The US Food and Drug Administration (FDA) has approved Novartis’ cancer treatment, Kymriah (tisagenlecleucel), as the first chimeric antigen receptor T cell (CAR-T) therapy available in the US. The approval was for certain pediatric and young adult patients with a form of acute lymphoblastic leukemia (ALL).
Kymriah is a customized treatment created using an individual patient’s own T-cells, a type of white blood cell known as a lymphocyte. The patient’s T-cells are collected and sent to a manufacturing center where they are genetically modified to include a new gene that contains a specific protein (a CAR) that directs the T-cells to target and kill leukemia cells that have a specific antigen (CD19) on the surface. Once the cells are modified, they are infused back into the patient to kill the cancer cells, according information from the FDA.
Novartis plans additional filings for Kymriah in the US and European Union (EU) later in 2017, including applications with the FDA and European Medicines Agency, for treating adult patients with relapsed-refractory diffuse large B-cell lymphoma. Additional filings beyond the US and EU are anticipated in 2018.
Kymriah will be manufactured for each patient using his/her own cells at Novartis’ facility in Morris Plains, New Jersey. Novartis has designed an 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. Novartis says it has developed a reproducible product with having manufactured CAR-T cells for more than 250 patients from 11 countries across various indications. Novartis continues to advance its CAR-T manufacturing expertise in Morris Plains, where it has been supplying CAR-T cells for global clinical trials and where it continues to invest in support of anticipated demand.
In support of the product, Novartis has formed a collaboration with the US Centers for Medicare and Medicaid Services (CMS) focused on improving efficiencies in current regulatory requirements to deliver value-based care and ensure access for this specific patient population. This approach is intended to include indication-based pricing for medicines and supports payments for a medicine, such as Kymriah for its initial indication, based on the clinical outcomes achieved, which would eliminate inefficiencies from the healthcare system. Other value-based approaches related to future indications for Kymriah and CAR-T cell therapies are under discussion. Novartis is further collaborating with CMS to make an outcomes-based approach available to allow for payment only when pediatric and young adult ALL patients respond to Kymriah by the end of the first month. Future potential indications would be reviewed for the most relevant outcomes-based approach.
Novartis developed its CAR T therapy in collaboration. 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. In February 2016, Novartis and Penn opened a center for advanced cellular therapeutics on the Penn campus, which was constructed in part through a $20-million investment from Novartis.
Kite Pharma, a Santa Monica, California-headquartered cell therapy company, is also advancing a late-stage CAR-T therapy, axicabtagene ciloleucel, which is under regulatory review by the FDA and the European Medicines Agency for treating refractory aggressive non-Hodgkin lymphoma, which includes diffuse large B-cell lymphoma, transformed follicular lymphoma, and primary mediastinal B-cell lymphoma. Some analysts have projected near blockbuster status for the drug. A recent analysis by Clarivate Analytics projects sales of more than $900 million in 2021. Earlier this week in August 2017, Gilead Sciences agreed to acquire Kite Pharma for $11.9 billion, in a deal that is expected to close in the fourth quarter of this year.
Source: Novartis and FDA