FDA Approves Genentech’s Rituxan (rituximab) in Children With Two Rare Blood Vessel Disorders

“Rituxan is now approved as the first and only medicine for pediatric patients living with GPA and MPA, two potentially life-threatening blood vessel disorders which are rare in children,” said Sandra Horning, M.D., chief medical officer and head of Global Product Development. “Today’s approval is a result of our ongoing commitment to working with the FDA to develop medicines for pediatric patients with rare diseases where there is a serious unmet need.”

The approval is based on data from the PePRS study, a Phase IIa, global, open-label, multi-center, single-arm study investigating the safety, pharmacokinetics, exploratory efficacy and pharmacodynamic outcomes of intravenous Rituxan in 25 patients with active GPA or MPA between 6 and 17 years of age. Treatment with four weekly infusions of Rituxan or non-U.S.-licensed rituximab in combination with a tapering course of oral glucocorticoids was assessed in newly diagnosed or relapsing active GPA or MPA pediatric patients. Of the 25 patients in the study, 19 had GPA and 6 had MPA at baseline. Efficacy was an exploratory endpoint and primarily assessed using the Pediatric Vasculitis Activity Score (PVAS). Efficacy assessment showed that 56% of patients achieved PVAS remission by month 6, 92% by month 12, and 100% of patients achieved remission by month 18. The safety profile of Rituxan in patients with pediatric GPA and MPA was consistent in type, nature and severity with the known safety profile of Rituxan in adult patients with GPA, MPA, rheumatoid arthritis and pemphigus vulgaris

The FDA previously granted Priority Review to Rituxan for the treatment of GPA and MPA in pediatric patients. In 2011, Rituxan became the first and only therapy approved by the FDA for the treatment of adults with these two rare forms of vasculitis. Rituxan is currently indicated for the treatment of four autoimmune conditions and since 2006 more than 900,000 people have been treated with Rituxan for autoimmune conditions worldwide. Rituxan is not indicated in children less than 2 years of age with GPA or MPA, or in children with conditions outside of GPA and MPA.

About Granulomatosis with Polyangiitis and Microscopic Polyangiitis

Granulomatosis with Polyangiitis (GPA) (formerly known as Wegener’s Granulomatosis) and Microscopic Polyangiitis (MPA) are two types of ANCA-associated vasculitis (AAV). AAV is a form of vasculitis, or blood vessel inflammation, that primarily affects small blood vessels. In general, GPA and MPA both affect the small blood vessels of the kidneys, lungs, sinuses, and a variety of other organs, but the diseases may affect each person differently. Both GPA and MPA are considered rare diseases, with an estimated prevalence in the United States of up to 3 cases per 100,000 people. Cases of pediatric onset GPA and MPA are even more rare and are associated with severe, potentially life-threatening symptoms.

What autoimmune diseases does Rituxan treat?

Rheumatoid arthritis (RA): with another prescription medicine called methotrexate, to reduce the signs and symptoms of moderate to severe active RA in adults, after treatment with at least one other medicine called a tumor necrosis factor (TNF) antagonist has been used and did not work well enough.

Granulomatosis with Polyangiitis (GPA) (Wegener’s Granulomatosis) and Microscopic Polyangiitis (MPA): with glucocorticoids, to treat adults and pediatric patients 2 years of age and older with GPA and MPA.

Pemphigus vulgaris (PV): to treat adults with moderate to severe PV.

Rituxan is not indicated in children less than 2 years of age with GPA or MPA, or in children with conditions outside of GPA and MPA.

Important Side Effect Information

What is the most important information patients should know about Rituxan?

