Sanofi-Aventis Pipeline Includes Sleep Quality Aid, Depression Therapy

Positive early clinical results for Sanofi-Aventis' sleep disorder therapy eplivanserin could lead to the development of a "new concept" for improving quality of sleep, Senior Exec VP-Science & Medical Affairs Gerard Le Fur said.

Sanofi-Aventis discussed the status of the firm's Phase IIb/III pipeline during an earnings presentation Aug. 31.

In a recent Phase IIb clinical trial of eplivanserin, the 5HT2A receptor antagonist met the study's primary endpoint to improve sleep maintenance.

The multicenter, double-blind, placebo-controlled trial of 350 patients with sleep maintenance insomnia demonstrated that eplivanserin reduced wake after sleep onset and the number of awakenings compared to placebo.

The drug also increased total sleep time and improved refreshing quality of sleep with no next-day residual effect or rebound insomnia observed after treatment discontinuation, the company reported.

Eplivanserin could be a novel approach to sleep assistance, Le Fur stated. Unlike currently marketed therapies, including Sanofi-Aventis' own Ambien (zolpidem), the drug does not induce sleep, but rather improves quality of sleep. The therapy will move into Phase III trials next year, he said.

Sanofi-Aventis currently is pursuing eplivanserin as a monotherapy, but may consider studying the drug in combination with Ambien, Exec VP-Pharmaceutical Operations Hanspeter Spek noted.

The drug maker is still aiming to launch a controlled-release version of zolpidem, Ambien CR , by the end of the summer, Le Fur said. Sanofi-Aventis has been in discussions with FDA over labeling of the insomnia agent for treatment duration since April.

Spek hinted at an imminent approval for Ambien CR, stating that he would feel more comfortable discussing commercialization strategies for the drug "next week."

If approval is granted within the next few weeks, the firm would have about a year to establish the new formulation before Ambien's exclusivity expiration in October 2006 (¹ (Also see "Sanofi Ambien Line Extension Planned For 2004; Still Confident In Arixtra   " - Pink Sheet, 24 Feb, 2003.), p. 15).

Sanofi-Aventis' R&D portfolio includes 128 products under development: 51 in Phase II and III and 77 in preclinical or Phase I studies.

The company reported mixed results from clinical trials on SR 58611, a beta-3 antagonist, for the treatment of recurrent major depression.

A Phase III study of 280 patients in Europe met its primary objective of demonstrating an improvement in depressive symptoms over placebo after six weeks of treatment, the company reported.

However, a similar Phase III trial in North America was inconclusive, showing no significant efficacy difference compared to placebo.

In addition, early-stage studies are being conducted for the oncology therapy alvocidib, a synthetic derivative of the flavonoid rohitukine, for the treatment of refractory chronic lymphocytic leukemia. Research on the therapy had been discontinued by Aventis.

The drug exhibited an "abnormally high" response in fourth-line CLL patients, according to Le Fur. In a study of 23 patients with CLL who failed fludarabine treatment, alvocidib activity was shown to be comparable to that of second-line alemtuzumab (Genzyme/Schering AG's Campath ) or fludarabine with an acceptable safety profile.

Other ongoing Phase IIb/III projects include SSR 591813 for smoking cessation. In a Phase IIb study of 527 patients, the nicotine agonist met its primary objective of prolonged abstinence during the last four weeks of therapy.

Xaliproden for treatment of severe peripheral sensory neuropathy induced by chemotherapy also is in trials. A Phase III study in 649 patients with metastatic colorectal cancer treated with the FOLFOX-4 regimen showed xaliproden decreased the occurrence of severe PSN without negatively impacting the response rate of chemotherapy, the firm reported. Xaliproden also is in Phase III for treatment of Alzheimer's disease.

Two research programs in Phase IIb/III have been halted: the evaluation of the ICE inhibitor pranalcasan for treatment of rheumatoid and osteoarthritis, and the NK-3 receptor agonist osanetant for schizophrenia.