Wednesday, Jun 12, 2019

Phase III PEMPHIX Study Showed That Genentech’s Rituxan (Rituximab) is Superior to Standard of Care in Achieving Sustained Remission in Patients with Pemphigus Vulgaris

• Rituxan met the primary and secondary endpoints in the Phase III PEMPHIX study
• Rituxan was the first and only biologic therapy approved by the FDA in June 2018 for the treatment of pemphigus vulgaris based on results from the Ritux 3 clinical trial
• Results will be submitted to health authorities around the world, including the U.S. Food and Drug Administration (FDA)

South San Francisco, CA -- June 12, 2019 --

Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), today announced positive top line results from the Roche-sponsored Phase III PEMPHIX study evaluating the efficacy and safety of Rituxan^® (rituximab) compared to mycophenolate mofetil (MMF) in adults with moderate to severe pemphigus vulgaris (PV). The study met the primary endpoint, and demonstrated that Rituxan is superior to MMF in achieving sustained complete remission.

“The PEMPHIX study provides additional clinical evidence for the use of Rituxan for the treatment of pemphigus vulgaris,” said Sandra Horning, M.D., chief medical officer and head of Global Product Development. “These data also demonstrated that Rituxan may provide complete remission rates and successful tapering of corticosteroid therapy that is superior to MMF in adults with pemphigus vulgaris.”

The primary endpoint was the percentage of participants who achieved sustained complete remission off corticosteroid therapy (no disease activity, as evaluated by Pemphigus Disease Area Index, without the use of steroids for 16 consecutive weeks or more) at Week 52. Rituxan also met the secondary endpoints, including cumulative corticosteroid dose, number of flares, time to sustained remission and time to disease flare. Adverse events were generally consistent with those seen in previous Rituxan clinical studies for other autoimmune indications.

PV is a rare, serious and potentially life-threatening condition characterized by progressive painful blistering of the skin and mucous membranes.¹ MMF is an unapproved treatment for PV that is accepted as standard of care. In June 2018, Rituxan became the first biologic therapy approved by the FDA for PV and the first major advancement in the treatment of the disease in more than 60 years. This approval was based on the Ritux 3 clinical trial.² This PEMPHIX trial provided additional clinical evidence on the effectiveness of Rituxan for PV. Complete data from the PEMPHIX study will be presented at an upcoming medical congress.

About the PEMPHIX study

PEMPHIX is a Phase III, randomized, double-blind, double-dummy, active-comparator, parallel-arm multicenter study (NCT02383589) designed to evaluate the efficacy and safety of Rituxan compared with mycophenolate mofetil (MMF) in patients with moderate to severe active pemphigus vulgaris requiring 60-120 mg/day oral prednisone (or equivalent). Participants were randomly assigned to receive Rituxan plus MMF placebo or Rituxan placebo plus MMF. Rituxan was administered at a dose of 1000 mg via IV infusion on day 1 and 15, with a repeat administration on days 168 and 182. MMF was administered at a dose of 2 grams orally daily from day 1 to week 52. The primary endpoint is the percentage of participants who achieved sustained complete remission, evaluated by the Pemphigus Disease Area Index (PDAI) Activity Score, for at least 16 consecutive weeks at Week 52. Secondary endpoints include cumulative oral corticosteroid dose, number of disease flares, time to sustained complete remission, time to disease flare and health-related quality of life, as measured by the Dermatology Life Quality Index.

About Pemphigus Vulgaris

Pemphigus vulgaris is an autoimmune blistering disease affecting the skin and mucous membranes.¹ This rare, potentially life-threatening condition accounts for up to 80 percent of cases of pemphigus, a group of autoimmune disorders which affect 30,000 to 40,000 people in the United States. ³

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-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 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. Medscape. Pemphigus Vulgaris. Available at: http://emedicine.medscape.com/article/1064187-overview. [Last accessed: February 14, 2019]

2. Joly P, et al. First-Line Rituximab Combined with Short-Term Prednisone Versus Prednisone Alone for the Treatment of Pemphigus (Ritux 3): A Prospective, Multicentre, Parallel-Group, Open-Label Randomised Trial. The Lancet. March 22, 2017

3. International Pemphigus & Pemphigoid Foundation. Pemphigus. Available at: http://www.pemphigus.org/research/clinically-speaking/pemphigus/. [Last accessed: February 14, 2019]

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