Phase 2 Clinical Trial on Pemphigus

A recent phase 2 clinical trial found positive outcomes in patients with pemphigus, a rare and potentially life-threatening autoimmune disease. The study focused on the use of rilzabrutinib, which is an oral, reversible, covalent Bruton tyrosine kinase (BTK) inhibitor, to manage pemphigus. The results of this clinical trial were published in the recent issue of Journal of Investigative Dermatology.

Pemphigus is a serious condition to treat and often requires long-term therapy to control the symptoms and minimize the exposure to corticosteroids that can have significant side effects. However, this phase 2 trial demonstrated that rilzabrutinib could offer both rapid and sustained effectiveness with well-tolerated safety profiles in patients.

During the study period, adults who were 18 to 80 years old with moderate-to-severe pemphigus vulgaris/foliaceus (PV/PF) were randomized into two groups:

• One group received rilzabrutinib.
• The other group received a placebo.

The participants in the rilzabrutinib group were administered 400 mg of the drug twice daily along with corticosteroids at a dose of 0.5 mg/kg/d, over a period of 37 weeks.

The primary endpoint was to achieve a complete remission (CR) from week 29 to 37 with a reduced corticosteroid dose, which was not statistically significant. The secondary endpoints hinted at the potential benefits of rilzabrutinib therapy, which included:

• Reduced corticosteroid usage
• Prolonged CR duration
• A faster time to first CR

The results of this study emphasized the well-tolerated nature of rilzabrutinib and the need to consider alternative analyses. A prespecified sensitivity analysis evaluated a minimal corticosteroid dose of ≤5 mg/d and included all observations and patients that provided encouraging results, which supports BTK inhibition as a potential therapeutic strategy for pemphigus. While the primary endpoint did not reach statistical significance using the traditional criteria, the sensitivity analysis highlighted the potential of rilzabrutinib in pemphigus management with reduced corticosteroid exposure.

The results of the phase 2 trial represent a significant step forward in pemphigus research and offer hope to patients grappling with this challenging autoimmune condition. Further research, including larger-scale trials and long-term follow-up, is imperative to enhance crucial understanding of the efficacy and safety of rilzabrutinib in pemphigus management.

Reference

Murrell, D. F., Caux, F., Patsatsi, A., Hagino, O., Rudnicka, L., Vassileva, S., Uzun, S., Ye, J., Yen, K., Arora, P., Gourlay, S. G., Joly, P., & Werth, V. P. (2024). Efficacy and Safety of Rilzabrutinib in Pemphigus: PEGASUS Phase 3 Randomized Study. In Journal of Investigative Dermatology. Elsevier BV. https://doi.org/10.1016/j.jid.2024.02.023