Rituxan can cause serious side effects that can lead to death, including:

• Infusion-Related Reactions: Infusion-related reactions are very common side effects of Rituxan treatment. Serious infusion-related reactions can happen during your infusion or within 24 hours after your infusion of Rituxan. Your healthcare provider should give you medicines before your infusion of Rituxan to decrease your chance of having a severe infusion-related reaction
• Severe Skin and Mouth Reactions: Tell your healthcare provider or get medical help right away if you get any of these symptoms at any time during your treatment with Rituxan: painful sores or ulcers on your skin, lips, or in your mouth; blisters; peeling skin; rash; or pustules
• Hepatitis B Virus (HBV) Reactivation: If you have had hepatitis B or are a carrier of hepatitis B virus, receiving Rituxan could cause the virus to become an active infection again. Hepatitis B reactivation may cause serious liver problems, including liver failure and death. You should not receive Rituxan if you have active hepatitis B liver disease. Your healthcare provider will monitor you for hepatitis B infection during and for several months after you stop receiving Rituxan
• Progressive Multifocal Leukoencephalopathy (PML):PML is a rare, serious brain infection caused by a virus that can happen in people who receive Rituxan. People with weakened immune systems can get PML. PML can result in death or severe disability. There is no known treatment, prevention, or cure for PML

Before receiving Rituxan, patients should tell their healthcare provider if they:

• have had a severe reaction to Rituxan or a rituximab product
• currently have or have a history of other medical conditions, especially heart disease
• have had a severe infection, currently have an infection, or have a weakened immune system
• have had a recent vaccination or are scheduled to receive vaccinations
• are pregnant or planning to become pregnant. Females who are able to become pregnant should use effective birth control (contraception) during treatment with Rituxan and for 12 months after the last dose of Rituxan
• are breastfeeding or plan to breastfeed. Patients should not breastfeed during treatment and for at least 6 months after the last dose of Rituxan
• are taking any medications, including prescription and over-the-counter medicines, vitamins, and herbal supplements

What are the possible side effects of Rituxan?

Rituxan can cause serious and life‐threatening side effects, including:

• Tumor Lysis Syndrome (TLS): TLS is caused by the fast breakdown of cancer cells. TLS can cause you to have kidney failure and the need for dialysis treatment or may cause an abnormal heart rhythm. Tell your healthcare provider right away if you have any of the following signs or symptoms of TLS: nausea, vomiting, diarrhea, or lack of energy
• Serious Infections: Serious infections can happen during and after treatment with Rituxan and can lead to death. Rituxan can increase your risk of getting infections and can lower the ability of your immune system to fight infections. People with serious infections should not receive Rituxan
• Heart Problems: Rituxan may cause chest pain, irregular heartbeats, and heart attack. Your healthcare provider may monitor your heart during and after treatment with Rituxan if you have symptoms of heart problems or have a history of heart problems
• Kidney Problems: especially if you are receiving Rituxan for non-Hodgkin’s lymphoma (NHL). Your healthcare provider should do blood tests to check how well your kidneys are working
• Stomach and Serious Bowel Problems That Can Sometimes Lead to Death: Tell your healthcare provider right away if you have any stomach-area pain during treatment with Rituxan

What are the most common side effects during treatment with Rituxan?

The most common side effects of Rituxan include:

• infusion-related reactions
• infections (may include fever, chills)
• body aches
• tiredness
• nausea

In adult patients with GPA or MPA, the most common side effects of Rituxan also include:

• low white and red blood cells
• swelling
• diarrhea
• muscle spasms

Other side effects include:

• aching joints during or within hours of receiving an infusion
• more frequent upper respiratory tract infections

These are not all of the possible side effects with Rituxan. For more information, ask a doctor or pharmacist.

Contact a doctor for medical advice about side effects. Report side effects to the FDA at (800) FDA‐1088 or http://www.fda.gov/medwatch. Patients may also report side effects to Genentech at (888) 835‐2555.

Please see the Rituxan Prescribing Information and Medication Guide including Most Serious Side Effects for additional Important Side Effect Information at http://www.rituxan.com.

Genentech and Biogen collaborate on Rituxan in the United States, and Roche markets MabThera in the rest of the world, except Japan, where Rituxan is co-marketed by Chugai and Zenyaku Kogyo Co. Ltd.

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