First Allogenic CAR-T Treatment One Step Closer to Market Authorisation
The first allogenic CAR-T therapy in the world is one step closer to approval. Ebvallo (Tabelecleucel) is an allogenic t-cell therapy for Epstein-Barr virus positive post-transplant lymphoproliferative disease . PTLD arises as a complication of organ and stem cell transplants .
PTLD is defined by the overproduction and spread of lymphocytes (white blood cells) . The lymphocytes that continue to grow may be infected with the Epstein-Barr virus after an organ transplant. Epstein-Barr is a common virus and most commonly associated as the cause of infectious mononucleosis . Most infections of Epstein-Barr are undetected, and complications are rare. However, organ transplant patients undergo immunosuppression therapies, increasing the risk of developing infections.
Atara’s treatment is the first CAR-T therapy for this type of lymphoma. On October 13th 2022, the Committee for Medicinal Products for Human Use recommended to grant market authorisation for Ebvallo . Atara was not able to provide comprehensive data for the efficacy and safety of Ebvallo, as such the recommendation was for authorisation under exceptional circumstances. Atata’s therapy has also received breakthrough designation by both the EMA and FDA. It was granted PRIME designation in the EMA, as well as breakthrough drug status by the FDA . Atara expects the EMA to provide formal market authorisation by the end of 2022.
Atara is conducting multiple clinical trials with Ebvallo, one of which has entered Phase III. The ALLELE study is being conducted to determine the benefit and safety of Ebvallo for patients with an organ transplant after treatment with rituximab, treatment with rituximab and chemotherapy, or allogeneic hematopoietic cell transplant .
Commercial autologous CAR-T treatments have been approved for specific indications within Europe, Canada, and the United States, these treatments require T-cells from each individual patient. Allogeneic therapies allow for collection of T-cells from a donor, not specifically from the patient. These therapies have also been referred to as “off the shelf” since one donor can provide the cellular material to treat several patients.
A key advantage for allogenic therapies is centralisation. The manufacturing of CAR-T cells can be conducted at a large scale and distributed to required patients. With current autologous CAR-T treatments, this scale is not feasible as each patients’ cells are harvested for their specific treatment. A more centralised approach can reduce manufacturing costs, therefore potentially reducing the overall price of the therapy. Yet, tere are also numerous challenges associated with allogeneic gene therapies. One major obstacle is graft versus host disease, when the donated T-cells begin to attack the patient’s own cells .
The importance of cell and gene therapies have certainly caught the attention of researchers, industry, and regulators. Perhaps most importantly, cell and gene therapies can provide patients with new treatment options. For patients with PTLD, it is now one step closer.
In the Social Pharmaceutical Innovation (SPIN) consortium, CAR-T cell manufacturing is a central case study of alternative production and manufacturing across our national contexts. As such, we look forward to following this innovation closely as it is predicted to have a significant impact on the treatment of patients with rare diseases.
1. Atara Bio. Tabelecleucel (tab‐cel) – Investigational PTLD T-cell immunotherapy. 2022; Available from: https://www.atarabio.com/pipeline/tabelecleucel/.
2. National Organization for Rare Disorders. Post-Transplant Lymphoproliferative Disease. 2018; Available from: https://rarediseases.org/rare-diseases/posttransplant-lymphoproliferative-disorders/.
3. Tosh, P.K. Mononucleosis and Epstein-Barr: What's the connection? 2020; Available from: https://www.mayoclinic.org/diseases-conditions/mononucleosis/expert-answers/mononucleosis/faq-20058444.
4. European Medicines Agency, Summary of opinion (initial authorisation) Ebvallo (tabelecleucel). 2022.
5. Atara Biotherapeutics, Tabelecleucel for Solid Organ or Allogeneic Hematopoietic Cell Transplant Participants With Epstein-Barr Virus-Associated Post-Transplant Lymphoproliferative Disease (EBV+ PTLD) After Failure of Rituximab or Rituximab and Chemotherapy (ALLELE). 2017-2027, ClinicalTrials.gov.
6. Kim, D.W. and J.-Y. Cho, Recent Advances in Allogeneic CAR-T Cells. Biomolecules, 2020. 10(2): p. 263.
Photo by Adrien Converse on Unsplash
Written by: Faisal Ali Mohamed (PhD Student)