PD-1 agonist induces ‘little excitement’ in rheumatoid arthritis

November 21, 2022

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Emery P. Abstract L03. Presented at: ACR Convergence 2022; Nov. 11-14, 2022; Philadelphia (hybrid meeting).

Emery reports affiliations with Abbvie, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly & Co., Galapagos NV, Gilead Sciences, Novartis, Pfizer, Roche, and Samsung Bioepis.

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PHILADELPHIA — A new therapy targeting human apoptosis-inducing protein-1 showed activity in rheumatoid arthritis with an attractive safety profile, according to a presenter at the ACR Convergence 2022.

“Our objective was to test the efficacy of perezolimab (Eli Lilly) in moderately or severely active rheumatoid arthritis,” Paul Emery, MD, from the University of Leeds, in the UK, said those present.

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“On a collective level, this drug clearly works,” Paul Emery, MD, told the attendees.

According to Emery, peresolimab is a humanized immunoglobulin G1 monoclonal antibody that stimulates human programmed cell death protein 1 (PD-1). The researchers hypothesized that perezolimab’s binding to PD-1 could stimulate physiological immunosuppressive pathways to restore immune homeostasis.

Paul Emery

“It gives us an opportunity to tell you about other operations that have been a little bit exciting,” Emery said.

The current phase 2a, double-blind, placebo-controlled, randomized clinical trial included 101 patients with RA. Among these patients, 49 received perezolimabi 700 mg intravenously, 25 received perezolimabi 300 mg, and 24 received placebo. Treatment was given every 4 weeks.

The group was more than 80% female, with a mean age at baseline of 51.7 years, a mean disease duration of 10 years at baseline, and a mean DAS28-CRP score at baseline of 5.9. In addition, patients presented with an average of six swollen joints and objective evidence of joint inflammation on MRI at baseline.

“The admission criteria are pretty standard,” Emery said.

The primary endpoint results showed significant improvements from baseline to week 12 in DAS28-CRP score in both peresolimabi 700 mg (P <.001) and 300 mg (P = .017) groups compared to placebo.

“There are advantages for both doses of the active drug,” Emery said. “A primary endpoint was achieved for the superiority of this drug over placebo.” On a collective level, this drug clearly works.”

CDAI score was also significantly improved compared to placebo in the mean 700 mg (P <.001) and 300 mg (P = .008) groups.

Meanwhile, the 700 mg dose produced a significant improvement compared to placebo in terms of ACR20 response (P <.05).

Emery added that the number of swollen joints has also “improved significantly”.

Although overall patient assessment scores showed “steady improvement,” there was no separation between treatment and placebo for these patient-reported variables, according to Emery.

Regarding patients who had experience with disease-modifying anti-rheumatic drugs vs. Those who were DMARD naïve, Emery noted “no loss of response” in the trial group.

“Normally, you would expect naïve patients to do better,” he said. “There was a trend toward better response in targeted synthetic and biologic DMARDs [experienced] patients.”

Emery then pointed out an important conclusion that can be drawn from this result.

“More intolerant patients are doing well,” he said.

Safety data through 24 weeks showed only two treatment-emergent adverse events in the low-dose peresolimab group and five in the high-dose group, according to Emery. He added that no treatment was discontinued in the high-dose group at any point in the study.

“There is no side effect that is higher at a high dose.” [group compared with the] lower dose or placebo,” Emery said. “There is no dose effect.”

If there was a caveat to the wider applicability of the findings, it is that the patient population is small. That said, Emery found both the efficacy and safety data to be encouraging, especially in treatment-experienced patients.

“This may be more effective or certainly beneficial for resistant patients, for whom we have a very high unmet need in RA,” Emery said. “They represent the first clinical evidence that agonist receptor antagonists may be an effective method for treating rheumatic diseases.”

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