Results From Two Phase 3 Trials of Bimekizumab Unveiled

Doug Brunk

June 25, 2020

Results from two late-breaking phase 3 trials of bimekizumab, an investigational interleukin-17A and IL-17F inhibitor, showed that most patients with moderate to severe psoriasis achieved clearance at week 16 and maintained their clinical response at 1 year.

"The rapid and lasting skin clearance observed in the majority of patients in both clinical studies demonstrate bimekizumab's strong potential to deliver across three key areas: speed, depth and durability," Kristian Reich, MD, said in an interview during the virtual annual meeting of the American Academy of Dermatology.

Bimekizumab selectively inhibits IL-17A and IL-17F, two key cytokines that drive inflammation and tissue damage across multiple diseases. In BE VIVID, Dr. Reich, of the Center for Translational Research in Inflammatory Skin Diseases at the University Medical Center Hamburg-Eppendorf (Germany), and colleagues randomized 567 patients with moderate to severe psoriasis to bimekizumab 320 mg every 4 weeks (Q4W), ustekinumab (45/90 mg weight-based dosing at baseline and week 4, then every 12 weeks), or placebo (Q4W through week 16 then bimekizumab 320 mg Q4W). Coprimary endpoints were a Psoriasis Area and Severity Index (PASI) of at least 90 and an Investigator Global Assessment (IGA) response of 0 or 1. Secondary/other outcomes included PASI 100 at week 16; PASI 90, IGA 0/1, and PASI 100 at week 52; and safety. (Ustekinumab is an IL-12 and IL-23 antagonist.)

The mean age of patients was 46 years and 72% were male. The researchers found that the proportion of patients who achieved PASI 90 and an IGA of 0/1 was higher in the bimekizumab arm at week 16 (85.0% and 84.1%, respectively), compared with those in the ustekinumab arm (49.7% and 53.4%) and those on placebo (4.8% and 4.8%; P < .001 for all associations). In addition, 58.6% of patients in the bimekizumab arm achieved PASI 100, compared with 20.9% of those in the ustekinumab arm and none of those on placebo.

At week 52, patients in the bimekizumab arm achieved PASI 90, IGA 0/1, and PASI 100 response rates of 81.6%, 77.9%, and 64.2%, respectively, compared with 55.8%, 60.7%, and 38.0% of those in the ustekinumab arm. Over 52 weeks, incidence of serious treatment-emergent adverse events was 6.1% with bimekizumab arm, compared with 7.4% in the ustekinumab arm. Four deaths occurred (two in the bimekizumab arm, and one each in the ustekinumab and placebo arms), all considered unrelated to treatment. The most common reported adverse events in the bimekizumab arm through week 52 were nasopharyngitis (21.8%), oral candidiasis (15.2%), and upper respiratory tract infections (9.1%).

"The rapid and lasting skin clearance observed in the majority of patients treated with bimekizumab provide support for inhibiting IL-17F, in addition to IL-17A, to inhibit the IL-17 pathway," Dr. Reich said. "This can make a meaningful difference for people living with psoriasis." He added that the results of the head-to-head study of bimekizumab with secukinumab (an IL-17A antagonist) are expected later this year. "It will be very interesting to see if the marked differences in treatment effect seen in the BE VIVID study remain when comparing to an IL-17."

In BE READY, a pivotal phase 3, randomized, withdrawal study, investigators led by Kenneth Gordon, MD, randomized 435 patients with moderate to severe psoriasis 4:1 to receive 320 mg Q4W or placebo, and followed them for 16 weeks. In a second part of the study, patients who had achieved at least a PASI 90 response at week 16 were rerandomized to receive continuous bimekizumab at two different dosing regimens: 320 mg Q4W or 320 mg every 8 weeks (Q8W), or to be withdrawn from treatment (placebo Q4W), and followed through week 56. Relapse was defined as a PASI score of less than 75 from week 20.

The mean age of patients was 44 years and 72% were male. At week 16, the proportion of patients who achieved a PASI 90 and an IGA of 0/1 was greatest in the bimekizumab arm (90.8% and 92.6%, respectively), compared with those on placebo. In addition, 68.2% of patients in the bimekizumab arm achieved PASI 100 at week 16, compared with only 1.2% of those on placebo (P < .001 for all associations). In the second part of the study, the researchers found that 86.8% of patients who received continuous bimekizumab 320 mg Q4W maintained PASI 90 at week 56, compared with 91% who were switched to bimekizumab 320 mg Q8W, and 16.2% of patients who were withdrawn from the trial.

"The speed of response and the number of patients who achieved clearance are extremely high, especially in a phase 3 trial," Dr. Gordon, professor and Thomas R. Russell Family Chair of Dermatology at the Medical College of Wisconsin, Milwaukee, said in an interview. "However, the most surprising aspect may be the impressive maintenance of response in patients, even those who were treated with every-8-week dosing in the maintenance phase. While it is possible that there are some patients who may benefit from more frequent dosing in the long term, the possibility of every-8-week dosing would be a tremendous benefit for patients."

As in the BE VIVID trial, the most frequently reported adverse events with bimekizumab between week 16 and week 56 in BE READY were nasopharyngitis (10.4% in the Q4W arm vs. 23% in the Q8W arm), oral candidiasis (11.3% Q4W vs. 9% Q8W), and upper respiratory tract infections (11.3% Q4W vs. 8% Q8W). The incidence of serious treatment-emergent adverse events with bimekizumab was 4.7% in the Q4W arm and 3% in the Q8W arm versus 3.8% in the placebo arm at week 56.

"The results from BE READY demonstrate that bimekizumab has the potential to deliver rapid and lasting skin improvement for psoriasis patients," Dr. Gordon said. "The findings also support the hypothesis that inhibiting IL-17F, in addition to IL-17A, may be more effective in suppressing inflammation in suppressing inflammation in psoriasis than IL-17A inhibition alone."

Both studies were funded by UCB Pharma. Dr. Reich disclosed that he has served as adviser and/or paid speaker for and/or participated in clinical trials sponsored by companies that include UCB. Dr. Gordon disclosed that he has received honoraria and/or research support from companies that include UCB.

American Academy of Dermatology (AAD) 2020 Annual Meeting.

This article originally appeared on MDEdge.com.

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