Roche's RoActemra gains positive CHMP opinion for CAR T-cell-induced cytokine release syndrome

• Cytokine release syndrome (CRS), a severe and life-threatening condition, is caused by an overactive immune response and is often associated with the use of chimeric antigen receptor (CAR) T-cell therapy for certain blood cancers
  
  
• RoActemra would be the first approved treatment for CRS in Europe

           
Basel, 29 June 2018 - Roche (SIX: RO, ROG; OTCQX: RHHBY) announced today that the Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion recommending approval of RoActemra® (tocilizumab) for the treatment of cytokine release syndrome (CRS), in adults and pediatric patients aged two years and older. CRS is a potentially severe and life-threatening side effect of chimeric antigen receptor (CAR) T-cell therapy for certain blood cancers.^[1]

A final decision regarding the approval and label of RoActemra for the treatment of CRS is expected from the European Commission in the near future. RoActemra would be the first approved treatment of CAR T-cell-induced CRS in Europe.

"Cytokine release syndrome, which is triggered by an overactive immune response, causes life-threatening symptoms, such as cardiac dysfunction and multi-organ failure," said Sandra Horning, MD, Roche's Chief Medical Officer and Global Head of Product Development. "Today's CHMP opinion marks an important step towards providing the first approved option for patients in Europe suffering from these severe symptoms as a result of their cancer treatment."

The positive opinion is based on a retrospective analysis of clinical trial data generated by Kite and Novartis, two manufacturers of CAR T-cell therapies for blood cancers. RoACTEMRA was used to treat CAR T-cell therapy-induced CRS during these trials.^[2,3,4] The study population included 51 pediatric and adult patients treated with RoActemra, with or without additional high-dose corticosteroids, for severe or life-threatening CRS. Thirty-nine patients (76.5%; 95% CI: 62.5%-87.2%) achieved a response, defined as resolution of CRS within 14 days of the first dose of RoActemra, if no more than two doses of RoActemra were needed, and no drugs other than RoActemra and corticosteroids were used for treatment. No adverse reactions related to RoActemra 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 (53% responded).

Actemra was approved for the treatment of CAR T-cell-induced CRS by the US Food and Drug Administration in August 2017, following Priority Review and Orphan Drug Designation.



About CAR T-cell Therapy-Induced Cytokine Release Syndrome
CAR T-cell therapies are designed for the treatment of certain blood 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/RoActemra (tocilizumab)
Actemra/RoActemra is the first approved anti-IL-6 receptor biologic available in both intravenous (IV) and subcutaneous (SC) formulations for the treatment of adult patients with moderate-to-severe active rheumatoid arthritis (RA). Actemra/RoActemra can be used alone or with methotrexate (MTX) in adult RA patients who are intolerant to, or have failed to respond to, other disease-modifying anti-rheumatic drugs (DMARDs). In Europe, RoActemra IV and SC are also approved for use in adult patients with severe, active and progressive RA who previously have not been treated with MTX. Actemra/RoActemra IV formulation is approved globally for polyarticular juvenile idiopathic arthritis (pJIA) and systemic juvenile idiopathic arthritis (sJIA) in children two years of age and older. Actemra/RoActemra SC injection is also the first approved therapy for the treatment of giant cell arteritis (GCA) in more than 40 countries, including the US and Europe.  In the US, Actemra IV injection is approved for the treatment of chimeric antigen receptor (CAR) T-cell-induced severe or life-threatening cytokine release syndrome (CRS) in people two years of age and older. Actemra is the first approved treatment for CRS in this setting. In Japan, Actemra is also approved for the treatment of Castleman's Disease and Takayasu Arteritis. Actemra/RoActemra is part of a co-development agreement with Chugai Pharmaceutical Co., Ltd and has been approved in Japan since April 2005. Actemra/RoActemra is approved in more than 110 countries worldwide.

Actemra was granted Orphan Drug Designation and Breakthrough Therapy Designation for SSc by the US Food and Drug Administration in April 2013 and June 2015 respectively.

About Roche
Roche is a global pioneer in pharmaceuticals and diagnostics focused on advancing science to improve people's lives. The combined strengths of pharmaceuticals and diagnostics under one roof have made Roche the leader in personalised healthcare - a strategy that aims to fit the right treatment to each patient in the best way possible.

Roche is the world's largest biotech company, with truly differentiated medicines in oncology, immunology, infectious diseases, ophthalmology and diseases of the central nervous system. Roche is also the world leader in in vitro diagnostics and tissue-based cancer diagnostics, and a frontrunner in diabetes management.
Founded in 1896, Roche continues to search for better ways to prevent, diagnose and treat diseases and make a sustainable contribution to society. The company also aims to improve patient access to medical innovations by working with all relevant stakeholders. Thirty medicines developed by Roche are included in the World Health Organization Model Lists of Essential Medicines, among them life-saving antibiotics, antimalarials and cancer medicines.


Roche has been recognised as the Group Leader in sustainability within the Pharmaceuticals, Biotechnology & Life Sciences Industry nine years in a row by the Dow Jones Sustainability Indices (DJSI).

The Roche Group, headquartered in Basel, Switzerland, is active in over 100 countries and in 2017 employed about 94,000 people worldwide. In 2017, Roche invested CHF 10.4 billion in R&D and posted sales of CHF 53.3 billion. Genentech, in the United States, is a wholly owned member of the Roche Group. Roche is the majority shareholder in Chugai Pharmaceutical, Japan. For more information, please visit www.roche.com.

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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). Blood. 2016; 128(22): 221.

[3] Le RQ, et al. FDA approval summary: tocilizumab for treatment of chimeric antigen receptor T cell-induced severe or life-threatening cytokine release syndrome. The Oncologist. 2018; 23:1-5.

[4] FDA.gov. (2018). Center for drug evaluation and research. Multi-discipline review [Internet; cited 2018 June]. Available at: https://protect eu.mimecast.com/s/uFE0Cj7DfGon5BuR0BIE?domain=accessdata.fda.gov.