Sanofi Hoping to Move on from Setbacks Like Eplivanserin

September 17, 2009 Sanofi hoping to move on from setbacks like eplivanserin

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It could have been the first major new product for the insomnia market since Sepracor launched Lunesta in 2005 and an important new drug to emerge from Sanofi-Aventis’ ailing pipeline, with the potential to become the French group’s fourth most valuable growth driver over the next six years.

However, the FDA’s complete response letter yesterday for Ciltyri (eplivanserin) requesting further data to establish an adequate benefit-risk profile for the drug looks to have damaged these plans, for now. With little information regarding the extent of the additional information required by the regulator, it would be premature to write off the product just yet, although this is exactly the kind of regulatory setback, for a drug with an already long and chequered developmental history, that new chief executive Chris Viehbacher will be aiming to eradicate through the group’s ongoing R&D restructuring initiatives.

Major new insomnia agent

With analysts previously expecting Ciltyri to be launched late this year and achieving sales of $313m by 2014 the product is, somewhat surprisingly given the relatively modest sales estimates, an important growth driver for the company, especially so given the size of its looming patent cliff when Plavix loses protection in the US in 2011.

Not only is it important to Sanofi, Ciltyri could also be a significant new treatment option for insomnia patients, in a market that is subject to fierce generic competition since Sanofi’s own Ambien lost exclusivity in 2007.

The overall insomnia market has been in steady decline for the past two years and given the high promotional costs and generic competition, some companies have struggled to make any money in this sector; Sepracor’s recent sale to Dainippon Sumitomo Pharma is indicative of this as they continually failed to make any decent return on their significant investment in Lunesta.

Despite the modest sales forecasts for Ciltyri the product is predicted to be the second-biggest selling insomnia drug by 2014, behind Ambien which despite generic erosion continues to dominate the market. WW annual WW insomnia market and top five products sales ($m)

CAGR Generic Pharmacological Patent Rank Product Company Phase 2008 2014 (08 - Name Class Expiry 14)

Sanofi- Ambien IR / Aventis + Apr 1 zolpidem Imidazopyridine Marketed 1,475 697 (12%) CR / Myslee Astellas 2007 Pharma

5-HT2A Sanofi- 2 Ciltyri eplivanserin (serotonin) Filed - - 313 n/a Aventis antagonist

Almorexant Orexin receptor 3 (ACT- almorexant Actelion Phase III - - 223 n/a antagonist 078573)

Sepracor Feb 4 Lunesta eszopiclone GABA agonist Marketed 600 250 (14%) + Eisai 2014

Boehringer 5 Lendormin brotizolam Benzodiazepine Marketed - 121 116 (1%) Ingelheim

Other products 220 269

Total WW insomnia market 2,416 1,867 (4%)

Sanofi has been working on eplivanserin for many years now and has studied the drug in nearly 3,000 patients so far. A serotonin type 2A antagonist, the product was originally developed for obstructive sleep apnoea and schizophrenia but negative trial data in these indications caused the group to abandon further development in 2001.

Attention was then switched to developing the drug for treating chronic insomnia as well as fibromyalgia, with positive phase III data for insomnia reported last year from a number of trials.

However, given the new regime’s stricter approach to R&D at Sanofi (Sanofi's pipeline cull points to more ruthless approach, April 29, 2009) it is doubtful whether the drug would ever have reached this far. It will be interesting to see whether, if the FDA does require further trials, the new management will consider this project worthy of any more investment.