Pessimism Infects Achillion As FDA Sustains Clinical Hold

September 30, 2013 Pessimism infects Achillion as FDA sustains clinical hold

Jonathan Gardner

Another disappointment for the hepatitis C project sovaprevir may have Achillion Pharmaceuticals feeling like it is starting all over again. At a time when the Connecticut-based group could be riding the bio-runup heading into the AASLD liver meeting in November, executives disclosed that the FDA would not lift the clinical hold imposed after liver enzyme elevations were detected in a drug interaction study (Another hep C safety worry buffets Achillion’s lead, July 2, 2013).

Shares crashed 55% to a four-year low of $3.28 in early trading today on the news, released after Friday’s market close. Acknowledging the setback, executives signalled that they were prepared to move on, with phase II testing of alternative treatment regimens imminent; while that may be an attempt to reassure, it adds months if not years to investors’ assumptions about when Achillion will start generating a royalty stream.

Just like starting over

With first approval decisions for Gilead Sciences’ expected $11bn drug sofosbuvir due by December and combinations from Bristol-Myers Squibb and AbbVie making strides forward, the all-oral market looks to be well served by 2017. This year is the likely earliest point that any of Achillion’s assets could begin generating sales; in 2017, Gilead’s sofosbuvir-centred franchise is expected to yield $8.2bn in sales, according to EvaluatePharma's consensus.

However, Achillion executives sought to portray the company's hep C activities as broader than sovaprevir, a protease inhibitor, highlighting the NS5A inhibitor ACH-3102, a second protease inhibitor, ACH-2684, which will report combination tests with ‘3102 next year, and a uridine-analog nucleotide, ACH-3422, which could be in the clinic next year.

Perhaps more damning for sovaprevir were early data from phase II combination trials with ‘3102 and ribavirin: two cases of viral rebound and two other patients in whom the virus was not sufficiently suppressed meant the combination achieved a rapid viral response rate at four weeks of 78% in genotype 1 patients. With Achillion shooting for a sustained viral response (SVR) of 90% after end of the treatment regimen, the combination might not be robust enough to meet the company’s own strategic aims – chief executive Milind Deshpande acknowledged that it looked like the combination would only reach 80% SVR.

Nevertheless, Mr Deshpande insisted that it would be “premature and irresponsible” to walk away from sovaprevir and pledged to provide regulators with the additional data to ease worries about alanine transaminase elevations detected in the phase I drug-interaction study with Norvir-boosted Reyataz. He added, “At the same time, ‘2684 is a great asset. It was for multiple reasons we did not advance ‘2684, which had nothing to do with the clinical characteristics. We had always viewed ‘2684 as a great backup compound.”

Plan B

With moves afoot to execute a plan B, the investor reaction is not surprising. The trouble is that, as far as Achillion is behind the big pharma leaders, whether a significant market will exist, and where it will be, have to be leading questions.

It is true that 2-3% of the world’s population, or 150-170 million people, are estimated to be infected with the virus, and in many developed nations millions are believed to be awaiting a treatment regimen without the side effect profile of the well-established interferon and ribavirin – the introduction of Vertex Pharmaceuticals’ Incivek and Merck & Co’s Victrelis in 2011 has not eliminated those drugs.

Canny drug developers have been looking for niche populations outside the genotype 1 being treated by Incivek and Victrelis – other genotypes, relapsed patients, HIV co-infected patients and those with cirrhosis or who have undergone liver transplants are all challenging groups that can be targeted. Even so, the big developers are already there in many cases (AASLD – Hep C competitors cede space to Gilead and Bristol- Myers and turn to niche uses, November 12, 2012).

Achillion, for one, has emphasised the pan-genotypic nature of its R&D portfolio. The first approvals of Gilead’s sofosbuvir as a monotherapy will likely cover genotypes 1 through 6 – assisted with ribavirin in genotypes 2 and 3 and interferon-ribavirin in the remaining four, giving any combination that can eliminate one or both a competitive advantage.

However, based on the early data from the sofosbuvir/ACH-3102 trial, it is not at all certain that Achillion’s assets can compete without an additional antiviral boost. Unless Achillion gets some spectacular results soon it risks being simply left too far behind to compete.

Trial ID

Sovaprevir/ACH-3102 in combination with ribavirin in treatment naïve patients NCT01849562

To contact the writer of this story email Jonathan Gardner in London at [email protected] or follow @JonEPVantage on Twitter