Astellas To Explore IBS Endpoints Before Advancing Ramosetron Into Phase III

Japanese pharma hopes its novel 5-HT3 antagonist will enter Phase III trials in 2008 after completion of an FDA-requested study of endpoints used in irritable bowel syndrome trials.

Astellas Pharmaceuticals could enter U.S. Phase III studies with its diarrhea-predominant irritable bowel syndrome agent YM060 (ramosetron) as soon as the first half of 2008, Executive VP Toshinari Tamura told analysts during a third quarter earnings call Feb. 1.

However, before the trial can gain approval, FDA has asked the Tokyo-based company to conduct an exploratory study to identify "special" endpoints for IBS, Tamura said. "They are asking us to review the disease itself and consider what would be the most appropriate endpoints and to validate those endpoints."

In completed Phase II studies in Europe, YM060, a 5-HT3 receptor antagonist, showed "good efficacy using the endpoints we set," he said. Tamara said FDA has no problems with safety or with the data obtained with the European study endpoints. "They are satisfied with that - they are asking for additional endpoints."

Novartis' Zelnorm (tegaserod), a 5-HT4-receptor inhibitor is approved for treatment of IBS with constipation. During a recent earnings call, Novartis Pharmaceuticals CEO Thomas Ebeling touted the blockbuster potential of the IBS therapy, which had sales of $561 million in 2006 (¹ (Also see "Novartis Bullish About Prexige; Anticipates Blockbuster Potential" - Pink Sheet, 18 Jan, 2007.)).

Tamara also told analysts that FDA has granted fast-track designation for the oncologic YM155, a survivin suppressant, in diffuse large B-cell lymphoma. Enrollment has completed in Phase II monotherapy trials in hormone-refractory prostate cancer, non-small cell lung cancer and metastatic melanoma. A Phase II trial in non-Hodgkin's lymphoma is also planned, he said.

Also in the U.S. pipeline, ASP2151, an inhibitor of helicase-primase complex, is in Phase II trials for genital herpes and herpes zoster. Tamura noted that the drug is the first new molecular entity to enter Phase II bearing the designation "ASP," for Astellas Pharmaceuticals.

Astellas was formed in 2005 from the merger of two Japanese pharmaceutical companies: Yamanouchi and Fujisawa. Japanese Pharmaceutical consolidations and collaborations are affecting the dynamic of global biotech licensing deals, attendees heard last week at BIO-Asia (² (Also see "Japanese Mergers Provide Opening For Biotech Deals – Novartis Licensing Head" - Pink Sheet, 31 Jan, 2007.)).

During the call, Tamura noted a recent agreement with another Tokyo-based company, Kirin Brewery, to develop a fully human anti-CD40 antagonistic monoclonal antibody for prophylaxis of organ rejection.

The status of an NDA for Prograf MR (FK506MR), a modified-release formulation of Astellas' Prograf (tacrolimus) for prophylaxis of organ rejection in transplantation is still up in the air, Tamara said. Last week FDA deemed the product "approvable" for kidney and liver transplant patients and "not approvable" in heart transplantation (³ (Also see "Astellas’ Once-Daily Prograf Receives Mixed Decisions For Three Prophylaxis Claims" - Pink Sheet, 24 Jan, 2007.)).

Astellas reported global net sales of ¥702.5 billion ($5.79 billion) for the first three quarters of fiscal 2006, a year over year increase of ¥23.7 billion ($195 million).

North American prescription sales for the period were ¥128.5 billion ($1.1 billion) compared with ¥107.5 billion ($885 million) in the first three months of fiscal 2005. Tamura credited the increase to a "strong upward trend" in Prograf, which contributed ¥21.7 ($178.7 million).

Vesicare (solifenacin) is on track to hit a full-year North American sales target of ¥16.5 billion ($135.9 million), Tamura said. For the first three months of fiscal 2006, sales totaled ¥12 billion ($98.8 million). Astellas and development partner GlaxoSmithKline launched the overactive bladder treatment in 2005.

-Shirley Haley ([email protected])