Novartis' BTK inhibitor beats placebo in dermatology trial, lining up another potential indication

Novartis’ BTK inhibitor remibrutinib reduced disease activity in patients with the skin disease hidradenitis suppurativa, potentially setting up another indication for the pharma to tackle with the BTK inhibitor.

Remibrutinib is being tested in the phase 2b trial in patients with mild to severe hidradenitis suppurativa—a skin disease that causes painful lumps to form in areas where the skin rubs together. The trial is testing six total investigational treatments, including remibrutinib in cohort D, against placebo over 16 weeks.

A total of 66 patients participated in cohort D, split between a 25-mg dose and 100 mg. The results were presented at the American Academy of Dermatology (AAD) Saturday.

Novartis’ offering met the primary endpoint, with patients on both doses achieving a greater than 50% reduction in abscess and inflammatory nodule count and no increase in draining tunnels compared with baseline. The rate of response was higher with the lower 25-mg dose, with 73% of patients achieving the endpoint, compared to 49% for the 100-mg dose.

On the exploratory efficacy results, remibrutinib also beat placebo in achieving 50%, 70% and 90% clearance of abscessed and inflammatory nodule counts. Just over 36% of patients on the lower dose achieved 90% clearance, compared with 15% of the high dose group and 8% of the placebo cohort.

The therapy also had a greater effect on abscess and inflammatory nodules and draining tunnel at Week 16 compared to placebo, and skin pain response was better.

As for safety, there were reports of grade 3 and 4 adverse events in the remibrutinib arm, totaling five patients, but placebo also had four grade 3s. Both treatment groups and placebo had high rates of grade 1 events, with 14 reporting them in the 25-mg group, 11 in the 100-mg group and 26 on placebo. The serious adverse events reported were acute pancreatitis in the 25-mg group, hypertensive crisis in the 100-mg group and testicular abscess in the placebo group. The lower-grade adverse events were primarily infections such as upper respiratory infections.

One patient in the low dose group had liver enzyme elevations, which can be indicative of liver damage, but the case was asymptomatic and deemed not related to study treatment.

Liver toxicity issues have troubled other BTK inhibitors in earlier trials, so this result adds to evidence that remibrutinib may not have the same issue.

Remibrutinib was well tolerated, and the adverse events were largely comparable to the placebo group, the AAD presenters summarized in the slides. Treatment discontinuations due to adverse events were also uncommon, although just 80% of patients completed treatment, which the investigators chalked up to patients’ own decisions.

Novartis has a pile of indications lined up for remibrutinib, with the lead indication of chronic spontaneous urticaria, aka hives, nearing a regulatory filing. A phase 3 readout last summer showed that patients taking the drug experienced a significant change from baseline in their weekly urticaria activity score, a measure of hives and itching. Other indications include food allergy, multiple sclerosis and other types of hives.

The Swiss pharma also markets Xolair, the current market leader for hives, with Roche. If remibrutinib ultimately manages to secure approval, the company could hang on to the market that others are trying to break into.

Sanofi and Regeneron appeared close late last year with Dupixent, but ultimately were rejected with the FDA asking for further efficacy data.