Novel TYK2 inhibitor may be a ‘game changer’ for psoriasis
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MAUI, Hawaii — A novel TYK2 inhibitor may provide clinicians with another treatment option along the janus kinase pathway in patients with severe psoriasis, according to a presentation at the 2020 Rheumatology Winter Clinical Symposium.
“This is causing a lot of excitement, this BMS oral TYK2 inhibitor,” George Martin, MD, of Dr. George Martin Dermatology Associates in Hawaii, told attendees of BMS-986165 (Bristol-Myers Squibb). “When you look at the JAK/STAT pathway and what molecules they affect, you look at TYK2 and you see IL-12 and IL-23, as well as interferon alpha and beta. They are all affected if, in fact, you block TYK2.”
TYK2 signaling mediates fewer cytokines compared with JAK 1-3 inhibitors, according to Martin. He added that these are important cytokines that drive psoriasis.
While he presented on a broad range of topics pertaining to the rheum-derm continuum, Martin focused on data from a phase 2 study conducted by Papp and colleagues in patients with severe psoriasis. “They selected a wide range of your standard psoriasis patients,” Martin said. “A lot of body surface area, and there was prior biologic use in roughly half of them. These patients had a lot of disease.”
The study included 45 participants receiving placebo and 44 participants receiving 3 mg active therapy with BMS-986165 every other day, 44 receiving 3 mg once a day, 45 receiving 3 mg twice a day, 45 receiving 6 mg twice a day and 44 receiving 12 mg once a day.
Results showed that almost 75% of the cohort reached PASI 75 response, while half reached PASI 90 response, according to Martin. “This is a blowaway slide,” he said. “But check out the results for PASI 100. About 25% of patients were totally clear.”
Safety data showed three serious adverse events in the active therapy arm. The drug was also associated with acne, particularly in patients who received the 6 mg and 12 mg doses.
Martin said that the researchers also looked at how the drug impacted hemoglobin, NK cell count, neutrophil count and total cholesterol. “When you look at it, there was no impact on any of them,” he said. “If you talk to the scientists who whipped up this molecule, they are really trying to distance themselves from the regular JAK inhibitors.”
In addition to the potential improvements in psoriasis, Martin believes that BMS-986165 may also have utility in invasive bowel disease.
“This is really exciting,” Martin said. “We can’t wait to get our hands on this. I think it is going to be a game changer.” – by Rob Volansky
Reference:
Martin G. State of the Art 2020: What’s new in dermatology? An update for rheumatologists. Presented at RWCS Annual Meeting; Feb. 12-15, 2020; Maui, Hawaii.
Disclosure: Martin reports being on the scientific advisory boards of Abbvie, Celgene, Dusa/Sun, Galderma, Horizon, Janssen, Leo, Ortho/Bausch Health and Pfizer; consulting for Aqua, Celgene, Dusa/Sun, Lily, Ortho/Bausch and Pfizer; and being a speaker for Dusa/Sun, Ortho/Bausch and Pfizer.