Pfizer will resubmit the NDA for its next-generation selective estrogen receptor modulator lasofoxifene in December with new data, the drug maker said in a pipeline update released Aug. 6.

The company received a "not approvable" letter in September 2005 on its NDA for lasofoxifene (¹ Also see "Pfizer’s Oporia Is “Not Approvable” For Osteoporosis Prevention" - Pink Sheet, 13 September, 2005.).

At the time, Pfizer and partner Ligand were poised to compete with Lilly's SERM Evista (raloxifene) as a preventative for postmenopausal osteoporosis, touting their drug's "improved profile" in clinical measurements of bone preservation (² Also see "Pfizer/Ligand's Lasofoxifene Is First "Next-Generation" SERM Filed At FDA" - Pink Sheet, 17 September, 2004.).

Now, there may be other competition in the offing. Wyeth submitted a complete response at the end of June for an "approvable" letter it received for its SERM Viviant (bazedoxifene) and anticipates that FDA will extend its review of the osteoporosis prevention claim to the end of the year.

Pfizer has 85 new molecular entities in development along with 14 potential new indications or enhancements for in-line products, such as Lyrica (pregabalin), Geodon (ziprasidone) and the newly approved HIV therapy Selzentry (maraviroc), the company said. Of 99 total programs, 38 are in Phase I, 47 are in Phase II and 11 are in Phase III; 27 programs have advanced since the last update in December (³ Also see "Pfizer Plans Four New Products A Year Starting In 2011" - Pink Sheet, 30 November, 2006.). Overall, 13 programs have been discontinued since then.

"Our progress is especially gratifying since we are continuing to make major structural and organizational changes while we pursue all of these opportunities," Pfizer President of Global Research and Development John LaMattina said. "We are revising the allocation of our capital so that we target the areas of greatest medical and commercial promise."

In oncology, where Pfizer said it invests more than 20 percent of its development budget, the firm lists 20 programs. Axitinib, a VEGF/tyrosine kinase inhibitor, has entered Phase III for thyroid cancer, and in July the first patient was dosed in a Phase III pancreatic cancer trial, Pfizer said, adding that "there is new data showing that [axitinib] prolonged overall survival in advanced pancreatic cancer when combined with standard care chemotherapy."

Pfizer's plans for adding to the franchise for its cancer drug Sutent (sunitinib) continue, with Phase III studies in patients with non-small cell lung cancer and breast cancer "progressing well" and the first patient now dosed in a Phase III colorectal cancer study. Sutent generated $219 million in sales in 2006, its first year on the market as a therapy for advanced renal cell carcinoma and gastrointestinal stromal tumors (⁴ Also see "Sutent Labeling Updated To Reflect First-Line Renal Cell Carcinoma Data" - Pink Sheet, 9 February, 2007.).

CP-751871, one of six oncology candidates in Phase II development, works by a novel mechanism of action that "represents a new generation of immunotherapy" and has shown "favorable survival outcomes in patients with metastatic melanoma with limited treatment options," Pfizer said. In addition, data is expected in 2008 from Phase III studies of CP-675206, a CTLA4 receptor antagonist, in melanoma.

In cardiovascular diseases, Phase II trials of the Factor Xa inhibitor apixaban for treatment of thrombosis have been completed, while Phase II studies evaluating the therapy for acute coronary syndromes are ongoing, Pfizer said.

A Phase III trial is underway to study apixaban for prevention of stroke in patients with atrial fibrillation, and a further Phase III trial is planned to compare apixaban to Sanofi-Aventis' Lovenox (enoxaparin) in the prevention of venous thromboembolism in patients undergoing total knee replacement surgery, the company said.

Pfizer and Bristol-Myers Squibb inked a billion-dollar development and commercialization deal for apixaban in April, noting their intention to file a marketing application in the second half of 2009 for the prevention of venous thromboembolism (⁵ Also see "Bristol And Pfizer Team Up To Develop Anticoagulant Apixaban In $1 Billion Deal" - Pink Sheet, 26 April, 2007.).

Meanwhile, in July, Johnson & Johnson and Bayer HealthCare announced that they would file an NDA in 2008 for their jointly developed oral Factor Xa inhibitor Xarelto (rivaroxaban) for venous thromboembolism prevention after major orthopedic surgery, after it demonstrated superior efficacy to Lovenox (⁶ Also see "J&J/Bayer’s Once-Daily Rivaroxaban Superior To Lovenox In Phase III Trial" - Pink Sheet, 9 July, 2007.).

In infectious disease, Pfizer announced yesterday that its first-in-class CCR5 antagonist Selzentry received FDA approval for treatment-experienced patients with HIV (⁷ Also see "Pfizer’s Selzentry Wins FDA Approval For HIV" - Pink Sheet, 6 August, 2007.). Pfizer is also studying maraviroc in Phase II for rheumatoid arthritis.

With a record 47 programs in Phase II development, Pfizer is on target to reach its goal of tripling its Phase III portfolio by 2009 and introducing four new products a year beginning in 2011, CEO Jeff Kindler said. "We will continue to sharpen the focus and simplify the structure of our R&D organization so that we bring our pipeline forward to commercialization as rapidly as possible and enhance our productivity in all aspects of our clinical work."

In January, Pfizer announced a sweeping restructuring plan that includes elimination of 10,000 positions and a series of base closings aimed at enhancing the flexibility of its research and development efforts (⁸ Also see "Pfizer Looks To Make Its Big Pharma Engine More Agile By Cutting 10,000" - Pink Sheet, 22 January, 2007.).

- Shirley Haley (s.haley@elsevier.com)

Pfizer Pipeline Update Includes Resubmission Plans For Osteoporosis Drug Lasofoxifene

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