The investigational monoclonal antibody mirikizumab performed more robustly against placebo overall — and the interleukin (IL)-17 inhibitor secukinumab at key endpoints — for treatment of moderate-to-severe psoriasis, according to new long-term OASIS-2 trial data.
Both doses of mirikizumab in the international, double-blind trial achieved improvements in Psoriasis Area and Severity Index (PASI) scores in larger numbers of participants at week 52 than secukinumab (Cosentyx), with low adverse event rates.
If approved, mirikizumab, which binds the p19 subunit of IL-23, would join three other IL-23 drugs already marketed in the United States for moderate-to-severe psoriasis, said OASIS-2 lead investigator Kim Papp, MD, PhD, from Probity Medical Research in Waterloo, Canada.
But Papp feels larger studies “will be necessary to put these data into perspective,” he said during a presentation at the 29th European Academy of Dermatology and Venereology (EADV) Congress, held virtually this year because of the pandemic.
“Probably the most important takeaway here is that we may have another option to choose from,” Papp told Medscape Medical News. “People tend to think we have an adequate stable of treatment options, and I would argue we do not.”
“There are variations over time that occur in terms of an individual’s biological response, and the consequence is that nothing we have works for everyone, and nothing we have works forever,” he added.
Psoriasis biologics “are increasingly competent compared to medications we had even 5 or 10 years ago…but they still don’t satisfy all our needs, so we do need to keep replenishing our stock.”
The multicenter trial included 1465 patients who were randomly split into four groups. Subcutaneously, one group received 250 mg of mirikizumab every 4 weeks, and then 250 mg of the drug every 8 weeks starting at week 16. Another group received 250 mg of mirikizumab every 4 weeks and then 125 mg every 8 weeks starting at week 16.
The third group received 300 mg of secukinumab weekly for 4 weeks and then every 4 weeks starting at week 4. The last group received placebo every 4 weeks, and then 250 mg of mirikizumab every 4 weeks from week 16 to 32 and every 8 weeks thereafter.
Primary endpoints measured the percentage of patients achieving a static Physician’s Global Assessment (sPGA) of 0 or 1, with an improvement of at least 2 points from baseline; and the proportion of patients with PASI 90 at week 16 compared with placebo.
Major secondary endpoints were PASI 75 and PASI 100 compared with placebo at week 16; an sPGA of 0 or 1 and PASI 90 non-inferiority compared with secukinumab at week 16; and sPGA of 0 or 1, PASI 90, and PASI 100 superiority compared with secukinumab at week 52.
More than 91% of participants completed all 52 weeks in the trial. Mirikizumab met primary endpoints compared with placebo and major secondary endpoints vs secukinumab at week 16 (P < .001). PASI 90 and sPGA (0,1) response rates far exceeded placebo for both 250 mg mirikizumab (74.4% and 79.7%, respectively) and secukinumab (72.8% and 76.3%, respectively).
At week 52, major secondary endpoints for both mirikizumab doses were superior to secukinumab (all P < .001). PASI 90 was achieved by 81.4% of 125 mg and 82.4% of 250 mg mirikizumab patients vs. 69.4% of secukinumab patients; sPGA (0,1) by 83.1% of 125 mg and 83.3% of 250 mg mirikizumab patients vs. 68.5% of secukinumab patients; and PASI 100 by 53.9% of 125 mg and 58.8% of 250 mg mirikizumab patients vs. 42.9% of secukinumab patients.
Treatment-associated adverse effects were similar across all treatment groups and study periods. The most common were nasopharyngitis, upper respiratory tract infection, headache, back pain, and arthralgia. But serious adverse effects were minimal, Papp said. One death occurred in a mirikizumab patient from acute myocardial infarction, which was deemed unrelated to the study drug.
Myrto Georgia Trakatelli, MD, PhD, from Aristotle University of Thessaloniki in Greece, said the results indicate that dermatologists “should not be afraid to use” mirikizumab long-term if it is approved by the US Food and Drug Administration.
“Sometimes patients use many treatments for a long time and all of a sudden, they stop working,” Trakatelli told Medscape Medical News. “A new biologic is always welcome because we do see patients not responding to other treatment.”
But Trakatelli said “a point that troubled me in the study” was that mirikizumab was compared with an IL-17 inhibitor “instead of a molecule targeting IL-23, such as guselkumab [Tremfya], for example.”
“I would have liked to see a head-to-head comparison with a molecule that blocks the same target,” said Trakatelli, chair of the EADV Education Committee.
Papp countered that “there are various reasons for running comparator studies.” Secukinumab, he said, “was the market leader and was widely used, so it makes sense that one is going to compare against a product as the market lead.”
“Not to say there won’t be future studies” in which mirikizumab is compared “head to head with IL-23s,” Papp added.
But larger patient numbers and longer treatment times are still needed with mirikizumab “to characterize the level of response, duration of response, and any adverse event profiles,” Papp stressed.
“One study does not a drug make,” he said. “It’s just exciting that we still have things to offer. This is an important example, and of course opportunity, for patients.”
The trial was funded by Lilly. Papp has disclosed financial relationships with AbbVie, Amgen, Astellas, Valeant, Baxalta, Baxter, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Coherus, Dermira, Forward Pharma, Galderma, Genentech, GlaxoSmithKline, Janssen, Kyowa Kirin, LEO Pharma, Lilly, Medimmune, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi Genzyme, Stiefel, Sun Pharma, Takeda, and UCB. Trakatelli is a speaker for Novartis.
29th European Academy of Dermatology and Venereology (EADV) Congress: Abstract 3061. Presented October 29, 2020.
Maureen Salamon is a freelance health journalist based in London and New Jersey.