Sanofi Aventis' discontinuation of 14 pipeline projects is only the first part of a larger R&D transformation initiative. Now that the firm has completed a pipeline review, it will determine a set of key technologies and disease areas and come up with a new R&D organization.

The firm announced the move to terminate 14 projects, including seven mid- to late-stage compounds, during its first quarter sales and earnings call April 29. The cuts are the outcome of a lengthy pipeline review, conducted by an in-house team and external consultants who examined scientific, medical, commercial, regulatory and market access criteria. The end result was that four Phase III, four Phase II, and six Phase I projects were discontinued.

"We made some decisions [with our Phase II and Phase III programs] on the basis of either the product didn't have sufficient efficacy, there were safety issues, or they really didn't deliver what we were looking for in terms of added-value to patients," Sanofi CEO Chris Viehbacher said in a Q&A published April 29 in conjunction with the earnings release.

Announcement of the R&D transformation - more details of which will be given during the second-quarter earnings release - is consistent with the Sanofi board's stated charge to Viehbacher, when the former GlaxoSmithKline North American president took the helm last year as CEO of Sanofi (¹ Also see "GSK’s Viehbacher Charged To “Adapt” Sanofi-Aventis To New Realities" - Pink Sheet, 15 September, 2008., p. 13).

Last summer the firm announced it was ending some once-promising advanced development projects in light of clinical setbacks and a broader overhaul, and signaled that the fate of others hinged on the strategic pipeline review (² Also see "Sanofi-Aventis Pares Pipeline, Ditches Antidepressant Amibegron" - Pink Sheet, 11 August, 2008., p. 7).

One of the compounds that was in doubt back then has in fact met its demise. The Phase III antidepressant saredutant has been cut, after results from a study in association with escitalopram were reviewed. The NK2 antagonist had missed the mark in placebo-controlled studies, though with good long-term tolerability, so Sanofi was waiting on the results of combination trials with paroxetine and escitalopram.

Another of the halted Phase III programs was for the hypercholesterolemia therapy AVE5530 - because of insufficient efficacy. Sanofi has also discontinued the Unifive pentavalent vaccine project (STC-HepB-Hib) to reallocate resources to the hexavalent vaccine Hexaxim (STP-HepB-Polio-Hib). The final Phase III loss was the therapeutic renal and colorectal cancer vaccine TroVax ; Sanofi returned the rights to Oxford BioMedica, and instead is starting up a new collaboration in ophthalmology ( ³ Also see "Sanofi Trades In Phase III TroVax For Early-Stage Ophthalmology Deal" - Pink Sheet, 29 April, 2009. ).

The discontinued Phase II programs include AVE657 for sleep apnea, SSR180575 for diabetic polyneuropathy, the anti-IGF 1 oncologic AVE1642 (with rights returned to ImmunoGen), and the firm's melanoma vaccine.

Projects in purgatory

Four other projects are also potentially on the chopping block, with go/no-go decisions to come in the next few months as clinical trial results roll in.

The most notable of the projects still in review is the follow-on to the blockbuster antiplatelet Plavix (clopidogrel): idrabiotaparinux, for deep vein thrombosis/pulmonary embolism and atrial fibrillation. As with all blood-thinners, the potential for bleeding events exists. Viehbacher said that though no signal has yet surfaced, the firm's decision to continue development will be contingent on FDA's comfort with the drug's safety profile. The agency's decisions on the pending prasugrel (Lilly/Daiichi Sankyo's Effient ) and rivaroxaban (J&J's Xarelto ) might soon give some clarity on that front.

"On idrabiotaparinux, I think it's useful to give you a little bit of a sense of what goes on behind the curtains. I would be skeptical of the product," Viehbacher said. On the other hand, the CEO noted, "[Senior VP-R&D] Marc [Cluzel] is passionate about the product. I think that's a healthy thing. There are plenty of people that would tell you that Plavix would never have seen the light of day if R&D hadn't been passionate about it."

Other projects hanging in the balance include AVE1625 for schizophrenia, xaliprodene for peripheral sensory neuropathies, and a West Nile virus vaccine.

"I think that what is important is that you don't kill that passion on the scientific side, but you do put in place a number of milestones," Viehbacher said.

"It's not all so black and white here, and I personally have a huge respect for our R&D colleagues who really do believe in a product, because at the end of the day, when we look at the history of the industry, sometimes that belief has really triumphed over commercial logic. ...We know these are some projects where not everybody would see immediate benefit, but we have identified milestones, we have a process and I think an objective way of looking at this."

Sanofi's streamlined pipeline now consists of 51 projects, 21 of which are in Phase III or pending at FDA.

-Jamie Hammon (j.hammon@elsevier.com)

Sanofi Cuts Development Of 14 Drugs In First Quarter, With More R&D Changes To Come

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