On March 29, Novartis announced that the US Food and Drug Administration had accepted the company’s BLA filings for CTL019 (tisagenlecleucel-T) for the treatment of pediatric and young adult patients with relapsed and refractory B-cell acute lymphoblastic leukemia (ALL). Two days later, Kite Pharma announced that they had completed the rolling submission for their own CAR-T therapy, KTE-C19 (axicabtagene ciloleucel), for the treatment of relapsed or refractory aggressive non-Hodgkin lymphoma (NHL). Assuming that FDA grants a priority review to Kite’s drug candidate, something that Novartis had already received, both products could undergo advisory committee review and achieve US marketing approval in approximately the same timeframe.
Chimeric antigen receptor T-cell, or CAR-T therapy removes T-cells from patients and genetically engineers them to attack tumor cells expressing a specific protein. The engineered cells are then given back to the patient to attack cancerous cells. Both Novartis’ and Kite’s candidates target cells expressing CD19, a protein expressed on certain white blood cells and present in certain types of blood cell cancers.
CAR-T therapies have demonstrated some real successes against blood cell cancers. Kite recently reported full six month data from its pivotal trial for KTE-C19, which achieved an overall response rate of 82% (complete responses – 54%; partial responses – 28%). Median overall survival has not yet been reached; 80% of the patients treated remained alive after 6 months. Similarly, pivotal trial data submitted by Novartis from a global Phase 2 study of its CAR-T in ALL showed 82% of patients achieved a complete remission or a complete remission with incomplete blood cell recovery at three months after infusion.
At the same time, this powerful treatment approach is also associated with serious toxicities, as well as treatment-related deaths. Such toxicities recently led to the discontinuation of Juno’s one-time leading anti-CD19 CAR-T agent, JCAR015, when a trial of that CAR-T in ALL resulted in multiple deaths, mostly as a result of brain edema associated with the treatment.
While this set back ended Juno’s leadership in the CAR-T race, the company plans to initiate a pivotal trial of another anti-CD19 CAR-T candidate, JCAR-017, later this year in diffuse large B-cell lymphoma, as well as continue development of other anti-CD19 therapies. Bluebird bio, Bellicum, and others are also developing anti-CD19 CAR-T candidates, Bellicum is incorporating an inactivation switch technology aimed at avoiding the severe side-effects that have plagued first-generation CAR-T approaches.
Novartis and Kite are initially seeking approval for their CAR-T treatments in different applications and so will not immediately go head-to-head if approved at the same time. But that situation is unlikely to last for long, as Novartis plans to file for approval of its product in diffuse large B-cell lymphoma later this year (and will release data from its pivotal trial in that indication in June at the International Conference on Malignant Lymphoma.). In April, Novartis received a breakthrough therapy designation for that indication as well.
In any case, the first of the two companies to gain approval is likely to be able to set pricing for these drugs. Over the past year, drug pricing has become a major issue, not only within the pharmaceutical industry and with payers, but with the current Administration, Congress and the general public. We have written about the need for companies to show value and to develop innovative strategies for truly innovative medicines like the CAR-T and immuno-oncology treatments that provide real gains for at least some cancer patients. And perhaps these therapies could be priced so that insurers pay a premium for patients who go into remission.