FDA Approves Novartis’ CAR-T Drug, First Gene Therapy Approval in US

On Aug. 30, 2017, FDA approved Kymriah (tisagenlecleucel), Novartis’ chimeric antigen receptor T cell (CAR-T) therapy, for treating a form of acute lymphoblastic leukemia (ALL). This marks the first CAR-T therapy, as well as the first therapy based on gene transfer, to be approved by FDA in the United States, according to press releases by FDA and Novartis.

Kymriah is a genetically modified autologous T-cell immunotherapy that is a one-time treatment. Each dose is a customized treatment created using an individual patient’s own T-cells. 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 CAR protein. The genetic modification directs the T-cells to target and kill leukemia cells with a specific antigen, in this case, antigen CD19, on the surface. Once the cells are modified, they are infused back into the patient to kill the cancer cells.

“We’re entering a new frontier in medical innovation with the ability to reprogram a patient’s own cells to attack a deadly cancer,” said FDA Commissioner Scott Gottlieb, MD, in the agency press release. “New technologies such as gene and cell therapies hold out the potential to transform medicine and create an inflection point in our ability to treat and even cure many intractable illnesses. At the FDA, we’re committed to helping expedite the development and review of groundbreaking treatments that have the potential to be life-saving.”

Kymriah uses the 4-1BB costimulatory domain in its CAR to enhance cellular expansion and persistence. In 2012, Novartis and the University of Pennsylvania (Penn) formed a global collaboration to further research, develop, and commercialize CAR-T cell therapies, including Kymriah, for the investigational treatment of cancers.

"At Novartis, we have a long history of being at the forefront of transformative cancer treatment," said Joseph Jimenez, CEO of Novartis, in the company press release. "Five years ago, we began collaborating with the University of Pennsylvania and invested in further developing and bringing what we believed would be a paradigm-changing immunocellular therapy to cancer patients in dire need. With the approval of Kymriah, we are once again delivering on our commitment to change the course of cancer care."

"This therapy is a significant step forward in individualized cancer treatment that may have a tremendous impact on patients' lives," said Carl June, MD, the Richard W. Vague professor of immunotherapy, director of the Center for Cellular Immunotherapies in Penn's Perelman School of Medicine, who is a pioneer of this new treatment. "Through our collaboration with Novartis, we are creating the next wave of immunocellular cancer treatments, and are eager to progress CAR-T therapy in a host of hematologic and other cancer types."

Novartis plans additional filings for Kymriah in the US and European Union later this year, including applications with 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.

Further Collaboration

Novartis also announced 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 also 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.

Kymriah will be manufactured for each individual patient using their own cells at the Novartis Morris Plains, NJ facility, which the company acquired from Dendreon in December 2012 for $43 million. 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 cells, giving treating physicians and centers the flexibility to initiate therapy with Kymriah based on the individual patient's condition.

Novartis has demonstrated a reproducible product based on its experience manufacturing CAR-T cells for over 250 patients from 11 countries across various indications. The company 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 to support the anticipated demand from patients.

Source: Novartis and FDA