Positive signs for brepocitinib, not the other kinases tested
The results showed that though brepocitinib worked in HS, the other two novel compounds did not appear to have beneficial effects. Just over half (52%) of the 52 patients treated with brepocitinib achieved an HiSCR at 16 weeks, compared with around one-third of those given placebo, PF-06650833, or PF-06826647.
A similar benefit was seen in terms of reduction in flares for brepocitinib but not the other agents, although there was no difference between them all in terms of NPRS30 pain reduction.
“We’ve been able to test three different modalities. This tells us some things about the pathophysiology for HS, which is a very profoundly intensive inflammatory process,” which, Dr. Kimball said, “may require multiple modalities of action to get it under control.” In addition, these “general modalities seem to safe and well tolerated,” she added.
Take-homes for practice and future research
“While it is disappointing that two of the drugs tested did not clearly demonstrate efficacy, it is very possible that these mechanisms of action may be successful targets in the future as new dosing strategies and drugs targeting these pathways are developed,” Dr. Sayed said.
A case in point, he added, was that “adalimumab did not meet treatment endpoints at a dose of 40 mg every other week, but clearly has made a major impact at 40 mg weekly.”
The bottom line is that “both secukinumab and beprocitinib demonstrated efficacy over placebo and are likely to be helpful for a significant number of patients with HS,” Dr. Sayed said. “Hopefully, we’ll see head-to-head trials and more data regarding proportions of patients with deeper responses using criteria such as HiSCR75 and HiSCR90.”
Moreover, “having a larger number of drugs with a range of mechanisms of action is extraordinarily helpful given how difficult the disease can be to manage. We will hopefully continue to see creative approaches and further successes in the current wave of phase 1, 2, and 3 trials that are already underway.”
The SUNSHINE and SUNRISE studies were funded by Novartis Pharma AG, Basel, Switzerland. The phase 2A study Dr. Kimball presented was sponsored by Pfizer.
Dr. Kimball disclosed ties to both Novartis and Pfizer and acts as a consultant and investigator to AbbVie, Bristol-Myers Squibb, Janssen, Eli Lilly, Novartis, and UCB. She is an investigator for Incyte and AnaptysBio; acts as a consultant to Bayer, Boehringer Ingelheim, Ventyz, Moonlake, Lily, Concert, EvoImmune, Sonoma Bio, and Sanofi; receives fellowship funding from Janssen, and serves on the Board of Directors for Almirall.
Dr. Patel had no conflicts of interest to disclose. Dr. Sayed is the director of the HS Foundation, a nonprofit organization, and has acted as an adviser or consultant to, speaker for, and received research funding from multiple drug companies including AbbVie, ChemoCentryx, Incyte, InflaRx, Novartis, and UCB.
A version of this article first appeared on Medscape.com.