Tabelecleucel, tab‐cel® is an off-the-shelf, allogeneic T-cell immunotherapy in Phase 3 studies for patients with EBV+ PTLD (Epstein-Barr virus associated post-transplant lymphoproliferative disease). Additional studies are focusing on EBV-associated hematologic and solid tumors, including nasopharyngeal carcinoma (NPC) and chronic active EBV. PTLD is a type of cancer or lymphoma that may occur after bone marrow or organ transplant.
In February 2015, the FDA granted tabelecleucel Breakthrough Therapy Designation for Epstein-Barr virus associated post-transplant lymphoproliferative disorder following allogeneic hematopoietic cell transplant (HCT), and in October 2016, tabelecleucel was accepted into the EMA Priority Medicines (PRIME) regulatory pathway for the same indication, providing enhanced regulatory support. In addition, tab‐cel® has orphan status in the U.S. and EU.
Tab-cel® is in Phase 3 clinical development for the treatment of EBV+ PTLD following an allogeneic hematopoietic cell transplant or solid organ transplant (ALLELE study), and Atara recently initiated a Phase 1/2 study in NPC. Tab-cel® is also available to eligible patients with Epstein-Barr virus-associated diseases and malignancies for whom there are no other appropriate therapeutic options through an expanded access program.
Post-transplant lymphoproliferative disease (PTLD) is a type of cancer or lymphoma that may occur after bone marrow or organ transplant.
A patient who receives a transplant must take medications to suppress their immune system (immunosuppression) so that their body will not reject the new bone marrow or organ. When the immune system is suppressed, it is easier to become sick. Sometimes when a transplant patient is infected with Epstein-Barr virus (EBV), the virus may cause a serious cancer of the blood known as PTLD.
EBV is a common virus that infects over 90% of people in the world. For most healthy individuals, it causes common cold like symptoms and then stays in the body but is usually controlled by the immune system, so there are no further symptoms after the initial infection. If a person has a suppressed immune system, the EBV can become reactivated and cause an uncontrolled growth of cells in the patient’s lymph nodes and other organs. When abnormal cells multiply out of control, it may result in cancer.
PTLD is a common cancer of the blood after transplant but is still considered a rare disease that only occurs in a small percentage of transplant patients. Rates of PTLD cancer are higher for people who have bone marrow and organ transplants that require higher levels of immunosuppression.
In immunocompromised patients, such as those undergoing allogeneic hematopoietic cell transplants (HCT) or solid organ transplants (SOT), Epstein-Barr virus associated post-transplant lymphoproliferative disorder (EBV+ PTLD), represents a life-threatening condition.
(1) Expected median survival for patients with EBV+ PTLD following HCT who have failed rituximab first line therapy is 16 to 56 days; Atara estimated 1-year survival based on analysis of Ocheni S, et al. EBV reactivation and post transplant lymphoproliferative disorders following allogeneic SCT. Bone Marrow Transplantation. 2008 Aug;42(3):181-6; Fox CP, et al. EBV-associated post-transplant lymphoproliferative disorder following in vivo T-cell-depleted allogeneic transplantation: Clinical features, viral load correlates and prognostic factors in the rituximab era. Bone Marrow Transplant. 2014;49(2):280-6.
|Indication||Preclinical||Phase 1||Phase 2||Phase 3|
|RR EBV+ PTLD following HCT|
|RR EBV+ PTLD following SOT|
|Nasopharyngeal carcinoma (NPC)|
|RR EBV+ PTLD following HCT||Phase 3|
|RR EBV+ PTLD following SOT||Phase 3|
|Nasopharyngeal carcinoma (NPC)||Phase 2|
|EBV+ cancers||Phase 1|