U.S. regulators asked an advisory panel whether Pfizer Inc. and Johnson & Johnson, the two biggest U.S. makers of health-care products, should resume human trials on a class of experimental painkillers linked to joint failure.
Studies on the class of drugs known as anti-nerve growth factor drugs, designed to treat osteoarthritis and chronic back pain, were halted in 2010 after the joint problems were reported. All trials are stopped except those in cancer pain.
The medicines, once expected by analysts to generate as much as $11 billion a year, will be considered by the Food and Drug Administration’s outside advisers on March 12. The FDA staff also asked the panel to weigh whether plans are needed to monitor risks during the trials, and if nonclinical studies should be conducted, according to a document posted on the agency website today.
“Having a public discussion of this topic at an advisory committee meeting is unusual in that these products are still in the investigational new drug phase of development and are not already approved or under review as new drug applications,” Bob Rappaport, director of FDA’s division of anesthesia, analgesia and addiction products, wrote in the staff report.
In contrast to other FDA staff documents, today’s report doesn’t contain detailed analyses of the safety signals that patients experienced during clinical trials.
At issue is whether the adverse events were evidence of osteonecrosis, or bone death caused by poor blood supply, or if patients’ osteoarthritis naturally progressed to a point where bone and cartilage deteriorated.
The FDA conducted an adjudication of the safety reports and determined both osteonecrosis and osteoarthritis are associated with the drugs’ use, according to a separate document posted on the agency’s website.
Pfizer, poised to be the frontrunner in osteoarthritis applications, halted trials in June 2010 for its compound tanezumab, and stopped remaining studies for other conditions a few weeks later.
The agency next asked New Brunswick, New Jersey-based J&J and Tarrytown, New York-based Regeneron Pharmaceuticals Inc. to halt development of the painkillers fulranumab and REGN475/SAR164877, respectively, in December 2010. Regeneron is working with Paris-based Sanofi.
Other Experimental Painkillers
London-based AstraZeneca Plc. voluntarily ended early-stage research on a similar medicine, medi578, at the same time.
Abbott Laboratories’ anti-NGF painkiller, ABT-110, completed a phase 1 trial. The Abbott Park, Illinois-based company won’t participate in the advisory panel meeting and is following developments, said Raquel Powers, a spokeswoman, in an e-mail.
New York-based Pfizer wants to begin a final-phase osteoarthritis study by late this year or early 2013.
A company study of 450 patients with osteoarthritis of the knee found tanezumab reduced pain 45 percent to 62 percent compared to a 22 percent reduction with placebo, according to an Oct. 2010 article in the New England Journal of Medicine.
“The treatment options for patients with painful osteoarthritis of the knee are inadequate,” Nancy Lane, the study’s lead author and director of the Center for Aging at the University of California, Davis School of Medicine in Sacramento, wrote in the journal article.
Commonly used non-steroidal anti-inflammatory painkillers and narcotics have side effects affecting the gastrointestinal tract, heart and kidneys, Lane said.
Pfizer, J&J and Regeneron have suggested risk plans to resume studies that include limiting or excluding NSAID use and possibly capping the dose at a lower amount than the highest one used in clinical trials or limiting dosing if a joint-related event occurs.