The US Food and Drug Administration ( FDA ) has approved Kymriah ( Tisagenlecleucel ) suspension for intravenous infusion, formerly CTL019, the first chimeric antigen receptor T cell ( CAR-T ) therapy, for the treatment of patients up to 25 years of age with B-cell precursor acute lymphoblastic leukemia ( ALL ) that is refractory or in second or later relapse.
Kymriah is a novel immunocellular therapy and a one-time treatment that uses a patient's own T cells to fight cancer.
Kymriah is the first therapy based on gene transfer approved by the FDA.
The FDA has approved a Risk Evaluation and Mitigation Strategy ( REMS ) for Kymriah.
The REMS program serves to inform and educate healthcare professionals about the risks that may be associated with Kymriah treatment.
To support safe patient access, Novartis is establishing a network of certified treatment centers throughout the country which will be fully trained on the use of Kymriah and appropriate patient care.
There has been an urgent need for novel treatment options that improve outcomes for patients with relapsed or refractory B-cell precursor acute lymphoblastic leukemia, whose prognosis is poor.
Patients often undergo multiple treatments including chemotherapy, radiation, targeted therapy or stem cell transplant, yet less than 10% of patients survive five years.
Kymriah is an innovative immunocellular therapy that is a one-time treatment. Kymriah uses the 4-1BB costimulatory domain in its chimeric antigen receptor to enhance cellular expansion and persistence.
In 2012, Novartis and the University of Pennsylvania ( Penn ) entered into a global collaboration to further research, develop and commercialize CAR-T cell therapies, including Kymriah, for the investigational treatment of cancers.
Kymriah will be manufactured for each individual patient using their own cells at the Novartis Morris Plains, New Jersey facility.
Novartis has designed a reliable and integrated manufacturing and supply chain platform that allows for an individualized treatment approach on a global scale. This process includes cryopreservation of a patient's harvested ( or leukapheresed ) cells, giving treating physicians and centers the flexibility to initiate therapy with Kymriah based on the individual patient's condition.
The FDA approval of Kymriah is based on the results of the pivotal open-label, multicenter, single-arm phase II ELIANA trial, the first pediatric global CAR-T cell therapy registration trial examining patients in 25 Centers in the US, EU, Canada, Australia and Japan.
In this study, 68 patients were infused and 63 were evaluable for efficacy.
Results have shown 83% ( 52 of 63; 95% confidence interval [ CI ]: 71%-91% ) of patients who received treatment with Kymriah achieved complete remission ( CR ) or CR with incomplete blood count recovery ( CRi ) within three months of infusion.
In addition, no minimal residual disease ( MRD ), a blood marker that indicates potential relapse, was detected among responding patients.
Median duration of remission was not reached ( 95% CI: 7.5-NE ).
The most common ( more than 20% ) adverse reactions in the ELIANA trial are cytokine release syndrome ( CRS ), hypogammaglobulinemia, infections-pathogen unspecified, pyrexia, decreased appetite, headache, encephalopathy, hypotension, bleeding episodes, tachycardia, nausea, diarrhea, vomiting, viral infectious disorders, hypoxia, fatigue, acute kidney injury and delirium.
In the study, 49% of patients treated with Kymriah experienced grade 3 or 4 cytokine release syndrome, an on-target effect of the treatment that may occur when the engineered cells become activated in the patient's body.
Cytokine release syndrome was managed globally using prior site education and implementation of the CRS treatment algorithm.
Within eight weeks of treatment, 18% of patients experienced grade 3 or 4 neurologic events. There were no incidents of cerebral edema.
The most common neurologic events were encephalopathy ( 34% ), headache ( 37% ), delirium ( 21% ), anxiety ( 13% ) and tremor ( 9% ).
Acute lymphoblastic leukemia is a cancer of the lymphocytes, a type of white blood cell involved in the body's immune system.
In people with acute lymphoblastic leukemia, the abnormal cells crowd other types of cells in the bone marrow, preventing the production of red blood cells, other types of white blood cells and platelets.
As a result, those with acute lymphoblastic leukemia may be anemic, more likely to get infections and bruise or bleed easily.
Acute lymphoblastic leukemia comprises approximately 25% of cancer diagnoses among children under 15 years old and is the most common childhood cancer in the US. ( Xagena )
Source: Novartis, 2017