No Relief For Pfizer As It Shuts Down Additional Tanezumab Trials

Safety concerns require Pfizer to scupper two additional studies of its Phase III tanezumab, casting doubt on an entire class of new pain drugs.

In a blow to its pipeline that casts doubt on an entire class of novel pain drugs, Pfizer said it would end two more sets of clinical trials on tanezumab, an inhibitor of nerve growth factor upon which the company halted Phase III trials for osteoarthritis last month.

Pfizer said Monday, July 19 it will comply with a Food & Drug Administration request to suspend Phase II trials of tanezumab for lower back pain and diabetic peripheral neuropathy, based on adverse effects noted in the osteoarthritis trial. On June 23, the FDA requested that Pfizer halt that Phase III trial, and the company said a day later it would comply (Also see "Future Appears Grim For Pfizer's Tanezumab With Ostearthritis Trial Stopped" - Pink Sheet, 24 Jun, 2010.).

The end of the Phase II trials bodes ill for tanezumab, the most advanced of several candidates thought to block pain by inhibiting nerve growth factor. A protein crucial for nerve cell growth and maintenance, NGF mediates pain sensations in the body.

Pfizer said it has suspended recruitment and dosing in the three trials but will continue research and trials on tanezumab for cancer and pancreatitis. A Pfizer spokesman said it will continue to work with the FDA to determine the most appropriate cause of action for other tanezumab trials.

Many had high hopes that tanezumab's approval would usher in a new class of remedies for chronic pain, potentially supplanting non-steroidal anti-inflammatories or opiates in the market for some indications. Pfizer acquired Rinat Neuroscience for an estimated $500 million in 2006 largely for Rinat's anti-NGF and Alzheimer's programs, while others such as Johnson & Johnson, Sanofi-Aventis and Abbott have acquired and developed anti-NGF candidates in earlier stages of development (Also see "A Painstaking Approach: Can Anti-NGFs Give Relief To Pharma Pipeline Woes?" - Pink Sheet, 17 May, 2010.).

Competing programs are now likely to fall under increased scrutiny for adverse effects similar to those that halted trials on tanezumab. A Pfizer spokesman did not elaborate on the results except to say that the Phase III tests showed a worsening of osteoarthritis in a relatively small percentage of the more than 7,000 patients who received infusions of the drug.

The reasons for the safety signal weren't immediately clear. Leerink Swann analyst Seamus Fernandez told "The Pink Sheet" last month that when chronic pain is eased, increased stresses on joints could lead to deterioration. Bernstein Research's Tim Anderson wrote in a research note that some tanezumab patients also reported numbness, dizziness and edema.

One silver lining for Pfizer: the safety concerns didn't prompt the FDA to ask the company to discontinue tanezumab trials in other areas. Decision Resources analyst Natalie Taylor pointed out that osteoarthritis wasn't an exclusion criterion in either of the two newly suspended trials, and that it has a high incidence of co-morbidity with both lower back pain and diabetic peripheral neuropathy. In metastatic bone cancer patients, by comparison, Taylor said "safety concerns become less important when patients are fighting for quality of life."

Broader market implications

Prior to the regulatory requests, Decision Resources estimated that Pfizer could tally about $1.5 billion in peak year sales and pegged a 2012 launch for tanezumab in the osteoarthritis indication. The bulk of revenues would come from osteoarthritis, with cancer accounting for $250 to $500 million.

But if tanezumab ever comes to market, it's likely to generate far less revenue than previously expected. Taylor called it "highly doubtful" that Pfizer will be able to reformulate the drug to overcome safety issues, and said those concerns will likely result in "a class-wide phenomenon" of disappointing data.

As such, FDA's decision could have implications for a number of other industry players from diversified giants Johnson & Johnson and Abbott to smaller biotechs. J&J has a Phase II subcutaneous NGF inhibitor being studied for osteoarthritis, lower back pain and diabetic peripheral neuropathy as well as cancer, bladder, and neuropathic pain, while Sanofi and Regeneron are co-developing an intravenous infusion.

A spokesman for Regeneron said the company is "trying to follow and understand the clinical hold situation" around tanezumab, but said the company hasn't yet been asked to suspend any trials. Regeneron recently completed a Phase II study on its drug for osteoarthritis and is researching other indications.

At an investor meetinglast week, Regeneron senior vice president for clinical development and regulatory affairs Peter Powchik told an audience that the company had furnished relevant data to the FDA and that its clinical program was ongoing. Unlike tanezumab, Regeneron's drug acts exclusively on NGF instead of binding to multiple neurotrophins, potentially leading to fewer off-target side-effects.

But Decision Resources' Taylor predicts the safety warning will affect all anti-NGF candidates. "If [regulators] see any potential worsening [of existing conditions], they'll make them stop there," she said.

Tanezumab's disappointing performance also affects Pfizer's overall strategy. Its patent on the blockbuster Lipitor (atorvastatin) is slated to expire in June 2011, and the company is spending billions on research and development in search of compounds to make up the lost revenue. The company also received discouraging Phase III data for an Alzheimer's disease drug, Dimebon (latrepirdine), in early March, the same week it pulled oncology drug Mylotarg (gemtuzumab ozogamicin) from the market (Also see "Prospects For Pfizer/Medivation's Dimebon Dashed By Phase III Flop" - Pink Sheet, 3 Mar, 2010.). Pfizer will likely discuss its R&D strategy during its second quarter earnings call August 3. -- Paul Bonanos ( [email protected] )