Pfizer may be facing yet another Phase III failure with the June 24 announcement that it is suspending worldwide clinical development of tanezumab for pain related to osteoarthritis following a request by FDA.

On June 23, the agency called for the halt of a 10-trial, 7,000-plus patient Phase III program because a small number of patients experienced worsening osteoarthritis that led to joint replacement. Pfizer would not confirm the number of those patients, but in a June 24 note, Leerink Swann analyst Seamus Fernandez pegged it in "the low double-digits."

Pfizer continues to test tanezumab, a monoclonal antibody that inhibits nerve growth factor, in a series of Phase II trials in cancer pain, chronic lower back pain, interstitial cystitis, and diabetic neuropathy. FDA and Pfizer were slated to review adverse event data from these studies later this week with the possibility that the agency might recommend halting the entire program.

Pfizer said the need for joint replacement has not been observed in other patient populations taking tanezumab. Fernandez noted that some pain specialists have speculated that masking moderate to severe osteoarthritis pain, which tanezumab is intended to do, could lead to rapid joint deterioration.

Meanwhile, Bernstein Research's Tim Anderson, also in a June 24 note, said that patients receiving tanezumab have reported numbness, dizziness and edema, as well. "The long-term consequences of NGF inhibition will probably be difficult to fully characterize," he wrote.

"Pfizer believes chronic pain is an important condition to treat," a company spokesman said in an interview. "We're going to continue to work with the FDA to assess the potential implications for the ongoing tanezumab clinical trial program."

He added that Pfizer makes patient safety a top priority and will seek the course of action that is most appropriate for patients.

The problems with tanezumab occur a few months after Pfizer got disappointing Phase III data for Alzheimer's disease drug Dimebon (latrepirdine) and the same week the company had to pull oncology drug Mylotarg (gemtuzumab ozogamicin) from the market. These disappointments follow Pfizer's biggest failure in recent memory, the Phase III flameout of cholesterol candidate torcetrapib in 2006 (Also see "Best Laid Plans: Pfizer's Torcetrapib Tanks" - In Vivo, 1 December, 2006.

Despite spending approximately $9 billion annually on R&D and holding one of the industry's largest pipelines, the pharma is still struggling to find its next round of blockbusters, while current top sellers like Lipitor near patent expiration.

Differing Views On Antibody's Market Potential

Fernandez and Anderson differ strongly on how big a loss tanezumab would be for Pfizer if it ends development of the antibody entirely. Saying "we now assume that the drug will not move forward," Fernandez has subtracted global sales projections for tanezumab from its Pfizer guidance through 2016. He had projected the drug yielding $525 million in sales revenues that year.

Anderson did not include tanezumab in his revenue projections for Pfizer, citing the drug's risky profile and low consensus expectations for sales.

"The commercial case for tanezumab in OA pain has long baffled us," he wrote. "Tanezumab would have to be given as an injection, and would compete in a category (pain) filled with many existing medicines the vast majority of which are given orally, Naturally, the product seemed destined to be a last-line therapy for OA pain. Its utility in other pain-causing diseases seems similarly challenged."

Anti-NGFs, several of which are in development with tanezumab the most advanced, are seen as offering a promising new category of analgesics, a class dominated by NSAIDS that have poor side-effect profiles and opioids, which carry the risk of dependence and substance abuse potential (Also see "A Painstaking Approach: Can Anti-NGFs Give Relief To Pharma Pipeline Woes?" - Pink Sheet, 17 May, 2010.).

A new analgesic for osteoarthritis could face an appealing market opportunity - an estimated 80 million patients in the world's seven largest markets. Pfizer projects there will be 250 million chronic pain patients by next year, with only one in five treated adequately by currently available therapies.

The pharma had hoped to produce final data from the Phase III trials in osteoarthritis by next year, with a possible launch of tanezumab occurring in 2012. Acquired when Pfizer purchased Rinat Neuroscience Corp. for $500 million in cash in 2006, tanezumab has posted compelling data in Phase II trials ([See Deal]). Pfizer also obtained another Phase III candidate, bapineuzimab for Alzheimer's disease, in that deal.

Substantial Pain Reduction Seen In Phase II

At an American College of Rheumatology meeting in 2008, Pfizer presented Phase II data from a 16-week, placebo-controlled trial of 444 osteoarthritis patients who received a five-minute IV infusion of tanezumab every eight weeks. In two different dosage groups, roughly 75 percent of treatment-drug participants experienced a 50 percent decrease in knee pain, compared to 26 percent of placebo arm patients. Further, more than 30 percent in both tanezumab arms experienced a 90 percent pain reduction (Also see "Pfizer’s Tanezumab For Pain Turns Heads At Rheumatology Meeting" - Pink Sheet, 31 October, 2008.).

In that trial, the most common adverse events were headache (8.9 percent), upper respiratory tract infection (7.3 percent) and numbness (6.8 percent).

There are at least four other anti-NGF compounds in clinical development for pain indications presently. These include Ortho-McNeill-Janssen Pharmaceuticals' JNJ-42160443, in Phase II, and Sanofi-Aventis' REGN-475. Both are said to be 18 to 24 months behind the development curve for tanezumab.

Also in the race are a pair of Phase I compounds, MedImmune's MEDI-578 and Abbott's PG110. Both are being investigated in osteoarthritis.

-Joseph Haas (j.haas@elsevier.com)

Future Appears Grim For Pfizer's Tanezumab With Ostearthritis Trial Stopped

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