FDA Approves Genentech’s Actemra (Tocilizumab) For The Treatment Of CAR T Cell-Induced Cytokine Release Syndrome

• Actemra is the first FDA-approved treatment for severe or life-threatening cytokine release syndrome induced by CAR T cell therapy
• CAR T cell therapy is an immunotherapy designed for the treatment of certain cancers
• This is the seventh FDA approval for Actemra since its U.S. launch in 2010

SOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)--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 Actemra^® (tocilizumab) intravenous injection for the treatment of chimeric antigen receptor (CAR) T cell-induced severe or life-threatening cytokine release syndrome (CRS) in patients two years of age and older. CRS, which is caused by an overactive immune response, has been identified as a potentially severe and life-threatening side effect of CAR T cell therapy for certain cancers.¹

“Until today, there has never been an FDA-approved treatment to manage severe cytokine release syndrome associated with CAR T cell therapy, which is marked by a rapid onset and can cause life-threatening complications”

“Until today, there has never been an FDA-approved treatment to manage severe cytokine release syndrome associated with CAR T cell therapy, which is marked by a rapid onset and can cause life-threatening complications,” said Sandra Horning, M.D., chief medical officer and head of Global Product Development. “Today’s approval of Actemra for cytokine release syndrome provides physicians with an important tool to help manage this potentially life-threatening side effect.”

The approval is based on a retrospective analysis of pooled outcome data from clinical trials of CAR T cell therapies for blood cancers, which assessed the efficacy of Actemra in the treatment of CRS.² The study population included 45 pediatric and adult patients treated with Actemra, with or without additional high-dose corticosteroids, for severe or life-threatening CRS. Thirty-one patients (69%; 95% CI: 53%–82%) achieved a response, defined as resolution of CRS within 14 days of the first dose of Actemra, no more than two doses of Actemra were needed, and no drugs other than Actemra and corticosteroids were used for treatment. No adverse reactions related to Actemra were reported.² A second study confirmed resolution of CRS within 14 days using an independent cohort that included 15 patients with CAR T cell-induced CRS.

The FDA granted Priority Review and Orphan Drug Designation to Actemra for the treatment of CAR T cell-induced CRS based on the rare, severe and life-threatening nature of CRS and available data on the safety and efficacy of Actemra. Priority Review Designation is granted to medicines that the FDA has determined to have the potential to provide significant improvements in the safety and effectiveness of the treatment of a serious condition. Orphan Drug Designation may be granted to medicines intended for the treatment of conditions that affect fewer than 200,000 people in the United States.

About CAR T Cell Therapy-Induced Cytokine Release Syndrome

CAR T cell therapies are designed for the treatment of certain cancers by modifying an individual patient’s own cells to specifically target the cancer cells. CRS, which is caused by an overactive immune response, has been identified as a potentially severe and life-threatening side effect of CAR T cell therapies. Most people with CRS experience mild or moderate flu-like symptoms which are easily managed. However, some patients experience more severe symptoms that may lead to potentially life-threatening complications such as cardiac dysfunction, acute respiratory distress syndrome or multi-organ failure.¹

About Actemra

Actemra is the first humanized interleukin-6 (IL-6) receptor antagonist approved for the treatment of adult patients with moderately to severely active rheumatoid arthritis (RA) who have used one or more disease-modifying antirheumatic drugs (DMARDs), such as methotrexate (MTX), that did not provide enough relief. The extensive Actemra RA IV clinical development program included five Phase III clinical studies and enrolled more than 4,000 people with RA in 41 countries. The Actemra RA subcutaneous clinical development program included two Phase III clinical studies and enrolled more than 1,800 people with RA in 33 countries. Actemra subcutaneous injection is also approved for the treatment of adult patients with giant cell arteritis (GCA). In addition, Actemra is also used as the IV formulation for patients two years of age and older with active polyarticular juvenile idiopathic arthritis (PJIA), systemic juvenile idiopathic arthritis (SJIA) or CAR T cell-induced cytokine release syndrome (CRS). Actemra is not approved for subcutaneous use in people with PJIA, SJIA or CRS. It is not known if Actemra is safe and effective in children with PJIA, SJIA or CRS under two years of age or in children with conditions other than PJIA, SJIA or CRS.

Actemra is intended for use under the guidance of a healthcare practitioner.

Important Safety Information

Actemra can cause serious side effects. Actemra changes the way a patient’s immune system works. This can make a patient more likely to get infections or make any current infection worse. Some people taking Actemra have died from these infections.

Actemra can cause other serious side effects. These include:

• Stomach tears
• Changes in blood test results, including low neutrophil (white blood cells) and platelet (platelets help the blood to clot) counts, and increases in certain liver function test levels and blood cholesterol levels
• An increased risk of certain cancers by changing the way a patient’s immune system works
• Hepatitis B infection
• Serious allergic reactions, including death. These may happen with Actemra infusions or injections, even if they did not occur with an earlier infusion or injection.
• Nervous system problems

Patients should not receive Actemra if they are allergic to Actemra or if they have had a bad reaction to Actemra previously.

Common side effects in patients treated with Actemra:

Patients should tell their doctor if they have these or any other side effect that bothers them or does not go away:

• Upper respiratory tract infections (like common cold and sinus infections)
• Headache
• Increased blood pressure (also called hypertension)
• Injection site reactions

Actemra & pregnancy:

Patients should tell their doctor if they are planning to become pregnant, are pregnant, plan to breastfeed, or are breastfeeding. The patient and their doctor should decide if the patient will take Actemra or breastfeed. Patients should not do both. If a patient is pregnant and taking Actemra, they should join the pregnancy registry. To learn more, patients should call 1-877-311-8972 or talk to their doctor to register.

Patients should tell their doctor right away if they are experiencing any side effects. Report side effects to the FDA at 1-800-FDA-1088 or http://www.FDA.gov/medwatch. Report side effects to Genentech at 1-888-835-2555.

Please visit http://www.actemra.com for the full Prescribing Information, including Boxed Warning and Medication Guide, for additional Important Safety Information or call 1-800-ACTEMRA (228-3672).

Actemra is part of a co-development agreement with Chugai Pharmaceutical Co. and has been approved in Japan since June 2005. Actemra is approved in the European Union, where it is known as RoActemra, and several other countries, including China, India, Brazil, Switzerland and Australia.

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 or 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. Lee DW, et al. Current concepts in the diagnosis and management of cytokine release syndrome. Blood. 2014a;124:188-195.

2. Grupp, SA, et al. Analysis of a Global Registration Trial of the Efficacy and Safety of CTL019 in Pediatric and Young Adults with Relapsed/Refractory Acute Lymphoblastic Leukemia (ALL). (2016). Blood, 128(22), 221.