Given the fast-paced progress in treating hepatitis C, international medical meetings dealing with liver disease are some of the most eagerly awaited and EASL’s International Liver Congress later this month looks like it will deliver some of the most important data of the year. Trial results from closely watched molecules developed by Abbott and Gilead amongst the bigger names, along with Medivir and Idenix amongst the smaller, should help define future treatment protocols in treating the viral disease.
Shares in Abbott climbed 1% to $61.46 and Idenix fell 12% to $9 yesterday following release of abstract data as investors passed judgement on the findings. Data from all of the drugs competing for a share of the market, estimated at $5.8bn in 2016, suggest that researchers are getting tantalisingly close to the holy grail of all-oral interferon free therapies (see table).
Abbott already appears to have established itself as an early winner from EASL. Shares are at a record high, not the least because of the positive reception from the company’s plans to spin off its pharma division (Demand for big pharma shares continues in Q1; Regeneron stand out gainer in mid-caps, April 4, 2012).
The findings of the Co-Pilot trial suggest that its all-oral cocktail of protease inhibitor ABT-450 and non-nucleoside NS5B polymerase inhibitor ABT-333 combined with a backbone of antivirals, Abbott’s Norvir and hep C standard ribavirin, may succeed as an interferon-free regimen. Interferon, and its flu-like side effects, is considered a barrier to treatment for many.
Results from the phase II trial showed the combination achieved more than a 90% sustained viral response at 12 weeks in previously untreated patients with genotype 1, the hardest to treat and most common strain in the US, and nearly 50% in previously treated patients.
A second phase II trial, Pilot, found the backbone of ABT-450, Norvir and ribavirin combined with Abbot’s second oral polymerase inhibitor ABT-072 generated a sustained viral response of greater than 90% after 12 weeks among previously untreated genotype 1 patients with the CC allele of the IL28b gene, considered the easiest-to-treat of the three alleles of that gene.
It is still of course several years from the market even if the phase II results are confirmed, but the results have raised hope that an interferon-free treatment could be on the market sooner than experts believed even a year ago (EASL - Beyond protease inhibitors hep C pipeline filling up, April 4, 2011).
|Selected EASL presentations for hepatitis C candidates|
|Company||Product||Pharma class||Study||Clinical trial ID|
|Abbott Laboratories||ABT-450 + ABT-072||Hepatitis C protease inhibitor + Hepatitis C non-nucleoside NS5B polymerase inhibitor||Pilot||NCT01221298|
|ABT-450 + ABT-333||Hepatitis C protease inhibitor + Hepatitis C non-nucleoside NS5B polymerase inhibitor||Co-pilot||NCT01306617|
|Achillion Pharmaceuticals||ACH-1625||Hepatitis C NS3 protease inhibitor||-||NCT01180790|
|ACH-3102||Hepatitis C NS5A inhibitor||-||Preclinical|
|Boehringer Ingelheim||BI 201335 + BI 207127||Hepatitis C NS3/4A protease inhibitor + Hepatitis C non-nucleoside NS5B polymerase inhibitor||Sound-C2||NCT01132313|
|Bristol-Myers Squibb||BMS-790052 + BMS 650032||Hepatitis C NS5A inhibitor + Hepatitis C NS3 protease inhibitor||G1b null Japanese||NCT01051414|
|Gilead Sciences||PSI-7977||Hepatitis C nucleoside NS5B polymerase inhibitor||Atomic||NCT01329978|
|GS 9256 + GS 9190||Hepatitis C NS3 inhibitor + Hepatitis C non-nucleoside NS5B polymerase inhibitor||-||NCT01225380|
|Medivir/Johnson&Johnson||TMC435||Hepatitis C protease inhibitor||Aspire||NCT00980330|
|Merck & Co||Victrelis||Hepatitis C protease inhibitor||Provide||NCT00910624|
|Roche||RG7128||Hepatitis C nucleoside NS5B polymerase inhibitor||Jump-C||NCT01057667|
|Vertex Pharmaceuticals||VX-222||Hepatitis C non-nucleoside NS5B polymerase inhibitor||Zenith||NCT01080222|
Gilead Sciences and Bristol-Myers Squibb will be hoping trial findings validate some recent strategic decisions. Gilead’s surprising $11bn buyout of Pharmasset was the second-biggest biotech takeout of 2011 and was done primarily to secure PSI-7977, a drug that at the time had reported only phase II data.
Late-breaking data from the Proton, Electron and Atomic trials of ‘7977 are still under embargo; the most important of them might be the all-oral Electron trial, which is in the easier to treat genotype 2 and 3 populations. The release of topline results from that trial caused a hiccup when the California group revealed earlier this year that a majority of treatment resistant patients relapsed following 12 weeks of treatment (Expectations reined in as Gilead hits bump on the hep C road, February 17, 2012).
The Proton and Atomic trials rely on a background of interferon and ribavirin, so they may not have quite the star quality of those all-oral combinations; however, Atomic is a test across four genotypes and as such may demonstrate the agent’s versatility.
It is a bit of a surprise that Bristol-Myers Squibb does not appear to be releasing experimental data from its catch of the year, INX-189, brought on board with $2.5bn buyout of Inhibitex. BMS is detailing data on its dual oral therapy of BMS-790052 and BMS-650032 (daclatasvir/asunaprevir) in patients resistant to therapy or unable to take interferon. Data will be released from a Japanese trial showing sustained viral response at 12 weeks was achieved in 90% of treatment failures and 64% of patients unable to take interferon.
Late-breaking data is also expected from Debiopharm’s Novartis-partnered alisporivir, a cyclophilin inhibitor and Medivir’s Johnson & Johnson partnered TMC435.
Given the pace of progress, an all-oral hepatitis C treatment seems to be approaching more quickly than many anticipated. Not all of the next generation of agents will succeed, but given the amount of research being detailed this month optimism is clearly rising.