Novartis receives priority review by US FDA and filing acceptance by EMA for Kymriah to treat patients with relapsed or refractory follicular lymphoma
Novartis today announced that the US Food and Drug Administration (FDA) and the European Medicines Agency (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 infusion1. 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 disease3. 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 FDA4.
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 cases5,6. It is often an unrelenting malignancy with a relapsing and remitting pattern7,2. 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 lines8,9. 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 lines2. Additionally, because of this relapsing and remitting pattern, patients who are refractory to treatment or relapse may exhaust available treatment options2.
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)1. 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 therapy1.
About Novartis Commitment to Oncology Cell & Gene
Novartis has a mission to reimagine medicine by bringing curative cell & gene therapies to patients worldwide. Novartis has a deep CAR-T pipeline and ongoing investment in manufacturing and supply chain process improvements. With active research underway to broaden the impact of cell and gene therapy in oncology, Novartis is going deeper in hematological malignancies, reaching patients with other cancer types and evaluating next-generation CAR-T cell therapies that focus on new targets and utilize new technologies.
Novartis was the first pharmaceutical company to significantly invest in pioneering CAR-T research and initiate global CAR-T trials. Kymriah, the first approved CAR-T cell therapy, developed in collaboration with the Perelman School of Medicine at the University of Pennsylvania, is the foundation of Novartis? commitment to CAR-T cell therapy.
Kymriah is currently approved for use in at least one indication in 30 countries and at more than 345 certified treatment centers, with the ambition for further expansion to help fulfill the ultimate goal of bringing CAR-T cell therapy to every patient in need.
Novartis has an expansive global CAR-T manufacturing footprint that includes both Novartis-owned and contract manufacturing sites. This comprehensive, integrated footprint strengthens the flexibility, resilience and sustainability of the Novartis manufacturing and supply chain.
Important Safety information from the Kymriah SmPC
Kymriah (tisagenlecleucel) is an autologous, immunocellular cancer therapy which involves reprogramming a patient's own T-cells with a transgene encoding a chimeric antigen receptor (CAR) to identify and eliminate CD19-expressing cells. It is administered as intravenous infusion.
Kymriah is indicated for the treatment of pediatric and young adult patients up to and including 25?years of age with B-cell acute lymphoblastic leukemia (ALL) that is refractory, in relapse post-transplant or in second or later relapse as well as for adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) after two or more lines of systemic therapy.
Kymriah must not be administered in case of hypersensitivity to the active substance or to any of the excipients of the product. In addition, contraindications of the lymphodepleting chemotherapy that is usually preceding the Kymriah infusion to prepare the patient's body, must be considered.
For details, please see the Summary of Product Characteristics (SmPC).
Reasons to delay Kymriah treatment
Kymriah treatment should be delayed, if a patient has any of the following conditions:
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- Unresolved serious adverse reactions (especially pulmonary reactions, cardiac reactions or hypotension) from preceding chemotherapies.
- Active uncontrolled infection.
- Active graft-versus-host disease (GVHD).
- Significant clinical worsening of leukemia burden or lymphoma following lymphodepleting chemotherapy.
- Schuster, S. et.al. Efficacy and Safety of Tisagenlecleucel (Tisa-cel) in Adult Patients (Pts) With Relapsed/Refractory Follicular Lymphoma (r/r FL): Primary Analysis of the Phase 2 ELARA Trial. Abstract #7508. 2021 American Society of Clinical Oncology (ASCO) Annual Meeting, June 4-8, Chicago, IL.
- Sutamtewagul, G. & Link, B.K. Novel treatment approaches and future perspectives in follicular lymphoma.?Ther Adv Hematol.?2019; 10:1?20.
- European Medicines Agency. Orphan Designation Overview. Accessed August 2021. Available at:?https://www.ema.europa.eu/en/human-regulatory/overview/orphan-designation-overview.
- U.S. Food and Drug Administration (FDA). Priority Review. Available from:?https://www.fda.gov/patients/fast-track-breakthrough-therapy-accelerated-approval-priority-review/priority-review.
- The Non-Hodgkin?s Lymphoma Classification Project.?Blood.?1997;89:3909?3918.
- Anderson J., et al. Epidemiology of the non-Hodgkin?s lymphomas: distributions of the major subtypes differ by geographic locations. Non-Hodgkin?s Lymphoma Classification Project.?Ann Oncol.?1998;9(7):7;17?720.
- Wudhikarn, K., et al. Comparative effectiveness research in follicular lymphoma: current and future perspectives and challenges.?J Comp Eff Res.?2014.
- Data on File, Novartis, 2020.
- Schuster, S., et al. Chimeric antigen receptor T cells in refractory B-cell lymphomas.?NEJM.?2017;377(26):2545?2554.
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