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Another Hep C Safety Worry Buffets Achillion's Lead

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Another Hep C Safety Worry Buffets Achillion's Lead July 02, 2013 Another hep C safety worry buffets Achillion’s lead Jonathan Gardner The fact that big pharma has overlooked sovaprevir in the red-hot hepatitis C market probably should have prompted concern on the part of Achillion Pharmaceuticals investors over its chances of winning a significant share of the market. The FDA’s clinical hold announced yesterday, based on signs of liver toxicity in a drug interaction study, was yet another setback for the Connecticut-based group. Shares fell 23% to $6.40 in early trading today following the post-market disclosure of the hold, which curiously has not affected a phase II trial of the protease inhibitor in combination with Achillion's NS5A inhibitor ACH-3102. The company’s chief executive, Milind Deshpande, said the hold will not affect its timeline of launching phase III trials at the end of 2014; however, the news is a clear knock to sentiment as Gilead Sciences looks increasingly likely to absorb a huge chunk of patients. Data needed The phase I trial in healthy subjects detected elevations in alanine transaminase (ALT) in five of 31 healthy subjects taking part in a drug interaction study of sovaprevir with ritonavir-boosted Reyataz. The Bristol-Myers Squibb drug is the most widely prescribed protease inhibitor for HIV, and as such Achillion needed to demonstrate that it can be taken simultaneously with sovaprevir in order to be used in patients co-infected with hep C. Mr Milind Deshpande said no ALT elevations had been seen in early phases of the trial, which saw each drug dosed independently of the other. Pharmacokinetic studies indicate a metabolic interaction that caused increases in plasma concentrations of both compounds during the co-administration phase of the study; the ALT increases did not meet the criteria of a serious adverse event. The FDA has asked for data from all drug interaction study and a safety analysis from ongoing trials, information that the company said will take six weeks to provide. The trial of sovaprevir with ACH-3102 was allowed to continue recruitment and dosing, in part because it is being conducted under the investigational new drug programme for ‘3102. Keeping that trial open was a specific FDA recommendation, according to chief medical officer David Apelian. “That study is very clean,” Dr Apelian told analysts in a conference call. Those assurances clearly did not soothe investors. Given that promising drugs like Bristol-Myers Squibb’s BMS- 986094 – now remembered as a $2.5bn mistake – Idenix’s IDX184, and BioCryst Pharmaceuticals' BCX5191 have all suffered from toxicity worries in the past year, learning that investigators had detected a signal in sovaprevir could not lend any confidence. Sovaprevir is forecast to earn the company $256m in royalties in 2018, according to EvaluatePharma’s consensus. Shaken confidence It is not as though the group has been riding the biotech bubble. Although Achillion rose to a five year high of $12.37, valuing the company at nearly $1bn, following Gilead Sciences’ $11bn buyout of Pharmasset, its fortunes have ebbed in the 19 months since. The investment case is built around its eventual acquisition, and that depends in part on its ability to show some differentiation from Gilead’s sofsobuvir-lepidsasvir combination in phase III. It is not entirely clear how big the market is in the US or elsewhere, but there is reason to believe that the first company to hit the market with an all-oral combination free of interferon and ribavirin will grab a huge share of patients in the wealthy Western markets – even more so if, as Gilead is planning, that combination is a single pill. Given the size and diversity of the hep C population, there still may be much to play for amongst Gilead’s competitors. One of the selling points of its pipeline has been the pan-genotypic effects of ‘3102, although with sofosbuvir and a standard backbone therapy having been filed in multiple genotypes, that hope of differentiation may be dissipating. Others have been focusing on special populations, such as those with treatment resistant infections, liver transplants, cirrhosis or co-infections (AASLD – Hep C competitors cede space to Gilead and Bristol-Myers and turn to niche uses, November 12, 2012). With a clear drug interaction, questions have to be raised about sovaprevir’s use in the HIV co-infected population. Still, the compound cannot be completely written off, even if it looks like the finish line is looking further away. Leerink Swann analyst Howard Liang wrote today that the issue is “resolvable” given that it is limited to the combination with Reyataz, and even if not ‘3102 is the more value asset. As one of the last independent, pure-play hep C companies left in the market, Achillion is being closely watched even if the spotlight seems to be largely on Gilead and its big pharma competitors Bristol-Myers and AbbVie. To stumble so publicly does not build confidence in its pipeline. To contact the writer of this story email Jonathan Gardner in London at [email protected] or follow @JonEPVantage on Twitter More from Evaluate Vantage Evaluate HQ 44-(0)20-7377-0800 Evaluate Americas +1-617-573-9450 Evaluate APAC +81-(0)80-1164-4754 © Copyright 2021 Evaluate Ltd..
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