Biotech Values

[DewDiligence]

Sanofi’s Shrinking Stable of Anticoagulant Aspirants

A post on this board about two years ago (#msg-22938795) contains a description of SNY’s anticoagulant pipeline as reported by SNY at an investor presentation in the fall of 2007. The four drug candidates mentioned in the 2007 presentation—and the current status of each—are as follows:


1. AVE5026, a daily injected low-molecular-weight heparin that SNY once described as “the successor to Lovenox.”

Status: SNY once had grandiose plans for AVE5026. However, in late 2008, SNY’s new CEO, Chris Viehbacher, downsized the AVE5026 program to include only VTE prevention following orthopedic surgery or chemotherapy usage. As part of this downsizing decision, the most ambitious phase-3 trial—a comparison of AVE5026 vs Lovenox in 12,000 acutely ill patients with restricted mobility—was terminated prematurely (http://clinicaltrials.gov/ct2/show/NCT00714597 ). Several phase-3 trials of AVE5026 vs Lovenox in VTE prevention that were started in 2007-2008 are still in progress; a few others were recently completed, but SNY has not yet reported their results.


2. Idraparinux, a synthesized, Arixtra-like, injected FXa inhibitor given weekly, which came in two flavors: regular and biotinylated. The biotinylated version (a/k/a SSR126517, idrabiotaparinux) supposedly has the advantage of being reversible with a specific antidote. (Unfractionated heparin and MNTA’s M118 are reversible, but Lovenox, Arixtra, and the new oral anticoagulants are not.)

Status: the regular (non-biotinylated) version of idraparinux caused statsig excess bleeding relative to warfarin in the phase-3 AMADEUS trial in atrial fibrillation; this trial was halted for safety reasons in Feb 2008 (#msg-26298260). As a result, the idraparinux program is likely dead; the new CEO, Chris Viehbacher, said a few months ago, “I would be skeptical of the product.” However, for now the program remains on life support: a phase-3 trial of the biotinylated version vs warfarin in AF that was already underway when the AMADEUS trial was halted is expected to have results in Mar 2011 (http://clinicaltrials.gov/ct2/show/NCT00580216 ).


3. SR123781 (a/k/a/ hexadecasaccharide), a synthesized, Arixtra-like, injected FXa inhibitor with rapid onset and clearance, intended for acute-care settings.

Status: The SR123781 program was terminated in Feb 2008 (http://en.sanofi-aventis.com/binaries/080212_PDF_Slides_media_tcm28-15767.pdf [page 86]). No explanation was given by SNY for the termination, but it’s reasonable to infer that the demise of idraparinux in the AMADEUS trial and the failure of Arixtra to gain significant traction in the commercial marketplace were key factors.


4. Otamixaban, an oral FXa inhibitor.

Status: Otamixaban just finished a phase-2 trial in ACS that I would characterize as a day late and a dollar short: #msg-41012818. I’ll be surprised if SNY advances the program into phase-3.

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All told, the set of four anticoagulant projects described in this post consists of one project that’s defunct, one that’s on life support, one that’s been greatly downsized, and one that’s a day late and a dollar short. Not a pretty picture.