Atara T-cell immunotherapy hit with surprise CRL

The U.S. FDA has issued a complete response letter (CRL) for Atara Biotherapeutics’ Ebvallo (tabelecleucel) as monotherapy treatment for adult and pediatric patients two years of age and older with Epstein-Barr virus positive post-transplant lymphoproliferative disease (EBV+ PTLD), who have received at least one prior therapy including an anti-CD20 containing regimen.

The CRL indicates that the FDA is unable to approve the Ebvallo BLA in its present form. This is the second CRL Atara has received for Ebvallo. A year ago, the FDA rejected Atara’s BLA solely due to GMP compliance issues at a third-party manufacturing facility. At the time, the agency did not raise any concerns with respect to the safety, efficacy or trial design.

Now — while the agency confirmed that the GMP compliance issues have been satisfactorily resolved — in what Atara is calling “a complete reversal of position by the FDA,” the latest CRL claims that the single arm ALLELE trial (previously confirmed by the FDA as adequate to support the BLA filing) is no longer considered to be adequate to provide evidence of effectiveness for accelerated approval.

According to Atara, “The FDA’s new position is contrary to the FDA’s prior guidance to Atara, the FDA’s alignment with Atara on the clinical trial data set, and the acceptance of the trial design as a single arm study as relevant for this patient population at BLA submission. This prior alignment had been reached by Atara and the FDA through multiple, documented meetings held over the past five plus years.”

Atara, together with partner Pierre Fabre Laboratories, plan to urgently interact with the FDA to find a path forward for the timely accelerated approval of Ebvallo.

Ebvallo, which got the green light from the European Commission in December 2022, is an allogeneic, EBV-specific T-cell immunotherapy designed to target and eliminate EBV-infected cells. EBV+ PTLD is a rare, acute and potentially deadly hematologic malignancy that occurs after transplantation when a patient's T-cell activity is compromised by immunosuppression. Atara is developing the therapy globally with Pierre Fabre Laboratories, through a deal that was expanded in December 2023. Per the deal, Atara is set up to receive a $60 million milestone payment from Pierre Fabre following FDA approval of the Ebvallo BLA.