FDA Grants Priority Review to Rituximab for Pemphigus Vulgaris

Sandra Horning, MD

The US Food and Drug Administration (FDA) has accepted a Supplemental Biologics License Application (sBLA) and granted Priority Review designation to rituximab (Rituxan, Genentech), a treatment for the rare autoimmune condition pemphigus vulgaris (PV).

The drug had been previously given Breakthrough Therapy and Orphan Drug designations, as the treatment options for patients with PV are very limited to only a few immunosuppressant therapies, such as azathloprine, mycophenolate, cyclophosphamide, and cyclosporine.

“We are committed to developing medicines for rare diseases with limited treatment options, such as pemphigus vulgaris,” Sandra Horning, MD, the chief medical officer and head of Global Product Development at Genentech said in a statement. “We look forward to continued work with the FDA to hopefully provide patients with a new treatment for this serious and potentially life-threatening disease.”

PV reportedly affects about 30,000 to 40,000 Americans each year, according to the International Pemphigus & Pemphigoid Foundation.

The FDA reviewed the submission based on data from a randomized clinical trial done in 25 hospital departments in France that evaluated 1000 mg rituximab on day 0 and day 14— followed by a 500-mg dose at months 12 and 18—in conjunction with a narrowing dose of the oral corticosteroid therapy prednisone starting at 0.5 mg or 1.0 mg (n = 90), compared with a standard dose of prednisone as monotherapy 9n = 91). The trial included 181 patients in total.

The trial found that 89% (n = 41) of those assigned to rituximab plus short-term prednisone were completely in remission and off therapy by month 24. In comparison, only 34% (n = 15) of those on prednisone alone achieved remission (absolute difference, 55 percentage points; 95% CI, 38.4-71.7; P <.0001).

Additionally, more severe adverse events (sAEs) of grades 3 to 4 were reported in the prednisone-only group (53 events in 29 patients; mean, 1.20 [SD, 1.25]) than in the rituximab plus prednisone group (27 events in 16 patients; mean, 0·59 [1.15]; P = .0021). The most common sAEs in the 2 groups were diabetes and endocrine disorder, which occurred in 11 patients in the prednisone group (21%) compared with 6 in the rituximab group (22%); myopathy, which occurred in 10 (19%) and 3 (11%) patients, respectively; and bone disorders, with occurred in 5 (9%) and 5 (19%) patients, respectively.

The therapy can, however, cause sAEs, such as infusion reactions; severe skin and mouth reactions including painful sores or ulcers, blisters, peeling skin, rash, or pustules; hepatitis B virus (HBV) reactivation; and progressive multifocal leukoencephalopathy (PML); tumor lysis syndrome (TLS); serious infections; heart, kidney, and bowel problems; and low blood cell counts.

Currently, another phase 3 trial is underway to evaluate rituximab and a tapering dose of corticosteroid compared mycophenolate (CellCept, Genentech) to according to Genentech.