FDA Approves First Treatment for Children With Rare Diseases That Cause Inflammation of Small Blood Vessels

September 28, 2019

The US Food and Drug Administration (FDA) has approved rituximab (Rituxan) injection to treat granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) in children aged ≥2 years in combination with glucocorticoids.

This is the first approved treatment for children with these rare vasculitis diseases, in which a patient’s small blood vessels become inflamed, reducing the amount of blood that can flow through them. This can cause serious problems and damage to organs, most notably the lungs and kidneys. It also can impact the sinuses and skin.

“The rituximab application for paediatric 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,” said Nikolay Nikolov, MD, FDA Center for Drug Evaluation and Research, Rockville, Maryland. “Rituximab provides a treatment option that has not existed until now for children who suffer from these diseases.”

The safety profile in paediatric 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 paediatric clinical trial consisted of 25 patients aged 6 to 17 years with active GPA and MPA who were treated with rituximab or non-US-licensed rituximab in an international multicentre, 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 where patients were treated only with rituximab or non-US-licensed rituximab and glucocorticoids, patients who had not achieved remission -- or who had progressive disease or an uncontrolled flare-up -- 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 pharmacokinetic and safety information supported the use of rituximab in patients aged 2 to 5 years with GPA/MPA.

The most common side effects in the paediatric study were infections, infusion-related reactions, and nausea. Hypogammaglobulinemia has also been observed in paediatric patients with GPA and MPA treated with the study products.

The most common side effects of rituximab are infections, infusion-related reactions, lymphopenia, and anaemia.

Healthcare professionals are advised to monitor patients for tumour lysis syndrome, cardiac adverse reactions, renal toxicity, and bowel obstruction and perforation.

The doctor and patient information for rituximab contains a Boxed Warning to draw attention to increased risks of the following: fatal infusion reactions; potentially fatal severe skin and mouth reactions; hepatitis B virus reactivation that may cause serious liver problems, including liver failure and death; and progressive multifocal leukoencephalopathy.

This product must be dispensed with a patient Medication Guide that provides important information about the drug’s uses and risks.

Rituximab was approved to treat adult patients with GPA and MPA in 2011. It is also approved to treat 4 additional diseases, first gaining approval to treat non-Hodgkin’s lymphoma in 1997.

Rituximab received Priority Review designation, under which the FDA’s goal is to take action on an application within 6 months where the agency determines that the drug, if approved, would significantly improve the safety or effectiveness of treating, diagnosing, or preventing a serious condition. Rituxan also received Orphan Drug designation, which provides incentives to assist and encourage the development of drugs for rare diseases.

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 1-800-FDA-1088.

SOURCE: The US Food and Drug Administration