FDA Grants Priority Review to Rituxan Plus Glucocorticoids for Children with GPA and MPA

The U.S. Food and Drug Administration (FDA) has granted Priority Review to Rituxan (rituximab) in combination with glucocorticoids for the treatment of children, 2 or older, with granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA).

If Genentech‘s Biologics License Application (sBLA) for Rituxan is approved, this will be the first indication of the treatment for children.

GPA and MPA are two subtypes of ANCA-associated vasculitis (AAV), an autoimmune inflammatory disorder characterized by inflammation and damage to small- and medium-sized blood vessels.

Rituxan is an antibody that binds to the CD20 protein found at the surface of B-cells, a type of immune cell that makes antibodies and plays a role in autoimmune diseases. The binding of Rituxan to CD20 results in a reduction in B-cell levels, through a variety of mechanisms.

The treatment is approved in the U.S. for multiple cancer and autoimmune indications, including for the treatment of adults with GPA or MPA, in combination with glucocorticoids.

Aiming to determine if this indication could be extended to children with the conditions, researchers at Roche conducted an open-label, single-arm, Phase 2a clinical trial (NCT01750697), called PePRS, which supported the recent sBLA.

PePRS tested the safety, pharmacokinetics (processing inside the body), and exploratory efficacy parameters of Rituxan in children and adolescents, from 2 and 17 years old, with severe GPA and MPA.

The study enrolled 25 patients — 19 with GPA, six with MPA — whose disease was newly diagnosed or had returned after prior treatment (relapsed). Most were girls (80%), with a median age of 14 years (range 6–17 years).

Participants received blood infusions of 375 mg/m² Rituximab in four weekly doses, and a tapering course of oral glucocorticoids. After a remission induction phase that lasted six months, they received standard of care management for disease control, which included additional Rituxan infusions if required. They were followed for up to 18 months.

The study’s findings, presented at last year’s American College of Rheumatology Annual Meeting, showed that Rituxan was well-tolerated, with an overall safety profile similar to that of adults. No new safety issues were observed.

Side effects included infusion-related reactions, headaches, nausea, upper respiratory tract infection, abdominal pain, constipation, joint and back pain, cough, and nose bleeds. Seven patients experienced a total of 10 serious adverse events, including one infusion-related reaction.

An exploratory efficacy analysis also indicated that remission was achieved by 56% of the patients within the remission induction period. By month 18, all patients were in remission. The median duration of remission was 56 weeks.

Remission was defined as a pediatric vasculitis activity score (PVAS; a measure of disease activity in children) of zero and an oral glucocorticoid dose of 0.2 mg/kg per day or less.

“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 of Genentech, said in a press release. “We will continue to work closely with the FDA to bring Rituxan to children with these two serious and potentially life-threatening diseases.”