Rituxan Gets Approval for 2 Pediatric Vasculitis Conditions

The FDA has approved another indication for reference rituximab (Rituxan), this time for children with rare vasculitis diseases.

The approval, for granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) in children 2 years of age and older in combination with glucocorticoids (steroid hormones), is the first approved treatment for these conditions.

In these disease, small blood vessels become inflamed, reducing the amount of blood that can flow through them and risking organ damage, particularly to the lungs and the kidneys. The conditions can also can impact the sinuses and skin.

Rituxan, sold by Genentech, was approved to treat adult patients with GPA and MPA in 2011. It is also approved to treat 9 additional diseases, including 4 autoimmune conditions; its first approval, for non-Hodgkin's lymphoma, was in 1997.

“The Rituxan application for pediatric GPA and MPA was approved under a priority review, and with orphan designation, to fulfil an unmet medical need for these rare and serious diseases. Rituxan provides a treatment option that has not existed until now for children who suffer from these diseases,” said Nikolay Nikolov, MD, associate director for rheumatology of the Division of Pulmonary, Allergy and Rheumatology Products in the FDA’s Center for Drug Evaluation and Research.

The safety profile in pediatric patients with GPA, formerly known as Wegener's granulomatosis, and MPA was consistent in type, nature and severity with the known safety profile of rituximab in adult patients with autoimmune diseases, including GPA and MPA.

The pediatric clinical trial consisted of 25 patients ages 6 to 17 years with active GPA and MPA who were treated with Rituxan or non-US-licensed rituximab in an international multicenter, open-label, single-arm, uncontrolled study. All patients were given methylprednisolone prior to starting treatment.

During the clinical trial, after a 6-month remission induction phase in which patients were treated only with US Rituxan or non-US-licensed rituximab and glucocorticoids, patients who had not achieved remission—or who had progressive disease or an uncontrolled flare-up (when disease symptoms suddenly worsen) —could receive additional treatment, including other therapies, at the discretion of the investigator.

In total, 14 of the patients were in remission at the 6-month mark. After 18 months, all 25 patients were in remission. Additional exposure and safety information supported the use of rituximab in patients 2 years to 5 years of age with GPA or MPA. Infections, infusion-related reactions, and nausea were the most common side effects; hypogammaglobulinemia (reduced serum immunoglobulin levels) has also been observed in pediatric GPA and MPA patients.

There is an approved biosimilar for this indication, but only for adults. In July, the FDA approved Pfizer’s rituximab biosimilar, Ruxience (rituximab-pvvr) for non-Hodgkin lymphoma, chronic lymphocytic leukemia, and granulomatosis with polyangiitis and microscopic polyangiitis in adults.

As the FDA noted, Rituxan received Priority Review Designation as well as Orphan Drug Designation for the additional indications, a practice that has started to come under scrutiny from some quarters.