Painkillers Win Panel’s Backing to Continue Patient Studies
Pfizer Inc. (PFE), Johnson & Johnson (JNJ), and Regeneron Pharmaceuticals Inc. won the backing of a U.S. advisory panel to continue development of a class of experimental painkillers that have been linked to joint failure.
The Food and Drug Administration advisers voted 21-0 today in Silver Spring, Maryland, that the benefits of enhanced pain relief outweigh the risks of the so-called anti-nerve growth factor drugs. The FDA isn’t required to follow the panel’s advice.
Studies on the class of drugs, once expected by analysts to generate as much as $11 billion a year, were halted in 2010 after the joint issues were reported. Trials for osteoarthritis and back pain, among other chronic conditions, are on hold while a study in cancer pain is ongoing.
“There’s significant risk but there are probably patient populations where there will be significant benefit,” Lenore Buckley, professor of internal medicine and pediatrics at Virginia Commonwealth University School of Medicine in Richmond and chairwoman of the panel, said during the meeting.
The drugs block nerve growth factor, a protein causing certain nerve cells to grow, according to the National Institutes of Health. The panel suggested drugmakers screen patients and take certain safety precautions to continue development.
The FDA reviewed 355 joint-replacement cases from previous trials involving 401 joints. The agency determined patients experienced 83 cases of rapidly progressing osteoarthritis where bone and cartilage deteriorated and 30 cases of osteonecrosis, which is bone death caused by poor blood supply, Nona Colburn, a clinical reviewer with the FDA’s Center for Devices and Radiological Health who conducted one of the agency’s two independent reviews, told the panel.
Committee members agreed the number of incidents are uncommonly high.
Use in conjunction with nonsteroidal anti-inflammatory painkillers increased the likelihood of joint failure, the FDA found.
Pfizer, poised to be the front runner in osteoarthritis applications, halted trials in June 2010 for its compound tanezumab, and stopped remaining studies for other conditions a few weeks later. Pfizer, the world’s largest drugmaker, is based in New York.
The agency also asked New Brunswick, New Jersey-based J&J and Tarrytown, New York-based Regeneron Pharmaceuticals Inc. (REGN) to halt development of the painkillers fulranumab and REGN475, respectively, in December 2010. Regeneron is working with Paris- based Sanofi (SAN) on the drug, also known as SAR164877.
London-based AstraZeneca Plc (AZN) voluntarily ended early-stage research on a similar medicine, MEDI578, at the same time.
Abbott Laboratories (ABT)’ anti-NGF painkiller, ABT-110, completed a Phase 1 trial. The Abbott Park, Illinois-based company didn’t participate in the advisory panel meeting and is following developments, said Raquel Powers, a spokeswoman, in an e-mail. Three phases of clinical trials usually are required for U.S. regulatory approval of a new drug.
Pfizer said it wants to begin a final-phase osteoarthritis study by late this year or early 2013. Bob Rappaport, director of FDA’s division of anesthesia, analgesia and addiction products, asked the committee whether companies should have to go back and conduct earlier-stage trials over again.
The drugmakers should resume development by conducting earlier-stage trials because they didn’t know about the risk of joint failure before, said David Blumenthal, a panel member and assistant professor of medicine at Case Western Reserve University in Cleveland, Ohio.
“There is sufficient evidence of harm that we continue this sort of moratorium on this research or we just kind of start over as if there had been a signal in preclinical studies with different enrollment criteria,” Blumenthal said.
Pfizer and the other companies will have to bring a proposal to the FDA to seek clearance to resume studies, Rappaport said.
The panel’s discussion “underscored the unmet need of patients with chronic pain conditions,” Pfizer said in a statement after the vote. The company said it looked forward to working with the agency.
Osteoarthritis, which is often associated with aging, is the most common joint disorder, according to the National Institutes of Health. “Wear and tear” on a joint breaks down cartilage and the bones rub together causing pain and stiffness, according to the NIH website.
A Pfizer study of 450 patients with osteoarthritis of the knee found tanezumab reduced pain 45 percent to 62 percent compared with a 22 percent reduction with placebo, according to an Oct. 2010 article in the New England Journal of Medicine.
Patients were given an injection of the drug in the beginning of the study and again after eight weeks. They were able to use the “rescue” painkiller acetaminophen.
“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 nonsteroidal anti-inflammatory painkillers such as Advil and aspirin and narcotics have side effects involving the gastrointestinal tract, heart and kidneys, Lane said.
Pfizer, J&J and Regeneron recommend patients refrain from chronic use of nonsteroidal anti-inflammatory painkillers and use lower doses to treat osteoarthritis than previously used in trials to continue studies, Ned Braunstein, head of regulatory affairs for Regeneron told the panel.
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