FDA Grants Priority Review to Rituximab for Children with 2 Rare Forms of Vasculitis
Genentech is seeking approval for rituximab (Rituxan) with glucocorticoids for pediatric patients with granulomatosis with polyangiitis and microscopic polyangiitis.
Officials with the FDA granted Priority Review to Genentech’s supplemental Biologics License Application (sBLA) for rituximab (Rituxan) in combination with glucocorticoids (GCCs) for the treatment of 2 rare forms of vasculitis in pediatric patients, according to a press release.
If approved, rituximab plus GCCs would be indicated for the treatment of granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) in children 2 years of age and older. Currently, rituximab plus GCCs is the only FDA-approved therapy for the treatment of adults with these 2 conditions and approval of the sBLA would represent the first pediatric indication for rituximab.
GPA and MPA are rare, potentially life-threatening diseases that affect small- and medium-sized blood vessels, primarily in the kidneys, lungs, sinuses, and a variety of other organs. Cases of pediatric onset of these conditions are even more rare and can result in severe, life-threatening symptoms, according to Genentech.
The sBLA submission was based on data from the phase 2a PePRS study evaluating the safety, pharmacodynamics/pharmacokinetics, and exploratory efficacy of intravenous rituximab. The trial included 25 patients with severe GPA or MPA between 6 and 17 years old. In the study, pediatric patients with newly-diagnosed or relapsing active GPA or MPA were treated with 4 weekly infusions of rituximab in combination with a tapering course of oral GCCs. The results demonstrated no new safety signals with rituximab treatment.
All 25 patients completed the first 4 rituximab infusions and the 6-month induction phase and 24 patients completed ≥18 months of follow up. Infusion-related reactions were the most common adverse effect (AE), occurring in 32% of patients with the first infusion and were less frequent thereafter, according to the study. Sixty-eight percent of patients acquired infections and 10 serious AEs occurred in 7 patients during the 6-month remission induction phase. Over the course of the study, 27 serious AEs were reported in 12 patients but no deaths were reported.
According to the exploratory efficacy assessment, 56% of patients achieved remission by month 6 and 100% achieved remission by month 18. Overall, the median duration of remission during the study was 56 weeks.
Rituximab is currently indicated for 4 autoimmune diseases: GPA, MPA, pemphigus vulgaris, and rheumatoid arthritis.
“We are committed to delivering new treatment options for rare diseases, such as pediatric GPA and MPA, for which there are currently no approved medicines,” Sandra Horning, MD, chief medical officer and head of Global Product Development, Genentech, said in a statement. “We will continue to work closely with the FDA to bring Rituxan to children with these 2 serious and potentially life-threatening diseases.”
FDA Grants Priority Review to Genentech’s Rituxan (Rituximab) in Children With Two Rare Blood Vessel Disorders [news release]. Genentech. https://www.gene.com/media/press-releases/14797/2019-06-11/fda-grants-priority-review-to-genentechs. Accessed June 12, 2019.
Brogan P, Cleary G, Hersh AO, et al. Pediatric open-label clinical study of rituximab for the treatment of granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 10).