October 27, 2021: “Novartis announced that the US FDA and EMA have accepted the company’s Supplemental Biologics License Application (sBLA) and Type II Variation, respectively, for Kymriah® (tisagenlecleucel) in adult patients with relapsed or refractory (r/r) follicular lymphoma (FL) after two prior lines of treatment.
The FDA has also granted priority review to the company’s sBLA for Kymriah in adult patients with r/r FL. Kymriah was previously granted orphan medicinal product designation by the European Commission (EC) for FL.
If approved in this potential third indication, Kymriah would have the opportunity to present an important treatment option for those patients with r/r FL in need of potentially definitive outcomes.
The regulatory submissions are based on positive data from the pivotal Phase II ELARA trial, which investigated the efficacy and safety of Kymriah in adult patients with r/r FL.
The trial met the primary endpoint with robust responses observed in heavily pretreated patients.
The safety profile was remarkable, with no patients experiencing grade 3 or higher cytokine release syndrome (CRS) related to Kymriah within the first 8 weeks following infusion.
Data from the trial was presented earlier this year as an oral presentation during the 2021 Annual American Society of Clinical Oncology (ASCO) Virtual Scientific Meeting.
“This is an important milestone in our mission to bring Kymriah to adult patients with relapsed or refractory follicular lymphoma. Receiving orphan drug designation from the EC as well as priority review from the FDA underscores the unmet need and urgency for these patients.
With Kymriah demonstrating impressive results in the ELARA trial, we are hopeful that we can offer a unique and potentially definitive treatment that minimizes the burden,” said Jeff Legos, Executive Vice President, Global Head of Oncology & Hematology Development, Novartis.
Orphan drug designation is reserved for medicines that treat, prevent or diagnose a life-threatening or chronically debilitating rare disease with a prevalence in the EU of below 5 in 10,000 and with either no currently approved method of diagnosis, prevention or treatment or with significant benefit to those affected by the disease.
The decision follows a positive opinion from the Committee for Orphan Medicinal Products (COMP) of the EMA.
Kymriah also has Orphan Drug designation from the FDA and the Japan Ministry of Health, Labour and Welfare (MHLW) for this disease.
Priority Review is granted to therapies that have the potential to provide significant improvements in the treatment, diagnosis or prevention of serious conditions, as determined by the FDA.
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Kymriah is currently approved by the FDA, EMA and other regulatory authorities for the treatment of r/r pediatric and young adult (up to and including 25 years of age) acute lymphoblastic leukemia (ALL), and r/r adult diffuse large B-cell lymphoma (DLBCL).
About follicular lymphoma
Follicular lymphoma (FL), the second most common form of non-Hodgkin lymphoma (NHL), is an indolent lymphoma, and represents approximately 22% of NHL cases.
It is often an unrelenting malignancy with a relapsing and remitting pattern.
Throughout the lifetime of a patient with relapsing FL, he or she may be exposed to a median of five lines of prior treatment, with an upper range of 13 lines.
Although patients in in third or later line treatment for FL have multiple systemic therapies available, the efficacy of these regimens drops off rapidly in later lines.
Additionally, because of this relapsing and remitting pattern, patients who are refractory to treatment or relapse may exhaust available treatment options.
About the ELARA trial
ELARA is a Phase II, single-arm, multicenter, open-label trial investigating the efficacy and safety of Kymriah in adult patients with r/r FL after at least two prior therapies. This international trial has enrolled patients from over 30 sites in 12 countries worldwide.
The primary endpoint is complete response rate (CRR) based on best response by central review (Lugano 2014 criteria). Patients evaluable for efficacy had measurable disease at infusion and more than six months of follow-up from infusion or discontinued early.
After infusion, disease assessments were performed every three months. Secondary endpoints include overall response rate, duration of response, progression-free survival, overall survival and safety.
Primary analysis data announced at ASCO 2021 showed Kymriah led to responses for the majority of patients treated, with 66% achieving a complete response (95% CI, 56-75). The overall response rate was 86% (95% CI, 78-92).
Importantly, no patients in ELARA trial experienced grade 3 or higher cytokine release syndrome related to Kymriah within the first 8 weeks following infusion, the most common side effect associated with CAR-T therapy.”
