Clinicians have 'reason for optimism' in novel osteoarthritis therapies
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A number of compounds and therapeutic approaches moving through the pipeline may soon enrich treatment paradigms for osteoarthritis, according to a presenter at the 2020 Congress of Clinical Rheumatology-East.
“It is a time where there is so much excitement and so much activity in this space,” Nancy E. Lane, MD, director for the Center for Musculoskeletal Health and principal investigator of the NIH-funded Program on Sex Differences in Musculoskeletal Diseases Across the Lifespan at the UC Davis School of Medicine, said of the new drugs in her presentation. “Hopefully, we soon may see them in our practice.”
Lane said many rheumatologists encourage patients to lose weight and exercise more as a way of fending off the progression of osteoarthritis. “But then we will work our magic with analgesics, anti-inflammatories and then injections, as needed,” she said.
She reviewed a number of therapies currently in development, some of which are intra-articular, some systemic.
Lorecivivint (Samumed), a Wnt pathway inhibitor, has moved into phase 3 trials after phase 1 studies showed reduced pain compared with placebo and phase 2 demonstrated improvements in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain and function.
“We will know pretty soon its efficacy based on signs and symptoms,” Lane said. “We hope the sponsor will look at structure modification.”
With regard to stem cell therapy, Lane discussed preclinical data for the protein kartogenin, which is currently in phase 1b studies as an intra-articular injection in patients with OA. “Those result should be available pretty soon,” she said. “That compound is able to differentiate mesenchymal stem cells to chondrocytes to make bone.”
A novel approach to OA treatment involves senescence, according to Lane. “As we age, certain cells in different tissues do not divide, and they do not die, but become senescent,” she said, and added that when that happens, the cells release a sap.
According to Lane, understanding the nature of this sap may hold clues to OA treatment. “Scientists thought that since osteoarthritis is a disease of aging, maybe the cells in the cartilage are senescent,” she said.
With that in mind, a senolytic agent UBX0101 (Unity Biotechnology) is currently in phase 2b trials. While Lane acknowledged this approach has not shown the capacity to be an analgesic for OA pain, further investigation may be warranted.
Another drug that is “quite far along” but unfamiliar to many rheumatologists is sprifermin, a recombinant human fibroblast 18 drug, according to Lane. Results of the phase 2b, 5-year FORWARD trial of sprifermin did not appear to change joint pain parameters, but there may still be hope. “We will have to see,” she said.
A novel approach to analgesic management pertains to nociceptive pain. Specifically, addressing nerve growth factor (NGF)-mediated pain pathways using the intravenous NGF drug tanezumab (Pfizer) has shown promise in clinical trials, according to Lane. The injection differentiated from placebo in pain parameters and showed a “rapid onset of action and a long duration of action,” she said.
A 2.5 mg subcutaneous dose of tanezumab shows the most promise, Lane added.
Tropomyosin receptor kinase A inhibition is currently being investigated in a phase 2 study in moderate to severe knee OA. While the approach showed efficacy in animal studies, it has yet to break through in human trials. “I don’t know that they are going to work,” Lane said.
“Unexpected” positive results have been reported with canakinumab (Ilaris, Novartis), Lane said. “Giving it every 3 months significantly reduced the number of joint replacements. We will look at this to slow the progression of osteoarthritis.”
Given all of these potential avenues of osteoarthritis treatment, Lane believes the future is bright for management of this disease. “There is reason for optimism for our patients,” she said.
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Lane NE. Osteoarthritis Update. Presented at: Congress of Clinical Rheumatology-East annual symposium; September 10-13, 2020 (virtual meeting).
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