- The Food and Drug Administration on Wednesday approved the first CAR-T therapy, ushering in a new approach to treating cancer in a landmark decision for the rapidly advancing field of cell therapy.
- Treatment with the therapy, developed by Swiss pharma Novartis AG, led to remarkable results in children with an aggressive form of leukemia resistant to other drugs.
- Novartis' CAR-T treatment, which will be marketed as Kymriah, leads an emerging field of cell therapies designed to engineer the body's immune cells to seek out and destroy cancers. Novartis priced Kymriah at $475,000 per patient and other CAR-Ts in development are expected to be similarly expensive.
Development of CAR-T has progressed rapidly in short order, showing strong data in clinical trials that indicate the therapies could be a significant advance for patients with hard-to-treat blood cancers.
"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," wrote FDA Commissioner Scott Gottlieb in a statement on the approval.
The FDA approved Kymriah (tisagenlecleucel) for patients up to 25 years of age who have refractory B-cell precursors acute lymphoblastic leukemia that has relapsed at least twice. Roughly 3,100 patients in the U.S. are diagnosed with B-cell ALL, but only about 600 or so fall under Kymriah's label.
ALL patients who relapse, particularly if following a stem cell transplant, have a poor prognosis with an estimated two year survival rate of 15%.
In a pivotal Phase 2 study, Kymriah led to complete remission in 83% (52 out of 63 patients) within three months of infusion — a major step-up on current treatment options for this patient population.
Unlike other drugs for cancer, CAR-T is designed to be given just once. While clinical studies have shown some patients will still relapse even after CAR-T treatment, others have experienced remissions that last years.
Novartis' Kymriah is the first CAR-T therapy to be reviewed by the FDA, winning the unanimous backing of an independent panel in early July. Another CAR-T treatment, made by Kite Pharma, Inc., could also soon win approval from the regulator for treatment of lymphoma in adults. Just this week, Gilead Sciences, Inc. said it would acquire Kite Pharma for $11.9 billion, highlighting the promise of the CAR-T field.
"Two years ago many people would have told you these types of treatments were science fiction, and now one is approved at FDA," said Brad Loncar, founder of a cancer immunotherapy exchange-traded fund.
"Being the first approval of its kind, I expect this to be the beginning of a new era using these types of treatments. That was reflected in the Gilead deal this week and I do think you will see much more investment in the field."
One of the largest questions surrounding CAR-T up until now has been what these one-time treatments will cost. CAR-T's personalized nature, as well as the high manufacturing costs associated with producing each treatment, mean pricing CAR-T is more challenging than that of other cancer drugs.
Novartis said on a call with reporters Wednesday it would price Kymriah at $475,000 per patient, instantly making it one of the most expensive medicines in the world.
Other treatments, such as GlaxoSmithKline plc's gene therapy Strimvelis, cost more. But Kymriah is aimed at treating many more patients, raising pressing questions about how to value a treatment that could dramatically extend survival for some.
In an effort to mitigate these concerns, Novartis will collaborate with the Centers for Medicare and Medicaid Services (CMS) to provide Kymriah under an outcomes-based approach which will allow for payment only if patients respond to treatment by the end of the first month. For patients who don't respond, Novartis won't charge for treatment and will absorb the cost of manufacturing.
The company made particular note that its analysis of the market before Kymriah's approval indicated a cost-effective price would be between $600,000 and $750,000 per patient. Kymriah's price comes in below that range but still presents a hefty upfront cost for insurers to swallow.
The Swiss pharma will roll out a patient access program to help patients who are unable to secure coverage for Kymriah, although executives said they expect the vast majority of patients eligible for treatment will be covered by insurance.
Some patients treated with CAR-T also go onto receive a stem cell transplant, which adds in further cost. Novartis says the goal of Kymriah is to eliminate the need for transplant and move towards being a true one-time treatment.
Another further complication are the drugs needed to help manage the potentially severe side effects associated with CAR-T. Actemra (tocilizumab), an IL-6 inhibitor made be Roche AG's Genentech unit, is commonly used in patients who experience cytokine release syndrome (CRS). In approving Kymriah, the FDA also broadened the label of Actemra to specifically use treating CRS in the context of CAR-T treatment.
Novartis said the collaboration with CMS could potentially support lower prices for future indications if the value delivered is lower. The company plans to seek approval of Kymriah in a type of non-Hodgkin lymphoma known as diffuse large B-cell lymphoma later this year. Remission rates in that population have been lower than in ALL, which could translate to a lower price in that indication.