Novartis' CAR-T Therapy, CTL019, Approved 10-0 by FDA's ODAC

The potentially revolutionizing gene therapy treatment, considered the next frontier in cancer care, just got a step closer to approval. A chimeric antigen receptor-T (CAR-T) cell treatment developed by Novartis—tisagenlecleucel or CTL019—was unanimously approved 10-0 by FDA’s Oncologic Drugs Advisory Committee (ODAC) for the treatment of children and young adults with relapsed or refractory B-cell acute lymphoblastic leukemia.

A partnership between Novartis and the University of Pennsylvania resulted in the development of CTL019 and pushed the commercialization of CAR-T treatment, which involves reengineering a patient’s own white blood cells to attack the tumor cells. Jae Park, MD, a hematologist-oncologist at the Memorial Sloan Kettering Cancer Center in New York, who is leading a clinical trial using CAR-T cells, told The American Journal of Managed Care^® in an interview in February that he is very excited about the impact of using immunotherapy and manipulating the body’s immune system, unlike chemotherapy (which is non-specific) or oral targeted treatments (which can develop resistance).

The phase 2 ELIANA study found 82% of patients reached complete remission or complete remission with incomplete blood count recovery at 3 months following CTL019 treatment.

A significant concern with this treatment, however, has been the management of adverse effects: cytokine release syndrome (CRS) and neurological toxicity. According to FDA’s briefing document, the company has a communication plan in place as their Risk Evaluation and Mitigation Strategy (REMS), which includes:

• A Dear Healthcare Provider Letter to pediatric oncologists and transplant specialists
• REMS factsheet
• CRS Management Algorithm
• Patient wallet card
• REMS website

Long-term safety monitoring proposed by Novartis includes an observational long-term follow-up study in patients who receive CTL019, the details of which can be found in the briefing document. To this end, a significant portion of the ODAC’s discussion today included the length of time that the study would be conducted for. The FDA wants the company to follow patients who are part of the investigational new drug study with CTL019 for 15 years to monitor subsequent malignant transformation, which would require the creation of a patient registry.

Today’s committee approval now sets the company on track for an FDA review, and subsequent decision, in October. If approved, Novartis plans to make the treatment available at 30 sites, each trained in the multi-step process of harvesting cells, handling the product, and treating patients for the accompanying severe immune response.

Kite, Novartis’ competitor in the field, is expected to hear from the FDA a month later, in November, on its CAR-T treatment for adults with advanced lymphoma.

According to Park, “A lot of efforts are being invested to improve the safety and efficacy of CAR-T cells, so we do expect the emergence of better and safer therapies in the future, either in combination treatments or by further modification of CAR-T cells, to hopefully lead us to a 'cure' for cancer.”