' REMS Helps A Speedy Launch of CAR-T Cell Therapy | MTTLR

REMS Helps A Speedy Launch of CAR-T Cell Therapy

I first learned of CAR-T cell therapy in 2015 while working in an immunology lab. It immediately caught my attention as a brilliant, unconventional cancer treatment: it modifies a patient’s own T cells and enlists them to fight cancer. T cells can recognize non-self antigens presented on a cell’s surface, label those cells exogenous, and eliminate them. Scientists have developed CAR-T cell therapy by utilizing these unique characteristics of T cells.

Over the past five years, CAR-T cell therapy has made a breakthrough march from bench to bedside. On August 30, 2017, after only seven-month’s review, the Food and Drug Administration (FDA) approved Novartis’ Kymriah, the first CAR-T cell treatment. Kymriah is developed to treat patients up to 25-year-old with relapsed or refractory acute lymphoblastic leukemia (ALL). In October of the same year, the FDA approved the second CAR-T cell therapy, Yescarta. On May 1, 2018, the FDA expanded the use of Kymriah to adult patients with certain types of non-Hodgkin lymphoma.

Kymriah and Yescarta are based on the same scientific concept and innovation. Patients’ T cells are engineered by a virus to recognize the CD-19 molecule, a surface bio-marker of both normal and cancerous B cells. These T cells are expanded in vitro and infused back into patients’ blood. Once in the blood of patients, bio-engineered T cells can recognize, attack, and clear B cells which express the CD-19 molecule.

Because of its risk and cost, CAR-T cell therapy is generally a last resort. But for cancer patients who have not been successful with conventional treatments, it is a source of great hope. More CAR-T cell therapies are in development. According to the FDA Commissioner Scott Gottlieb,[1] there were 76 active INDs related specifically to CAR-T cell products under FDA review in 2017. CAR-T cell therapies are risky because they cannot selectively target cancerous B cell subsets, but wipe out the entire B cell population, both normal and cancerous.

The FDA has approved both Kymriah and Yescarta subject to Risk Evaluation and Mitigation Strategy (REMS), in order to limit the risk of severe side effects. The general practice of the FDA is to perform only pre-market approval and labeling. Once a drug is approved, the FDA usually lacks the authority to regulate post-market activities. The REMS program is different because it empowers the FDA to regulate some post-market activities in exchange for pre-market approval. Under REMS, providers must continue to monitor and report patients with side effects.

Cytokine Release Syndrome (CRS), a side effect, can be fatal or life-threatening. It occurred in 79% of the patients enrolled in the clinical trial. To reach its goals under the  REMS program, Novartis needs to ensure that “hospitals and their associated clinics that dispense Kymriah are specially certified and have on-site, immediate access to tocilizumab”, an effective immunosuppressor to dampen CRS and “those who prescribe, dispense, or administer Kymriah are aware of how to manage the risks of cytokine release syndrome and neurological toxicities.”

In addition, the high cost of the two approved CAR-T cell treatments restricts patient access. Current prices for CAR T-cell therapies are between $373,000 and $475,000 for a one-time treatment, leaving insurers struggling to pay. Indeed, the former FDA Commissioner expressed his concerns: “I’m extremely worried that if we don’t adapt the approach to reimbursement soon, we may foreclose the therapeutic opportunities.”

The approval of CAR-T cell therapy marks a milestone in personalized medicine and transforms the cancer therapy landscape. How to provide insurance coverage and how to manage risks prophylactically and react swiftly to materialized risks are unanswered questions that may call for modification and improvement of the current FDA regulatory scheme.

Submit a Comment

Your email address will not be published. Required fields are marked *