Rilzabrutinib Shows Positive Results in Phase 2b for Pemphigus

Bruce Jancin

July 22, 2020

Rilzabrutinib, a novel oral reversible Bruton's tyrosine kinase inhibitor, delivered rapid control of pemphigus disease activity accompanied by markedly reduced need for systemic corticosteroids in the phase 2b BELIEVE-PV trial, Dedee F. Murrell, MD, said at the virtual annual meeting of the American Academy of Dermatology.

Moreover, in sharp contrast to the standard first-line treatments for pemphigus – rituximab (Rituxan) and high-dose corticosteroids – the treatment-emergent adverse events that arose with 6 months of rilzabrutinib in BELIEVE-PV were uniformly mild to moderate and transient, added Dr. Murrell, professor of dermatology at the University of New South Wales and head of the department of dermatology at St. George University Hospital, Sydney.

The phase 2b BELIEVE-PV trial was a small, 24-week, open-label study that included six patients with newly diagnosed pemphigus and nine others with relapsing pemphigus. The primary endpoint was control of disease activity, defined as no new lesions appearing and established lesions beginning to heal. This was achieved in 9 of 15 patients (60%) at 4 weeks and in 13 patients by week 12. Meanwhile, the mean daily dose of prednisone fell from 21 mg at baseline to 6 mg at 24 weeks.

The mean score on the Pemphigus Disease Area Index (PDAI) dropped by 79% from a baseline of 15.5. Ten of 15 subjects improved to a PDAI of 0 or 1 – clear or almost clear skin – by week 24. The complete remission rate, defined as an absence of both new and established lesions while on no or a very low dose of prednisone, was 40% at week 24.

Treatment-emergent adverse events consisted of nausea in four patients, dizziness in two, and abdominal distension in two, all of which were grade 1 or 2.

Based upon these favorable results, the pivotal phase 3, double-blind, international PEGASUS trial is underway, led by Dr. Murrell. The trial will enroll 120 pemphigus patients, randomized to rilzabrutinib at 400 mg twice daily or placebo on top of background steroid tapering.

Rilzabrutinib is also in earlier-stage clinical trials for the treatment of immune thrombocytopenia.

Dr. Murrell reported serving as a consultant to Principia Biopharma, sponsor of the BELIEVE-PV and PEGASUS trials, and has received institutional research grants from numerous pharmaceutical companies.

SOURCE: Murrell DF. AAD 2020 LBCT.

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