FDA advisory committees will begin hearings on drug aimed at osteoarthritis pain
For 15 years, Pfizer has been developing a drug it hopes will be a treatment for osteoarthritis pain. It has tested the drug in more than 40 clinical trials and has a long list of patients who have gotten substantial relief.
The drug, tanezumab, which is delivered by injection every two months, doesn’t cause the gastrointestinal problems or slight stroke risk of some arthritis pain relievers, and isn’t addictive, like opioids.
But tanezumab can, in rare cases, accelerate cartilage loss around joints. Called rapid progressive osteoarthritis, this side effect struck about 3% of the patients in recent clinical trials.
Wednesday morning, two Food and Drug Administration advisory committees will begin a day-and-a-half of hearings on tanezumab and decide whether they think the benefits outweigh the risks.
More than 31 million Americans suffer from osteoarthritis, which causes painful swelling and stiffness of the joints as cartilage degenerates. Many can get sufficient help from physical therapy, weight loss, cognitive behavioral therapy, and readily-available drugs like ibuprofen, naproxen or Celebrex.
But for others, like Maureen Elias, 43, of Oakton, Virginia, outside Washington, D.C., those don’t provide enough relief.
Elias, now a veteran advocate, suffered spinal injuries while in the Army in the mid-2000s, leading to a lifelong battle with arthritis.
When physical therapy left her hurting even more and Tylenol and Aleve stopped helping, she was prescribed opioids. But “it was too hard to parent while using them,” said Elias, whose children are now 10, 16 and nearly 18. The opioid withdrawal was unexpected and horrible, she said.
“Now I just suck it up. The military mentality,” she said, chuckling.
To limit the pain, she has had to forgo being active. “It really kind of cheats myself and my family.”
First therapy in a decade
Tanezumab, which would be the first totally new therapy for arthritis in more than a decade, is aimed at the 11 million arthritis patients like Elias for whom other drugs haven’t worked well, said Peter Park, medical engagement lead for Pfizer, which is co-developing the drug along with Eli Lilly and Co.
“The unmet need is huge,” he said. “They need options.”
Elias agrees. She said she would take her chances on a drug like tanezumab, hoping it would reduce her pain and enable her to live a more active life.
Several arthritis specialists said they also see a need to add tanezumab to their patients’ treatment options, though they would recommend it to only a limited number and would have in-depth conversations before prescribing.
Dr. Amanda Nelson, an associate professor of medicine at the University of North Carolina at Chapel Hill, worries that rapidly progressing osteoarthritis could occur more often in the “real world” than in the carefully controlled environment of clinical trials.
And it might happen in a joint that wasn’t problematic already – disabling patients even more than they already were.
If a patient “were trying to put off replacement of their right knee and ended up needing a left shoulder replacement, I mean, that’s really the thing that I think makes me extremely hesitant to use this,” Nelson said.
The pain reduction patients see with tanezumab is comparable to the relief people typically get with Tylenol or other so-called non-steroidal anti-inflammatories, she said. Early trials of tanezumab that used higher doses of the drug provided more relief, but also caused more cases of rapidly progressing osteoarthritis.
Still, said Nelson, who contributes to patient education efforts for the Arthritis Foundation, there’s a need for better treatments for arthritis pain.
“It’s a serious disease, we have very few options for it, with lots of patients and a lot of pain. And this is really the only sort of novel promising therapy that it’s very far along,” she said.
Dr. Jeffrey Katz, director of the Orthopedic and Arthritis Center for Outcomes Research at Brigham and Women’s Hospital in Boston, said there’s no doubt in his mind that the FDA should approve tanezumab.
“Having a new medication to fill that space is most welcome,” he said. “It’s terrific to have product development in this area.”
But Katz said he doesn’t want to dismiss the risk. “Patients and their physicians are going to have to have careful discussions about this medication, because it’s a serious side effect.”
Hip and knee X-rays suggested
Pfizer and Lilly have agreed to follow patients taking the drug if tanezumab is approved. The companies also have suggested patients get baseline X-rays of hip and knee joints before starting the drug, and then repeat scans after a year to make sure those joints aren’t deteriorating.
If the FDA decides those repeat X-rays should come sooner than a year, the companies would be okay with that, too, said Ken Verburg, a Pfizer senior vice president.
Research also has suggested that taking a non-steroidal anti-inflammatory along with tanezumab could increase risk, so patients would need to be counseled not to take both at once, Verburg said.
Patients who develop rapidly progressive osteoarthritis will be told to stop taking tanezumab. At that point, their joints will not deteriorate further although the damage is permanent, he said.
Tanezumab could potentially be used to treat chronic pain from other conditions, likely one of the reasons the companies have been pursuing its approval for so long. Studies have explored using the drug to treat lower back pain, neuropathic pain, visceral pain and a late-stage study in metastatic bone pain is expected to be completed later this year.
“Yes, we are interested in and we feel like there could be a substantial benefit to patients with other chronic pain conditions if we get tanezumab to them,” Verburg said. “But our priority right now is osteoarthritis and of course our success in osteoarthritis will drive us in certain directions with other chronic pain conditions.”
Verburg said it’s pure speculation at this point, but he thinks rapidly progressive osteoarthritis may not occur as often among people who do not already have joint damage.
The side effect might be caused by overusing a faulty joint, he said. As tanezumab reduces pain, it could encourage people to become more active, exacerbating the joint problem and causing rapidly progressive osteoarthritis, Verburg said, quickly adding that has not been scientifically confirmed.
Tanezumab, a so-called monoclonal antibody, appears to work by blocking nerve growth factor, a protein involved in regulating nerve cells. Blocking the growth factor prevents stimulation of pain-sensing nerves, though it won’t make touching a hot stove any less painful, Verburg said.
At the end of Thursday’s hearing, the FDA advisory committees will vote on whether they think tanezumab’s benefits justify its risks. Then, it’s up to FDA officials to decide when and whether to approve the drug for use in arthritis patients.
“So far, we’ve been really pleased with the overall safety and tolerability profile,” said Verburg, who has led Pfizer’s development effort for a decade-and-a-half. “If not for this joint safety event, you have to kind of think that tanezumab would have been available to patients long before now. Unfortunately, that’s not the case.”
Contact Karen Weintraub at email@example.com.
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