Roche’s MabThera/Rituxan Demonstrates Superior Efficacy in Second Positive Phase III Trial for Pemphigus Vulgaris

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On June 13, Roche announced positive top-line data from the Phase III PEMPHIX study evaluating MabThera/Rituxan (Rituximab) for the treatment of pemphigus vulgaris (PV).

PEMPHIX is a randomized, double-blind, double-dummy, active-controlled, parallel-arm, multicenter Phase III study conducted in adult patients with moderate-to-severe active pemphigus vulgaris (PV) who require 60–120 mg/day of oral prednisone (or equivalent). The study evaluated the efficacy and safety of rituximab compared with standard-of-care therapy (mycophenolate mofetil [MMF]).

In the study, patients were randomly assigned to two treatment groups: (1) the rituximab group, receiving 1000 mg of intravenous rituximab on Day 1 and Day 15, with repeated dosing on Day 168 and Day 182, along with matched placebo for MMF; (2) the MMF group, receiving oral MMF at a dose of 2 g once daily from Day 1 to Week 52, along with matched placebo for rituximab. The primary endpoint was the proportion of patients achieving steroid-free sustained complete remission at Week 52 of treatment (defined as no disease activity assessed by the Pemphigus Disease Area Index [PDAI] and no use of steroid therapy for at least 16 consecutive weeks). Secondary endpoints included cumulative oral corticosteroid dose, number of disease flares, time to achieve sustained complete remission, time to disease flare, and health-related quality of life.

The results demonstrated that the study met its primary endpoint: a higher proportion of patients in the rituximab group achieved sustained complete remission without the need for steroid therapy compared to the MMF group. Furthermore, the study also met all secondary endpoints. The adverse events observed in this study were consistent with those reported in previous clinical trials of rituximab for other autoimmune indications. The full data from this study will be presented at an upcoming medical conference and submitted to regulatory authorities worldwide, including the U.S. FDA.

Pemphigus vulgaris (PV) is a rare, severe, and potentially life-threatening autoimmune disease characterized by progressive, painful blistering of the skin and mucous membranes, accounting for approximately 80% of pemphigus cases. Pemphigus comprises a group of autoimmune disorders caused by autoantibodies produced by B cells in the immune system that attack desmosomal proteins connecting epidermal skin cells. When these connections are disrupted, the cells separate from one another, leading to skin separation and blister formation. Globally, it is estimated that approximately 3 per 100,000 individuals are diagnosed with this condition.

MMF is an unapproved therapy for pemphigus vulgaris (PV) that has been recognized as standard of care. In June 2018, Mabthera/Rituxan was approved in the United States and the European Union as the first biologic therapy for the treatment of PV, marking the first major advance in the clinical management of PV in over 60 years. This approval was based on data from the Phase III Ritux 3 clinical study. The recently published PEPHIX study data will provide additional clinical evidence supporting the efficacy of Mabthera/Rituxan in the treatment of PV.

MabThera/Rituxan is a therapeutic monoclonal antibody that targets and binds to the CD20 antigen on the surface of both normal and malignant B cells, subsequently mobilizing the body’s natural defenses to attack and destroy the marked B cells. To date, Rituxan has been approved for the treatment of four autoimmune diseases in adults, including: rheumatoid arthritis, granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA), and pemphigus vulgaris (PV).

Recently, the US FDA accepted and granted priority review to the supplemental application for Mabthera/Rituxan in combination with glucocorticoids (GCC) for the treatment of GPA and MPA in children aged 2 years and older. If approved, this will become the first pediatric indication for Mabthera/Rituxan.

GPA and MPA are two rare forms of vasculitis, and there are currently no FDA-approved medications for treating pediatric patients. For adult patients with GPA and MPA, Rituxan in combination with GCC is the only FDA-approved treatment regimen.

References:

1、Phase III PEMPHIX study showed that Roche’s Mabthera/Rituxan (rituximab) is superior to standard of care in achieving sustained remission in patients with pemphigus vulgaris

2、FDA grants priority review to Roche’s Mabthera/Rituxan (rituximab) in children with two rare blood vessel disorders