Groundbreaking Drug Launches
Tabelecleucel (Ebvallo)
Mechanism of Action: Immunologic cytotoxicity; T lymphocyte replacements Drug class: T lymphocyte cell therapies Originator: Memorial Sloan-Kettering Cancer Center Developer: Atara Biotherapeutics Indication: Lymphoproliferative disorders Launched: UK, Austria, Germany
Awaiting approval: USA Trials: ALLELE
Lymphoproliferative disorders
Lymphoproliferative disorders (LPDs) refer to a broad category of conditions that involve an abnormal proliferation of a type of white blood cell. Some of these disorders impact the immune system, while others are classified as blood cancers. Common symptoms include swollen lymph nodes, an enlarged liver and spleen, fatigue, fever, and unexplained weight loss.
Prevalence
The prevalence of lymphoproliferative disorders (LPDs) varies depending on the specific type of disorder and the population being studied. • Chronic Lymphoproliferative Disorders (CLPDs): The annual incidence of CLPDs is approximately 10 per 100,000 people. CLPDs are a group of conditions characterized by the excessive production of lymphocytes in the body. • Post-transplant Lymphoproliferative Disorders (PTLDs): The incidence of PTLDs is 2.39 per 1,000 person-years. PTLDs are the most common type of malignancy observed in individuals who have undergone organ transplantation. • EBV-associated Lymphoproliferative Disorders: The median age of individuals with EBV-associated LPDs is 75 years.
Treatment challenges
Treating lymphoproliferative disorders (LPDs) presents several challenges due to the disease's heterogeneity, the risk of infection, and the need to carefully balance treatment with the possibility of graft failure. Challenges: • Risk of Infection: Patients with LPDs are often immunosuppressed, which increases their vulnerability to infections. • Graft Failure: Chemotherapy can lead to graft failure, particularly in individuals who have undergone hematopoietic stem cell transplantation (HSCT). • Graft-versus-host Disease (GVHD): Reducing immunosuppression to treat post-transplant lymphoproliferative disorders (PTLD) can elevate the risk of GVHD. • Heterogeneity: LPDs encompass a wide range of types, with symptoms that can vary significantly from one patient to another. • Treatment Options: There is no universally accepted treatment for LPDs, and some therapies are only available under specific circumstances.
Why is Tabelecleucel poised to make an impact in 2025?
Tabelecleucel will be the first therapy approved in the U.S. for Epstein-Barr virus-positive post-transplant lymphoproliferative disease (EBV+ PTLD), potentially opening a new revenue stream for Atara Biotherapeutics. Atara could receive an additional $60 million milestone payment from Pierre Fabre, contingent on FDA approval of the tab-cel BLA, as well as significant double-digit tiered royalties based on net sales and milestones tied to the commercial success of tab-cel. The company remains focused on maximizing this potential future value for all shareholders. Atara has also entered into a non-binding term sheet with Redmile Group for up to $15 million in funding through an equity line of credit, which the company believes will be sufficient to support the activities needed to achieve BLA approval. Additionally, Atara is exploring other financing options, including non-dilutive sources of capital.
The US FDA accepted its BLA based on promising results from the ALLELE trial and set a PDUFA date of January 15, 2025. However, in January, the US FDA issued a Complete Response Letter (CRL) citing GMP compliance issues, which led to a clinical hold for EBVALLO. Recently, Atara announced plans to address the FDA’s concerns and lift the clinical hold to support a BLA resubmission.
Regulatory milestones
Registrational Trial
Atara Biotherapeutics received a Complete Response Letter (CRL) from the FDA for the EBVALLO™ (tabelecleucel) Biologics License Application as a monotherapy for EBV+ PTLD in patients aged two and older who have had prior therapy, based on the ALLELE trial results.
ALLELE:
A multicenter, open-label, phase 3 study to assess the efficacy and safety of tabelecleucel for the treatment of EBV+ PTLD in the setting of SOT-R and SOT-R+C (Cohort [C]-SOT) or HCT after failure of rituximab (C-HCT) (NCT03394365).
“Tabelecleucel demonstrated 50.7% efficacy in relapsed EBV-positive PTLD with a 23-month median response, offering durable outcomes for patients with limited options”