Kymriah (tisagenlecleucel) for the Treatment of Acute Lymphoblastic Leukaemia, United States of America
Kymriah (tisagenlecleucel) is the first chimeric antigen receptor T cell (CAR-T) therapy approved in the US for the treatment of paediatric and young adult patients with B-cell precursor acute lymphoblastic leukaemia (ALL).
The drug was first developed by Penn using the 4-1BB costimulatory domain for enhancing cellular responses, while Novartis joined as a co-developer as part of a development contract.
Novartis' Biologics License Application (BLA) for Kymriah was accepted for review by the US Food and Drug Administration (FDA) in March 2017.
The FDA granted breakthrough therapy designation to the drug in April 2017.
It also received PRIority MEdicines (PRIME) designation from the European Medicines Agency (EMA) in 2016.
The FDA's Oncologic Drugs Advisory Committee (ODAC) unanimously recommended Kymriah's approval in July 2017, and the drug subsequently received full FDA approval in August 2017.
Acute lymphoblastic leukaemia (ALL)
Acute lymphoblastic leukaemia (ALL) is a type of cancer that occurs due to uncontrolled growth of white blood cells, which crowd other types of cells in the bone marrow and prevent production of red blood cells and platelets.
The disease causes patients to become anaemic and prone to infections and bruises or bleed easily.
The risk of developing ALL is highest in children younger than five years.
ALL is estimated to account for 25% of cancer diagnoses among children under 15 years old in the US.
Kymriah's mechanism of action
Kymriah is a chimeric antigen receptor T cell (CAR-T) therapy, which re-programmes the patient's T cells with a transgene encoding a chimeric antigen receptor (CAR), while identifying and removing CD19-expressing malicious cells.
The drug is available in 10ml to 50ml suspension per bag and can be administered through intravenous (IV) infusion.
Clinical trials on Kymriah
FDA approval of Kymriah was based on the results obtained from a pivotal open-label, multi-centre, single-arm phase II clinical trial named ELIANA.
The trial was conducted across 25 centres located in the US, EU, Canada, Australia and Japan, and saw a total of 88 patients infused with Kymriah.
The study demonstrated that 83% of the patients treated with Kymriah achieved complete remission (CR) with incomplete blood count recovery (CRi) within three months of infusion.
Results also indicated that 63 patients treated with Kymriah demonstrated relapse-free survival at six months.
Additionally, the study showed that the patients had no minimal residual disease (MRD), which is an indicator for potential relapse detected among responding patients.
The most common adverse reactions encountered during the clinical study were cytokine release syndrome (CRS), hypogammaglobulinemia, unspecified pathogen infections, pyrexia, decreased appetite, headache, encephalopathy, hypotension, and bleeding episodes.
Other adverse reactions included tachycardia, nausea, diarrhoea, vomiting, viral infectious disorders, hypoxia, fatigue, acute kidney injury, and delirium.
Marketing commentary on Novartis
Novartis is a leading innovative healthcare solutions provider headquartered in Basel, Switzerland.
The company offers innovative medicines, cost-saving generic and biosimilar pharmaceuticals, and eye care. Novartis' products are sold in more than 155 countries.
Novartis and Penn originally entered a development contract in 2012, which led to the two companies agreeing to carry out the development and commercialisation of CAR-T cell therapies, including Kymriah.
The commercial manufacturing of Kymriah will be carried out at Novartis' manufacturing facility in Morris Plains, New Jersey.