The FDA granted regenerative medicine advanced therapy (RMAT) designation to tisagenlecleucel (Kymriah) for an investigational new indication to treat patients with relapsed or refractory follicular lymphoma, according to Novartis, the developer of the CAR T-cell therapy.
According to a press release from Novartis, the RMAT program was developed under the 21st Century Cures Act in order to "expedite the development and review of regenerative medicine therapies intended to treat, modify, reverse, or cure a serious condition.”
The designation was granted based on preliminary clinical evidence from the ongoing phase II ELARA clinical trial, which is evaluating the safety and efficacy of tisagenlecleucel in adult patients with relapsed or refractory follicular lymphoma.
“This designation supports the advancement of Kymriah, which could potentially address an unmet need in certain patients with follicular lymphoma, as we strive to reimagine medicine at Novartis,” John Tsai, MD, head of Global Drug Development and chief medical officer at Novartis, said in a press release. “These patients are often faced with the burden of several years of various treatments as their disease continues to progress.”
ELARA is enrolling patients aged ≥18 years with 1, 2, or 3A relapsed or refractory follicular lymphoma. Exclusion criteria include CNS involvement or receiving prior anti-CD19 therapy, gene therapy, adoptive T-cell therapy, or allogeneic HSCT. Overall, the study’s target enrollment is 113 patients.
The primary endpoint for the trial is complete response (CR) rate, with secondary endpoints including overall response rate (ORR), duration of response, overall survival (OS), cellular kinetics, immunogenicity, safety, and patient-reported outcomes.
Tisagenlecleucel is designed to be a one-time treatment and is the first ever FDA-approved CAR T-cell therapy. According to the company, regulatory filing for tisagenlecleucel in relapsed or refractory follicular lymphoma is anticipated in 2021.
Should tisagenlecleucel be approved in relapsed or refractory follicular lymphoma, this will be the third indication for the therapy. Previous indications include indications in relapsed or refractory pediatric and young adult acute lymphoblastic leukemia (ALL), as well as relapsed or refractory diffuse large B-cell lymphoma (DLBCL).
The CAR T-cell therapy has been found to cause side effects that can be severe or life-threatening, such as cytokine release syndrome (CRS) or neurological toxicities. Patients who develop CRS may experience symptoms including difficulty breathing, fever, chills or shaking chills, severe nausea, vomiting and diarrhea, severe muscle or joint pain, very low blood pressure, or dizziness or lightheadedness. Additionally, patients with CRS may be admitted to the hospital and treated with other medications.
Moreover, patients with neurological toxicities may experience symptoms such as altered or decreased consciousness, headaches, delirium, confusion, agitation, anxiety, seizures, difficulty speaking and understanding, or loss of balance. Due to the risks associated with tisagenlecleucel, the therapy is only available through a restricted program under a risk evaluation and mitigation strategy (REMS) called Kymriah REMS.
According to Novartis, follicular lymphoma is the second most common form of non-Hodgkin lymphoma (NHL), representing approximately 22% of NHL cases. Further, throughout the lifetime of a patient with relapsing follicular lymphoma, they may be exposed to a median of 5 lines of prior treatment, with an upper range of 12 lines.
Novartis Kymriah receives FDA Regenerative Medicine Advanced Therapy designation in follicular lymphoma [news release]. Basel. Published April 22, 2020. novartis.com/news/media-releases/novartis-kymriah-receives-fda-regenerative-medicine-advanced-therapy-designation-follicular-lymphoma. Accessed April 22, 2020.