FDA Approves Label Update for Genentech’s Rituxan (Rituximab) in Two Rare Forms of Vasculitis

Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), announced today that the U.S. Food and Drug Administration (FDA) has approved an update to the Rituxan® (rituximab) label to include information on follow up treatment of adult patients with Granulomatosis with Polyangiitis (GPA) and Microscopic Polyangiitis (MPA) who have achieved disease control with induction treatment. The label update was based on data from a Roche-supported study by the French Vasculitis Study Group showing that treatment with the rituximab regimen* resulted in fewer major relapses by month 28 compared to treatment with azathioprine. The observed safety profile was consistent with that previously observed in this patient population. Rituxan, in combination with glucocorticoids (GCC), was approved by the FDA in 2011 for adult patients with GPA and MPA.

“Options for continued treatment in GPA and MPA, chronic autoimmune diseases in which patients experience periods of flares, are currently limited,” said Sandra Horning, M.D., chief medical officer and head of Global Product Development. “As part of our commitment to support people living with rare diseases, we are pleased to provide updated prescribing information for Rituxan to help physicians make more informed decisions about therapeutic options for patients who have achieved disease control with induction treatment.”

GPA and MPA are two types of ANCA-associated vasculitis (AAV), a form of vasculitis, or inflammation of the blood vessels, that largely affects the small blood vessels of the kidneys, lungs and a variety of other organs.1 Rituxan, in combination with glucocorticoids (GCC), was approved by the FDA in 2011 for adult patients with GPA and MPA, with the precaution that limited data were available on the safety and efficacy of subsequent courses of Rituxan in patients with GPA and MPA, and that the safety and efficacy of retreatment with Rituxan had not been established. As part of this label update, the precaution has been removed from the Rituxan prescribing information.

The U.S. label update is based on data from the MAINRITSAN trial, a Roche-supported, randomized, controlled clinical trial, conducted by the French Vasculitis Study Group, that used Roche-manufactured, European Union (EU)-approved rituximab as the clinical trial material. The study evaluated the efficacy and safety of the rituximab regimen compared to azathioprine as follow up treatment in 115 patients (86 with GPA, 24 with MPA, and 5 with renal-limited AAV), who had achieved disease control after induction of remission with GCC and cyclophosphamide.2 The primary endpoint was the occurrence of major relapse† through month 28. By month 28, major relapse occurred in 3 patients (5 percent) on the rituximab regimen* and 17 patients (29 percent) in the azathioprine group.

*Rituximab regimen = Roche-manufactured, European Union (EU)-approved rituximab + glucocorticoids

†Major relapse in the trial was defined by the reappearance of clinical and/or laboratory signs of vasculitis activity that could lead to organ failure or damage, or could be life threatening

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).1 AAV is a form of vasculitis, or blood vessel inflammation, that primarily affects small blood vessels.1 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.3,4 Historically, untreated AAV has a poor prognosis: more than 80 percent of untreated patients die within one year of diagnosis, most frequently from renal or respiratory failure.5 Both GPA and MPA are considered rare diseases, with an estimated prevalence in the United States of up to three cases per 100,000 people.3,4

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 GPA and MPA.

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

It is not known if Rituxan is safe or effective in children.

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 Reactions: Infusion reactions are the most common side effect of Rituxan treatment. Serious infusion reactions can happen during an infusion or within 24 hours after an infusion
• Severe Skin and Mouth Reactions: Painful sores or ulcers on skin, lips, or in the mouth; blisters, peeling skin, rash, or pustules
• Hepatitis B Virus (HBV) Reactivation: If a patient has had hepatitis B or is a carrier of hepatitis B virus, receiving Rituxan could cause the virus to become an active infection again
• Progressive Multifocal Leukoencephalopathy (PML): A rare, serious brain infection caused by the JC virus

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

• have had a severe infusion reaction to Rituxan in the past
• 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 kidney failure and the need for dialysis treatment or may cause an abnormal heart rhythm
• Serious Infections: Serious infections can happen during and after treatment with Rituxan and can lead to death
• Heart Problems: Rituxan may cause chest pain and irregular heartbeats, which may need treatment, or a patient’s doctor may decide to stop treatment with Rituxan
• Kidney Problems: Especially if a patient is receiving Rituxan for non-Hodgkin’s lymphoma (NHL). Doctors should do blood tests to check how well a patient’s kidneys are working
• Stomach and Serious Bowel Problems That Can Sometimes Lead to Death: Patients should inform their doctor right away if they have any stomach area pain during treatment with Rituxan
• Low Blood Cell Counts: A doctor may do blood tests during treatment with Rituxan to check a patient’s blood cell counts

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

• Infusion reactions
• Infections (may include fever, chills)
• Body aches
• Tiredness
• Nausea

In 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.

About Genentech

Founded more than 40 years ago, Genentech is a leading biotechnology company that discovers, develops, manufactures and commercializes medicines to treat patients with serious and life-threatening medical conditions. The company, a member of the Roche Group, has headquarters in South San Francisco, California. For additional information about the company, please visit http://www.gene.com.

References

1. Genetic and Rare Diseases Information Center (GARD), National Center for Advancing Translational Sciences (NCATS), National Institutes of Health (NIH). ANCA-associated vasculitis. Available at: https://rarediseases.info.nih.gov/diseases/13011/anca-associated-vasculitis [Last accessed: August 1, 2018]

2. Guillevin L, et al. Rituximab versus azathioprine for maintenance in ANCA-associated vasculitis. N Engl J Med. 2014;371(19):1771–80.

3. Medscape. Granulomatosis with Polyangiitis (Wegener Granulomatosis). Available at: https://emedicine.medscape.com/article/332622-overview#showall. [Last accessed: August 1, 2018]

4. Medscape. Microscopic Polyangiitis. Available at: https://emedicine.medscape.com/article/334024-overview#showall. [Last accessed: August 1, 2018]

5. Booth AD et al. Outcome of ANCA-associated renal vasculitis: a 5-year retrospective study. Am J Kidney Dis. 2003; 41 776

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