乌鸦传媒

SAN DIEGO -- An investigational Bruton's tyrosine kinase (BTK) inhibitor significantly improved hidradenitis suppurativa (HS) disease status in a randomized, placebo-controlled trial reported here.

More than 70% of patients had at least a 50% reduction in the abscess and inflammatory nodule (AN) count after 16 weeks of treatment with remibrutinib 25 mg twice daily. Increasing the dose did not improve efficacy, as about half of patients on 100 mg of remibrutinib twice daily met response criteria. In contrast, a third of patients allocated to placebo responded by 16 weeks.

Remibrutinib also reduced draining nodules and skin pain and had a safety profile similar to placebo, reported Alexa B. Kimball, MD, of Beth Israel Deaconess Medical Center in Boston, at the meeting.

"This is wonderful news for our HS community in that remibrutinib showed higher response rates versus placebo in patients with moderate to severe HS at week 16," said Kimball. "You can see it in all of the [endpoint] computations that we look at. You can see it in the tunnel panels and in skin pain, as well. It was well tolerated. The AEs [adverse events] were as expected, mostly mild to moderate. I think we are very much looking forward to seeing how this mode of action goes forward."

During a discussion that followed the presentation, an unidentified member of the audience asked Kimball how the results of remibrutinib compared with currently available therapies for HS, acknowledging the absence of randomized comparisons.

"The overall results are in line with what we're seeing with the most effective therapies we have, but it's way too early to make any distinguishing comparisons," she said. "What I think is most exciting is that it is a different mechanism of action that we feel like is perhaps complementary to some of our other therapies. As we try to push the field forward and make sure that we can get patients to higher levels of efficacy, being able to potentially combine therapies or tailor the therapy to their stage in the process of the disease is really an opportunity, and we're very excited about that."

Remibrutinib had a rapid onset of action, associated with clear evidence of improvement within 2 to 4 weeks, Kimball said in response to another question.

Better known as therapy for hematologic malignancies, BTK inhibitors' B-cell targeting is relevant to HS, as studies have demonstrated the presence of B cells in HS lesions, with as a central signal transduction pathway. Remibrutinib is under investigation in several immune-mediated inflammatory conditions, including chronic spontaneous urticaria (CSU) and multiple sclerosis. A recent phase III report demonstrated safety and efficacy in more than 600 patients with CSU.

Kimball reported findings from a placebo-controlled study with a platform design, which has allowed testing of multiple different agents in parallel sequencing over the past 5 years.

"This is very elegant in a disease like HS, where we don't understand the biology as well as we would like and there are a lot of different cytokines involved," she said. "This becomes a wonderful bedside-to-bench interaction to figure out what parts of the biology are important."

The phase IIb multicenter, randomized trial involved 77 patients with moderate to severe HS, with 66 allocated to two different dose levels of remibrutinib and 11 randomized to placebo, with 50 pooled placebo patients from multiple cohort studies used for comparison. The primary endpoint was the proportion of patients who met criteria for the simplified Hidradenitis Suppurativa Clinical Response (sHiSCR) scoring system, defined as at least a 50% reduction in the total AN count at 16 weeks.

By use of non-responder imputation, the primary analysis showed a sHiSCR response rate of 72.7% with the lower dose of remibrutinib, 48.5% with the higher dose, and 34.7% for the pooled control patients. Bayesian estimates were 72.3%, 48.5%, and 34.9%.

Analysis of patients who achieved the best responses showed that 42.4% of patients treated with 25 mg of remibrutinib had 75% improvement from baseline (HiSCR 75), as compared with 27.3% and 18.4% of the high-dose and placebo groups. Rates of 90% improvement (HiSCR 90) were 36.4%, 15.2%, and 8.2%.

The draining-tunnel count decreased by 55.6% with the lower dose of remibrutinib, 43% with the higher dose, and 10.2% with placebo. The higher dose of remibrutinib had a greater impact on skin-pain response at 16 weeks, with 57.1% achieving at least a 30% decrease in NRS skin pain and at least a 1-point decrease, as compared with 44.4% for the lower remibrutinib dose and 30.4% with placebo.

Grade 3/4 AEs occurred in two patients in each of the remibrutinib groups. Serious AEs occurred in one patient in each remibrutinib arm (acute pancreatitis, hypertensive crisis). No patient discontinued treatment with remibrutinib 25 mg as compared with two in the remibrutinib 100 mg group and two in the placebo group.

Comment