Staying Ahead of Biosimilar Competition, Roche's Rituxan Shows Superiority in Rare Autoimmune Skin Disease

Roche announced results from its Phase III PEMPHIX trial evaluated MabThera/Rituxan (rituximab) compared to mycophenolate mofetil (MMF) in adults with moderate to severe pemphigus vulgaris (PV). MabThera/Rutixan showed superiority to MMF.

Pemphigus vulgaris is a rare, serious and potentially life-threatening disease. It is marked by progressive and painful blistering of the skin and mucous membranes. MMF is the most commonly used treatment for PV although it has not been approved by regulators for it but is the recommended treatment in my published treatment guidelines.

MabThera/Rituxan was approved for PV by the U.S. Food and Drug Administration (FDA) in June 2018 and by the European Commission in March 2019. It was the first biologic therapy approved for PV. The approvals were based on results from the Roche-supported Ritux 3 clinical trial. This most recent trial, PEMPHIX, provides more evidence of the drug’s effectiveness for PV.

PEMPHIX is a Phase III, randomized, double-blind, double-dummy, active-comparator, parallel-arm, international, multicenter study designed to evaluate the efficacy and safety of the drug compared to MMF in patients with moderate to severe active PV. Patients received either MabThera/Rituxan plus MMF placebo or MabThera/Rituxan placebo plus MMF for 52 weeks in combination with 60 or 80 mg oral prednisone. Patients received 100 mg via IV infusion of MabThera/Rituxan on day 1 and 15, with another dose at 168 and 182 days. MMF was given at 2 grams orally daily beginning on Day 1 received amounts equivalent to 2 grams per day by Week 2.

The primary endpoint at Week 52 was the percentage of patients who hit sustained complete remission without experiencing treatment failure. Sustained complete remission was defined as healing of lesions with no new active lesions while on 0 mg/day prednisone or equivalent and then holding that response for at least 16 consecutive weeks.

MabThera (Rituxan in the United States) is prescribed for four autoimmune diseases: moderate to severe pemphigus vulgaris; in combination with glucocorticoids for granulomatosis with polyangiitis (Wegener’s granulomatosis, GPA) and microscopic polyangiitis (MPA) in adults; for the same indication in pediatric patients two years of age and older; in combination with methotrexate for adults with severe active rheumatoid arthritis (RA) who don’t respond to or are intolerant to other disease-modifying anti-rheumatic drugs (DMARD).

“The approval of MabThera/Rituxan for the treatment of pemphigus vulgaris was the first major advancement in the treatment of this rare, serious disease in more than 60 years,” said Levi Garray, Roche’s chief medical officer and head of Global Product Development. “The PEMPHIX study showed that 40% of people in the study could achieve complete remission from painful blistering without the need for corticosteroids for 16 weeks or more and that Mabthera/Rituxan may be a superior treatment option to mycophenolate mofetil.”

In 2018, Rituxan brought in $4.29 billion in the U.S. alone. The company expected biosimilar competition in 2018, but that didn’t happen. The FDA approved Pfizer’s Ruxience (rituximab-pvvr), a biosimilar to Rituxan, in July 2019. It wasn’t approved, however, for RA. As of July 24, there was no launch date announced. Pfizer settled with Roche over a key patent for the brand-name rituximab.

Celltrion and Teva’s Truxima is also a biosimilar to rituximab, but it was only approved for the cancer indications because of U.S. patent challenges. It is not on the market in the U.S. yet.