Novartis AG Receives First Ever FDA Approval for CAR-T

A new era in cancer treatment is now here. The US FDA recently gave the nod to Switzerland-based Novartis AG for its gene therapy cancer treatment, a first in the US.

Novartis’ CAR-T treatment for certain pediatric and young adult patients with a form of acute lymphoblastic leukemia (ALL) is a first-of-its-kind in the US. It is the first therapy based on gene transfer approved by the FDA. The FDA announced approval of Kymriah (tisagenlecleucel) about a month ahead of its PDUFA (Prescription Drug User Fee Act) date. Kymriah has been approved to treat patients up to 25 years of age with B-cell precursor ALL that is refractory or in second or later relapse.

Commissioner Scott Gottlieb hailed the Novartis treatment. He said gene therapy treatments such as CAR-T “hold out the potential to transform medicine and create an inflection point in our ability to treat and even cure many intractable illnesses.”

Novartis Chief Executive Officer Joe Jimenez touted the company for leading the way with CAR-T treatments. He said the company has a long history of being at the forefront of transformative cancer treatments.

“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.”

Kymriah is a genetically modified autologous T-cell immunotherapy. It is a one-time treatment. Kymriah uses the 4-1BB costimulatory domain in its chimeric antigen receptor to enhance cellular expansion and persistence. Chimeric Antigen Receptor T-Cell Therapies (CAR-T) are engineered in a laboratory to recognize a specific antigen in a cell and then administered into a cancer patient. The CAR-T cells should, if all goes as planned, multiply within the body and target the antigen and eliminate the threat.

Throughout clinical trials Novartis’ CAR-T treatment showed tremendous promise. In December, the company announced Kymriah, known at the time as CLT019, sent 82% percent of patients’ blood cancer into remission, according to interim data presented at the American Society of Hematology meeting. Overall remission rates for patients within 3 months of treatment was 83% during trials, the FDA recently said.

Pricing has yet to be set for the treatment, but it’s sure to be high. The company has not yet announced its pricing, but when it shared news of the FDA’s approval, Novartis said it is committed to ensuring eligible patients have access to the drug. Novartis is providing traditional support to patients by helping them navigate insurance coverage and providing financial assistance for those who are uninsured or underinsured, the company said.

Although Kymriah is being hailed as a breakthrough treatment, the gene therapy will come with a black box warning. CAR-T treatments have been associated with cytokine release syndrome (CRS), which is a systemic response to the activation and proliferation of CAR T-cells causing high fever and flu-like symptoms, as well as severe neurological events. Throughout Novartis’ various trials, about half the patients experienced grade 3 or 4 CRS. Some patients taking CAR-T treatments have died from brain swelling associated with CRS. Rival CAR-T company Juno Therapeutics shut down one trial due to CRS deaths. To mitigate CRS, Novartis said the FDA is requiring that hospitals and their associated clinics that dispense Kymriah be specially certified.

Alongside Kymriah, the FDA approved Genentech’s Actemra (tocilizumab) to treat CAR T-cell-induced severe or life-threatening CRS in patients 2 years of age or older. The FDA said 69% of patients had complete resolution of CRS within 2 weeks following 1 or 2 doses of Actemra.

While Novartis celebrates, another CAR-T treatment is awaiting FDA approval. Kite Pharma, which was recently acquired by Gilead Sciences for $12 billion, is champing at the bit to be the second company to move forward with a CAR-T treatment. In May, Kite received priority review from the FDA for its CAR-T treatment, axicabtagene ciloleucel. The US FDA is set to make a decision on Nov. 29 for the treatment of patients with refractory aggressive non-Hodgkin lymphoma (NHL).