FDA: Actemra for the treatment for severe or life-threatening cytokine release syndrome induced by CAR T cell therapy
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.
Cytokine release syndrome, 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.
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.
The study population included 45 pediatric and adult patients treated with Actemra, with or without additional high-dose corticosteroids, for severe or life-threatening cytokine release syndrome.
Thirty-one patients ( 69%; 95% CI: 53%–82% ) achieved a response, defined as resolution of cytokine release syndrome 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.
A second study confirmed resolution of cytokine release syndrome within 14 days using an independent cohort that included 15 patients with CAR T cell-induced cytokine release syndrome.
The FDA granted Priority Review and Orphan Drug Designation to Actemra for the treatment of CAR T cell-induced cytokine release syndrome based on the rare, severe and life-threatening nature of cytokine release syndrome 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.
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.
Cytokine release syndrome, 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 cytokine release syndrome 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.
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 rheumatoid arthritis in 41 countries.
The Actemra RA subcutaneous clinical development program included two phase III clinical studies and enrolled more than 1,800 people with rheumatoid arthritis 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 ). ( Xagena )
Source: Genentech, 2017