Bimekizumab phase 3 data reflect rapid, durable response

The BE VIVID and BE READY studies of bimekizumab in psoriasis show strong, long-lasting patient responses and no unexpected safety signals.

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“Dermatologists and patients with psoriasis are looking for a treatment that delivers speed, depth and durability,” says Kenneth Gordon, M.D., professor and chair of dermatology at the Medical College of Wisconsin and principal BE READY investigator.

The phase 3 data demonstrate bimekizumab’s strong potential to deliver in these areas, adds principal BE VIVID investigator Kristian Reich, M.D., Ph.D. He is professor for translational research in inflammatory skin diseases, Institute for Health Services Research in Dermatology and Nursing, University Medical Center Hamburg-Eppendorf, Germany.

Bimekizumab is a second-generation IL-17 inhibitor, says Dr. Reich. Ixekizumab and secukinumab block IL-17A, and brodalumab inhibits the IL-17A receptor.

“We believe IL-17A and F are the main drivers of the psoriatic disease process,” he notes.

Dr. Gordon adds that the IL-17F protein is considerably more present in psoriatic plaques than IL-17A.

“So while IL-17A might have a little more physiological activity, both of these molecules are considered significant for the treatment of psoriasis,” he says.

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“Theoretically, if you block F in addition to A, hopefully you should see even higher levels of response,” notes Dr. Reich.

Indeed, the 567-patient BE VIVID trial produced some of the highest response levels ever recorded. At week 16, the proportions of patients randomized to bimekizumab who achieved Psoriasis Area and Severity Index (PASI) 90 and 100 were 85% and 58.6%, respectively. The corresponding figures for ustekinumab were 49.7% and 20.9%. Also at week 16, 84.1% and 53.4% of patients on bimekizumab and ustekinumab reached investigator global assessment (IGA) scores of zero or one with at least a two-point improvement over baseline.

Additionally, 76.9% of bimekizumab-treated patients reached PASI 75 by week four, versus 15.3% of ustekinumab-treated patients. At week 52, an approximately 25-point difference in PASI 90 and 100 rates between bimekizumab and ustekinumab persisted.

The BE VIVID study spotlights bimekizumab’s speed and durability of response, says Dr. Reich.

“There is no longer a trade-off when it comes to onset and maintenance of response with this IL-17 inhibitor,” he adds. “You’re getting the best of both worlds by blocking IL-17F in addition to A.”

In BE READY, investigators randomized 435 patients with moderate-to-severe-psoriasis to bimekizumab every four weeks or placebo. At week 16, investigators rerandomized PASI 90 responders to bimekizumab every eight weeks, every four weeks or placebo through week 56.

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Week 16 PASI 90, PASI 100 and IGA 0/1 rates among bimekizumab-treated patients were 90.8%, 68.2% and 92.6%, respectively, versus 1.2% in all three metrics for placebo. More impressive, says Dr. Gordon, are week four PASI 75, 90 and 100 rates of76%, 45% and 19%.

Week 56 PASI 90 rates for four- and eight-week dosing were 86.8% and 91%, respectively; the corresponding figures for IGA 0/1 were 86.8% and 90%. Conversely, 16.2% of patients rerandomized to placebo maintained PASI 90 by week 56.

“But this is not a rapid return of disease with bimekizumab therapy,” says Dr. Gordon. Median time to relapse (defined as PASI 75) was 28 weeks.

In both studies, bimekizumab was well tolerated. The most common bimekizumab-related adverse events included nasopharyngitis and oral candidiasis, the latter of which was generally mild-to-moderate and an expected effect of IL-17 inhibitors. No BE READY patients stopped therapy due to candidiasis, while five did so in BE VIVID.

Dr. Gordon says, “Data from both BE READY and BE VIVID suggest that bimekizumab may allow patients to have a very high likelihood of robust responses in their psoriasis and even clearance of their disease. This happens quickly and can be maintained effectively while having very good tolerability.”

References:

Kristian Reich,MD, PhD, Kim A Papp MD, Andrew Blauvelt MD, et al. “Efficacy and safety of bimekizumab in patients with moderate-to-severe plaque psoriasis: results from BE VIVID: a 52-week phase 3, randomized, double-blinded, ustekinumab- and placebo-controlled study,” American Academy of Dermatology VMX. June 13, 2020.

Kenneth Gordon MD, Peter Foley MD, James Kruger MD, et al. “Efficacy and safety of bimekizumab in patients with moderate-to-severe plaque psoriasis: results from BE READY, a 56-week phase 3, randomized, double-blinded, placebo-controlled study with randomized withdrawal,” American Academy of Dermatology VMX. June 13, 2020.

Disclosures:

Dr. Reich has served as advisor and/or paid speaker for and/or participated in clinical trials sponsored by AbbVie, Affibody, Almirall, Amgen, Avillion, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Centocor, Covagen, Dermira, Eli Lilly, Forward Pharma, Fresenius Medical Care, Galapagos, GSK, Janssen-Cilag, Kyowa Kirin, LEO Pharma, Medac, Merck Sharp & Dohme, Miltenyi Biotec, Novartis, Ocean Pharma, Pfizer, Regeneron, Samsung Bioepis, Sanofi, Sun Pharma, Takeda, UCB Pharma, Valeant and XenoPort.

Dr. Gordon has received honoraria and/or research support from AbbVie, Almirall, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Dermira, Eli Lilly, Janssen, Novartis, Pfizer, Sun Pharma and UCB Pharma.