 97% with ribavirin and 90% without. Future phase 3 studies with include HIV posi*ve people, including in an opiate subs*tu*on study. Conclusions • Outstanding cure rates with new meds • Docs may choose based on cost/study size/genotype/experience/ previous treatment/pa*ent choice? • Challenge will be to expand screening, improve surveillance and increase current *ny treatment rates • Will treatment for 6 or 4 weeks be effec*ve? • People with hep C don’t appear as powerful a lobby as people with HIV • New studies no longer have such strict exclusions • Re-‐use of needles in medical seangs s*ll a problem globally • Will study results be replicable in the ‘real world’? • Will the op*mism turn to pessimism if we fail to deliver? • Experts suggest it may be 25 years to eradicate HCV Happy 50th UKCAB
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