Novartis' Kymriah (tisagenlecleucel) has achieved a significant milestone, becoming the first CAR-T therapy approved in the European Union for the treatment of relapsed or refractory follicular lymphoma (FL). This approval offers a new therapeutic avenue for patients with grade 1, 2, and 3A FL who have relapsed after two or more prior systemic therapies. The decision by the EU marks a significant advancement in the treatment landscape for this incurable disease.
Clinical Efficacy Demonstrated in ELARA Trial
The approval is rooted in the compelling results of the ELARA trial. The study demonstrated that 86% of patients treated with Kymriah experienced a response, with 69% achieving a complete response, indicating the elimination of all detectable evidence of the disease. Furthermore, the treatment effect appears to be durable, with 87% of complete responders remaining in remission for at least nine months following their initial response. These findings highlight the potential of Kymriah to provide long-lasting benefits for patients with relapsed or refractory FL.
Follicular Lymphoma: An Unmet Need
Follicular lymphoma is the second most common form of non-Hodgkin lymphoma (NHL), representing approximately 22% of NHL cases. While it is a slow-developing cancer, it remains incurable. With each subsequent line of treatment, patients often become less responsive to therapy, leading to a five-year survival rate of only 20% for those in the third line of treatment or later. This underscores the urgent need for innovative therapies like Kymriah to improve outcomes for these patients.
Kymriah's Expanding Role in Hematologic Malignancies
This approval marks the third indication for Kymriah in the EU, adding to its existing approvals for the treatment of diffuse large B-cell lymphoma (DLBCL) and acute lymphoblastic leukemia (ALL). Kymriah was the first CAR-T therapy to reach the market in 2017 and has since been a key player in the evolving landscape of cancer immunotherapy. Marie-France Tschudin, Novartis' chief commercial officer, stated, "With this approval, we are pleased to be able to offer this transformative therapy to more people across the globe living with this advanced blood cancer."
Competition in the CAR-T Space
While Novartis is currently the first to market with a CAR-T therapy for follicular lymphoma in the EU, Gilead Sciences is also seeking approval for its CAR-T therapy, Yescarta (axicabtagene ciloleucel), for the same indication. Yescarta has already been approved by the FDA for follicular lymphoma. Yescarta's application is based on the ZUMA-5 study, which reported an overall response rate of 92%, including a 75% complete response rate.
Manufacturing and Future Prospects
Oxford BioMedica, a UK-based biotech company, plays a crucial role in the manufacturing of Kymriah, serving as the sole manufacturer of the lentiviral vectors used to modify the T-cells. This collaboration highlights the complex supply chain and specialized expertise required for CAR-T therapy production. Novartis plans to continue pursuing regulatory submissions for Kymriah in pediatric and young adult patients with relapsed or refractory B-cell ALL and adult patients with relapsed or refractory DLBCL outside the US and EU.
