What’s up in the osteoarthritis drug pipeline

TORONTO – The barren pharmacologic landscape in osteoarthritis today is reminiscent of rheumatoid arthritis 30 years ago: few drugs, limited effectiveness, Philip G. Conaghan, MBBS, PhD, observed at the OARSI 2019 World Congress.

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Dr. Philip Conaghan

“Not only have things not improved during my time in osteoarthritis-land, they’ve gotten worse. We’ve lost therapies,” said Dr. Conaghan, professor of musculoskeletal medicine at the University of Leeds (England) and director of the Leeds Institute of Rheumatic and Musculoskeletal Medicine.

Specifically, opioids are now shunned because of the ongoing epidemic of addiction and a belated recognition that opioids are not a good option for pain relief in OA patients who want to have active lives. And acetaminophen has fallen by the wayside in light of recent evidence of lack of effectiveness: “It’s what our patients have been telling us for a long period of time,” he noted at the meeting sponsored by the Osteoarthritis Research Society International.

But change is in the air.

“I think we’ve got some things coming that look promising. What do I think will be the fastest to get to market? The peripheral nerve modulators look to me like the ones closest to going forward,” according to the rheumatologist, who provided an overview of the OA drug development pipeline, organized by treatment target.

Nerves

“Nerves as a treatment target in OA is a hot area. We’ve seen quite a slew of products recently looking at this. I think it’s a really fascinating area to play in: looking at how we modulate peripheral nociceptive pain,” Dr. Conaghan continued.

Tanezumab, an inhibitor of nerve growth factor, demonstrated very good pain relief and improvement in physical function in a phase 3 trial, although the occurrence of rapidly progressive OA in a subset of patients has bedeviled the drug development program. The hope is that a new subcutaneous drug delivery system coupled with careful patient pretreatment screening will mitigate the problem.

Tanezumab’s efficacy has contributed to a new understanding of the nature of pain in OA.

“I know I’m going to upset some people, but if you think central sensitization is the biggest driver of pain, I’d have to argue that the tanezumab program is the biggest single argument against that, since tanezumab is a large monoclonal antibody that doesn’t cross the blood-brain barrier and yet it has some of the best pain responses that we’ve seen,” Dr. Conaghan said.

Another peripheral nerve modulator, known for now as CNTX-4975, exhibited dose-dependent improvement in knee OA pain in the 175-patient, phase 2b TRIUMPH trial (Arthritis Rheumatol. 2019 Mar 19. doi: 10.1002/art.40894). CNTX-4975, which is delivered by intra-articular injection, is a synthetic form of capsaicin specific to pain nociceptors within the joint. Other sensory fibers remain unaffected.