Global ELARA trial demonstrated clinically meaningful benefit in patients with relapsed or refractory (r/r) follicular lymphoma (FL) as measured by complete response rate
Kymriah previously received FDA Regenerative Medicine Advanced Therapy (RMAT) designation in r/r FL based on preliminary ELARA trial findings, reflecting the unmet need for additional treatment options for this cancer type
ELARA trial findings will be included in regulatory submissions, with filing in the US anticipated in 2021, and the EU following. Results will be presented at an upcoming medical meeting
Interim analysis comes alongside milestones of 3,000th batch of CAR-T cells manufactured for patients worldwide and approval for commercial manufacturing at two additional sites in Europe
Basel, August 4, 2020 - Novartis today announced positive results from the Phase II ELARA trial of Kymriah (tisagenlecleucel) in patients with relapsed or refractory (r/r) follicular lymphoma (FL). At the interim analysis, the global study met its primary endpoint of complete response rate (CRR), as assessed by independent review committee. CRR is a standard measure of patient response to therapy in FL. No new Kymriah safety signals were observed. Results from the ELARA trial will be presented at an upcoming medical meeting and included in US and EU regulatory submissions.
Kymriah was the first-ever FDA-approved CAR-T cell therapy, and the first-ever CAR-T to be approved in two distinct indications. It is a one-time treatment designed to empower patients’ immune systems to fight their cancer. Kymriah is currently approved for the treatment of r/r pediatric and young adult (up to 25 years of age) acute lymphoblastic leukemia (ALL), and r/r adult diffuse large B-cell lymphoma (DLBCL)1.
"We are pleased that Kymriah is showing meaningful results and may provide a potentially definitive treatment option for patients with relapsed and refractory follicular lymphoma," said John Tsai, MD, Head of Global Drug Development and Chief Medical Officer, Novartis. "These results further support our efforts to reimagine medicine in this incurable malignancy and reach this underserved patient population, who are historically burdened with several years of various treatments."
Kymriah was developed in collaboration with the Perelman School of Medicine at the University of Pennsylvania, a strategic alliance between industry and academia, which was first-of-its-kind in CAR-T research and development.
Kymriah is currently approved for use in at least one indication in more than 25 countries and at more than 250 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. As Novartis prepares for the launch of a potential third indication for Kymriah, manufacturing capacity continues to ramp up. The Novartis global CAR-T manufacturing footprint spans seven facilities total, across four continents. This comprehensive, integrated footprint strengthens the flexibility, resilience and sustainability of the manufacturing and supply chain. With recent approvals from the European Medicines Agency (EMA), commercial manufacturing of Kymriah is now ongoing at the Novartis-owned facilities in Stein, Switzerland and Les Ulis, France, joining the Novartis-owned facility in Morris Plains, New Jersey, USA.
About Follicular Lymphoma
Follicular lymphoma, the second most common form of non-Hodgkin lymphoma (NHL), is an indolent lymphoma, and represents approximately 22% of NHL cases2,3. Despite new treatments that improve overall survival, FL is regarded as an incurable malignancy with a relapsing and remitting pattern4,5. Throughout the lifetime of a patient with relapsing FL, they may be exposed to a median of five lines of prior treatment, with an upper range of 12 lines6,7. Although patients in third or later line treatment for FL have multiple systemic therapies available, the efficacy of these regimens drops off rapidly in later lines5. Additionally, because of this relapsing and remitting pattern, patients who are refractory to treatment or quickly relapse may exhaust available treatment options5.
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. This international trial has enrolled patients from over 30 sites in 12 countries worldwide.
In Q2 2020, the FDA granted Regenerative Medicine Advanced Therapy (RMAT) designation to Kymriah in r/r FL, based on preliminary results from the ELARA trial. RMAT designation is intended to expedite the development and review of Kymriah as a regenerative therapy for this underserved patient population.
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 (tisagenlecleucel) US Important Safety information
Kymriah may cause side effects that are severe or life-threatening, such as Cytokine Release Syndrome (CRS) or Neurological Toxicities. Patients with CRS may experience symptoms including difficulty breathing, fever (100.4°F/38°C or higher), chills/shaking chills, severe nausea, vomiting and diarrhea, severe muscle or joint pain, very low blood pressure, or dizziness/lightheadedness. Patients may be admitted to the hospital for CRS and treated with other medications.
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. Patients should be advised to call their healthcare provider or get emergency help right away if they experience any of these signs and symptoms of CRS or neurological toxicities.
Because of the risk of CRS and neurological toxicities, Kymriah is only available through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called Kymriah REMS.
Serious allergic reactions, including anaphylaxis, may occur after Kymriah infusion. Kymriah can increase the risk of life-threatening infections that may lead to death. Patients should be advised to tell their healthcare provider right away if they develop fever, chills, or any signs or symptoms of an infection.
Patients may experience prolonged low blood cell counts (cytopenia), where one or more types of blood cells (red blood cells, white blood cells, or platelets) are decreased. The patient’s healthcare provider will do blood tests to check all of their blood cell counts after treatment with Kymriah. Patients should be advised to tell their healthcare provider right away if they get a fever, are feeling tired, or have bruising or bleeding.
Patients may experience hypogammaglobulinemia, a condition in which the level of immunoglobulins (antibodies) in the blood is low and the risk of infection is increased. It is expected that patients may develop hypogammaglobulinemia with Kymriah, and may need to receive immunoglobulin replacement for an indefinite amount of time following treatment with Kymriah. Patients should tell their healthcare provider about their treatment with Kymriah before receiving a live virus vaccine.
After treatment with Kymriah, patients will be monitored lifelong by their healthcare provider, as they may develop secondary cancers or recurrence of their cancer.
Patients should not drive, operate heavy machinery, or do other dangerous activities for eight weeks after receiving Kymriah because the treatment can cause temporary memory and coordination problems, including sleepiness, confusion, weakness, dizziness, and seizures.
Some of the most common side effects of Kymriah are difficulty breathing, fever (100.4°F/38°C or higher), chills/shaking chills, confusion, severe nausea, vomiting and diarrhea, severe muscle or joint pain, very low blood pressure, dizziness/lightheadedness, and headache. However, these are not all of the possible side effects of Kymriah. Patients should talk to their healthcare provider for medical advice about side effects.
Prior to a female patient starting treatment with Kymriah, their healthcare provider may do a pregnancy test. There is no information available for Kymriah use in pregnant or breast-feeding women. Therefore, Kymriah is not recommended for women who are pregnant or breast feeding. Patients should talk to their healthcare provider about birth control and pregnancy.
Patients should tell their healthcare provider about all the medicines they take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.
After receiving Kymriah, patients should be advised that some commercial HIV tests may cause a false-positive test result. Patients should also be advised not to donate blood, organs, or tissues and cells for transplantation after receiving Kymriah.
Please see the full Prescribing Information for Kymriah, including Boxed WARNING, and Medication Guide at www.Kymriah.com