WASHINGTON — Patients with moderate-to-severe plaque psoriasis attained durable complete and near-complete responses for more than a year with a dual inhibitor of interleukin (IL)-17, data from a randomized trial showed.
Almost all patients who initially had 90%-100% improvement (PASI90/100) with bimekizumab maintained the responses during 60 weeks of follow-up. Similarly, patients who switched from placebo to bimekizumab and attained PASI90/100 responses maintained the status long term.
Across all doses evaluated in the study, 80%-100% of responding patients remained in response at 60 weeks, Andrew Blauvelt, MD, of Oregon Medical Research Center in Portland, reported at the American Academy of Dermatology (AAD) meeting.
“We have not seen responses like this,” Blauvelt said. “When you look at the PASI90 responders, who were responders from the beginning, we have very high levels of maintenance of that response and many of them are at PASI100. We had a consistent safety profile, as would be expected with an IL-17 blocker. These results really support the view that IL-17A and IL-17F blockade as useful in psoriasis.”
Data from the trial set a new standard for psoriasis drugs in development, said Jeffrey Weinberg, MD, of Mount Sinai Medical Center in New York City. Speaking at an AAD forum on biological therapy for psoriasis, Weinberg noted that 60% of patients treated with a higher dose of bimekizumab attained PASI100 during the first 12 weeks of the trial.
“This is the first time you will see this,” said Weinberg. “First we reached 40%, then 50%, and now we’re at 60% of patients with PASI100.”
Alluding to the high rates of PASI90 responses, Weinberg added, “As we go through life we keep saying ‘If we could only get to 100.’ Well, we’re getting closer and closer as you can see here.”
In his concluding remarks, Weinberg seconded Blauvelt’s view that the results validate dual neutralization of IL-17A and IL-17F as a new therapeutic approach, which might result in “slightly improved efficacy in this population with sustained safety.”
Blauvelt reported findings from long-term follow-up in the randomized, phase II BE ABLE 1 trial, which involved 250 patients with chronic plaque psoriasis allocated to one of four doses of bimekizumab or to placebo. The results showed that 46%-79% of bimekizumab-treated patients attained PASI90 responses at 12 weeks (the primary endpoint). No patient in the placebo group had a PASI90 response.
During BE ABLE 2, patients who attained PASI90 responses remained on their assigned dose of bimekizumab, and in those who did not reach PASI90, improvement continued with treatment at a higher dose. Patients originally assigned to 320 mg every 4 weeks (the recommended dose) stayed on that dose, and patients originally randomized to 480 mg Q4W continued at treatment with the 320-mg dose. Placebo-treated patients switched to bimekizumab 160 mg Q4W. Follow-up continued for an additional 48 weeks for a total of 60 weeks of treatment and follow-up.
Blauvelt reported the response data in two ways: as observed and by the more conservative nonresponder imputation (NRi) methodology. During the initial 12 weeks of randomized treatment, 46%-79% of patients treated with bimekizumab achieved PASI90 responses. During the additional 48 weeks of follow-up, 80%-100% of patients maintained those responses by NRi. In the as-observed analysis, 100% of patients maintained PASI90 responses.
Analyses of patients who initially attained PASI90 responses, and subsequently improved to PASI100, showed that 69%-83% of PASI100 responses were maintained by NRi and 80%-96% as observed. Additionally, responding patients who had Investigator Global Assessment scores of 0-1 (clear/nearly clear) maintained the scores in 78%-100% of cases by NRi and 97%-100% as observed.
Every patient randomized to the 320-mg dose of bimekizumab, and continued at that dose, had an absolute PASI score <2 at 60 weeks, said Blauvelt. Placebo-treated patients switched to bimekizumab had rapid improvement in absolute PASI scores that were maintained for as long as 48 weeks, similar to patients originally randomized to active therapy.
The incidence of treatment-emergent adverse events (TEAEs) was similar to prior experience with IL-17 inhibitors, and investigators saw no evidence of dose-related increases in TEAEs, said Blauvelt. The most frequent TEAEs were oral candidiasis and nasopharyngitis (13% each). No serious TEAEs occurred in more than one patient.
The study was sponsored by UCB.
Blauvelt disclosed relevant relationships with AbbVie, Aclaris Therapeutics, Akros Pharma, Allergan, Almirall, Amgen, Boehringer Ingelheim, Celgene, Dermavant Sciences, Dermira, Eli Lilly, Galderma, Genentech, GlaxoSmithKline, Janssen-Ortho, LEO Pharma, Meiji Seika Pharma, Novartis, Merck, Pfizer, Purdue Pharma, Regeneron, Sandoz, Sanofi, Sienna Biopharmaceuticals, Sun Pharmaceutical, UCB, Valeant Pharmaceuticals, and Vidac Pharma.