The European Medicines Agency’s Committee for Orphan Medicinal Products (COMP) is recommending orphan designation for a cytomegalovirus-specific cytotoxic T-lymphocyte product (CMV-CTLs) intended to treat CMV infection in patients with impaired cell-mediated immunity.
The CMV-CTLs are designed to find and kill cells expressing CMV.
To create CMV-CTLs, T cells are collected from the blood of third-party donors and then exposed to CMV antigens.
The resulting activated T cells are then expanded, characterized, and stored for future use in a partially HLA-matched patient.
The CMV-CTLs are being developed by Atara Biotherapeutics, Inc.
The cells are currently under investigation in a pair of phase 2 trials (NCT01646645 and NCT02136797).
Results of a phase 1 trial (published in Biology of Blood and Marrow Transplantation in 2015) suggested CMV-CTLs are safe and can clear CMV infection in patients who have undergone allogeneic hematopoietic stem cell transplant.
The trial included 17 transplant recipients with CMV viremia or clinical infection that persisted despite prolonged treatment with antiviral drugs. Fourteen of the patients had received T-cell-depleted transplants without graft-versus-host disease (GVHD) prophylaxis.
Sixteen of the patients received CMV-CTLs created using cells derived from their transplant donor, and 1 patient received cells from a third-party donor.
Fifteen patients achieved clearance of CMV viremia, including 3 of the 5 patients with overt disease and the patient who received cells from a third-party donor.
In addition, the researchers said CMV-CTLs were well-tolerated. None of the patients experienced fever, alterations in vital signs, or other toxicities during the first 48 hours of observation.
None of the patients developed manifestations of de novo acute GVHD, and GHVD did not worsen in either of the 2 patients who had GVHD prior to infusion.
About orphan designation
The COMP adopts an opinion on the granting of orphan drug designation, and that opinion is submitted to the European Commission for a final decision.
Orphan designation provides regulatory and financial incentives for companies to develop and market therapies that treat life-threatening or chronically debilitating conditions affecting no more than 5 in 10,000 people in the European Union, and where no satisfactory treatment is available.
Orphan designation provides a 10-year period of marketing exclusivity if the drug receives regulatory approval.
The designation also provides incentives for companies seeking protocol assistance from the European Medicines Agency during the product development phase and direct access to the centralized authorization procedure.
