Biotech Values

[DewDiligence]

Tanezumab May Have Worked ‘Too Well’ to Work

[This is one hypothesis for what caused PFE’s drug to be placed on FDA clinical hold in June (#msg-51634760), which led PFE to curtail the clinical program in July (#msg-52431429). As recently as Jan 2010, PFE considered Tanezumab one of its five most-promising late-stage drug candidates (#msg-45428806), so a restart of the program would indeed be quite bullish.]

http://blogs.wsj.com/health/2010/09/29/did-pfizers-experimental-arthritis-drug-work-too-well

›By Peter Loftus
September 29, 2010, 5:10 PM ET

Can a pain reliever work too well?

Some researchers are suggesting that an experimental Pfizer drug may have liberated arthritis sufferers to such a degree that they became more physically active — and that the subsequent wear and tear on their joints led to joint replacement surgery.

It’s just a theory at this point, but if borne out, it raises the possibility that the drug, tanezumab, may get another chance. Clinical trials were suspended earlier this year, at the FDA’s request, when some patients’ arthritis worsened to the point of needing joint replacement. (The company later suspended studies of the same drug for chronic low back pain and diabetes-related nerve pain, but said it would continue studying it for certain other conditions including cancer pain.)

Some Wall Street analysts, who once viewed the drug as having blockbuster sales potential, soured on its prospects after the trial suspensions. Pfizer is now working with regulators to determine the next steps for tanezumab, which could take several months to resolve, a spokesman says.

The drug made people feel “better than [they] ever felt before, and I have a feeling they just overused their joints,” Nancy Lane, a rheumatologist and bone-health specialist at UC Davis Health System in Sacramento and co-author of a new study on tanezumab, tells the Health Blog. She suggests the drug could still play a role as long as doctors “counsel patients not to overuse their joints.”

The research, published today in the New England Journal of Medicine, was a phase 2, proof-of-concept study conducted in 2006-07. The 450-patient study showed that tanezumab relieved knee pain when compared to a placebo. (Some patients experienced adverse events such as headache and upper respiratory tract infection.)

Pfizer says there were no indications in that study of the kind of joint failure that led to the suspension of subsequent trials. The NEJM article says that in a phase 3 study suspended earlier this year, 16 users experienced progressively worsening osteoarthritis associated with a form of bone damage known as necrosis, which required total joint replacements. The company says no causal relationship between the drug and these adverse events has been established.

In an accompanying editorial, John Wood, a researcher with the University of London, writes the joint failure “was most likely caused by excessive wear and tear in the absence of joint pain. Pain has an important role in the avoidance of self-harm, but chronic inflammatory pain has generally been considered to be wholly undesirable.” The tanezumab study “suggests that a complete quenching of pain in patients with osteoarthritis may not necessarily be a good thing,” he writes.

Lane says she has seen this pain-masking situation before, including with the nonsteroidal anti-inflammatory drug (NSAID) indomethacin.

This fall Pfizer plans to release data — via a medical meeting or journal — from three of its phase 3 trials of tanezumab in osteoarthritis patients. That information may help shed light on whether the problem was over-active patients or some other issue.

Wood serves as a visiting professor at Baylor College of Medicine, a post funded by Pfizer. The 2006-07 trial was supported by Rinat Neuroscience, which is now a unit of Pfizer, and Pfizer funded editorial support for the study published in NEJM.‹