Vertex’s hep C plans play second fiddle to cystic fibrosis

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The game of musical chairs going on in Vertex Pharmaceuticals’ early-stage hepatitis C pipeline has scored an overall positive result, with the company’s nucleoside polymerase inhibitor ALS-2200 chosen to progress into phase II development.

However, it all seems like an increasingly irrelevant sideshow given Gilead Sciences’ march towards launching the first all-oral interferon-free regimen. Indeed, while Vertex was once the antiviral specialist, analysts now view it largely as a cystic fibrosis company, and EvaluatePharma data reveal that by 2018 they are expecting the respiratory area to account for 94% of group revenue.

Vertex reported positive findings from a phase I study of ALS-2200, and confirmed that later this year it would begin phase II trials of it in combination with ribavirin and with its marketed protease inhibitor Incivek. The results, from a combination with ribavirin, showed good tolerability and a median 4.18 log10 decline from baseline viral load after seven days, with two out of eight patients achieving undetectable HCV RNA levels.

This was a smaller effect than the -4.54 seen in the monotherapy cohort, although the baseline viral load was lower in the combination arm; in any case the small size of the cohort makes direct comparisons impossible. Vertex’s other nucleoside polymerase inhibitor, ALS-2158, has been dropped in phase I after showing insufficient antiviral activity, although Vertex declined to give its effect on antiviral load.

ISI Group’s Mark Schoenebaum said the efficacy of ALS-2200 seemed sufficiently strong to justify moving it forward.

Lagging Gilead

Nevertheless, although ahead of ALS-2200 Vertex also has a phase II non-nucleoside polymerase inhibitor, VX-222, it is lagging Gilead in developing an oral, interferon-free regimen. Gilead’s GS-7977, a nucleoside polymerase inhibitor, is in phase III and could become the first to hit this hepatitis C holy grail.

In fact, Gilead has been given an almost clear run at the space following setbacks with other nucleoside polymerase inhibitors, such as Idenix Pharmaceuticals’ IDX184, which has been suspended and handed back by Novartis, and Bristol-Myers Squibb’s BMS-986094, acquired through the $2.5bn purchase of Inhibitex but recently scrapped (Gilead benefits from Bristol-Myers’ stumble in hep C chase, August 2, 2012).

And sales of Incivek and the other recently launched protease inhibitor, Merck & Co’s Victrelis, have disappointed and are expected to fall sharply after the expected 2014 launch of GS-7977; both Incivek and Victrelis are given on top of interferon.

A respiratory play?

As such, in a recent note UBS analysts said Vertex was now “more of a cystic fibrosis play”. The company’s other recently launched drug, Kalydeco, is marketed for this indication and EvaluatePharma estimates that it has an NPV of $4.9bn.

Although Kalydeco still has much to prove, and a phase II data foul-up of its combination with the follow-on agent VX-809 dented confidence, the cystic fibrosis franchise combined should account for almost $2bn of revenue by 2018, according to consensus forecasts (Vertex will struggle to restore confidence until more data emerge, June 29, 2012).

Sentiment could be lifted when the company presents full data from the phase II Kalydeco/VX-809 combination study at the North American Cystic Fibrosis Conference on October 10-13. Meanwhile, additional data on ALS-2200 could be presented at the AASLD meeting in November, although the more important results will concern 12-week safety, and are unlikely before next year’s Easl conference.

Vertex had licensed both ALS-2200 and ALS-2158 from the private company Alios BioPharma a year ago for $60m up front. While the latter is based on adenosine, ALS-2200 is a uridine-based analogue – as is Gilead’s GS-7977. Such considerations might be important if, as some believe, the setbacks with the Idenix and Bristol-Myers Squibb nucleoside polymerase inhibitors – both are guanosine analogues – relate to their active metabolites.

To be sure, Vertex still has a good shot at a significant indication, and an estimated large pool of “warehoused” hepatitis C patients awaiting launch of a non-interferon regimen should expand the market. But its antiviral franchise seems to have been overtaken by events.

Vertex's phase I nucleoside NS5B polymerase inhibitors
Project Nucleoside analogue structure Trial ID Notes
ALS-2200 Uridine-based NCT01590407 Two phase II studies planned
ALS-2158 Adenosine-based NCT01554085 Dicsontinued for lack of efficacy

To contact the writer of this story email Jacob Plieth in London at jacobp@epvantage.com

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