Pierre Fabre aligns with FDA on twice-rejected T-cell therapy

Pierre Fabre says it has aligned with FDA on a potential path forward for resubmission of the company’s BLA for tabelecleucel, an allogeneic T-cell therapy with a proposed indication for relapsed/refractory Epstein-Barr virus positive post-transplant lymphoproliferative disease (EBV+ PTLD).

During the meeting, the FDA agreed that a single arm study using an appropriate historical control applicable to the trial population, conducted in a pre-specified manner, could serve as an adequate and well controlled study and provide safety and efficacy data in support of a marketing application of tabelecleucel for the proposed indication. As a part of the resubmission plan, Pierre Fabre will submit an updated dataset with additional patients and longer follow up from the pivotal phase 3 single arm ALLELE study of tabelecleucel in adults and children two years of age and older with R/R EBV+ PTLD following solid organ transplant or hematopoietic cell transplant as well as supportive data.

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. 

The agency had issued Pierre Fabre and partner Atara Biotherapeutics a CRL back in January, indicating it was unable to approve the tabelecleucel BLA in its present form. In what Atara called “a complete reversal of position by the FDA,” the CRL claimed that the single arm ALLELE trial (previously confirmed by the FDA as adequate to support the BLA filing) was no longer considered to be adequate to provide evidence of effectiveness for accelerated approval.

A year prior, the FDA had 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. The GMP compliance issues have been satisfactorily resolved.

Branded Ebvallo, tabelecleucel got the green light from the European Commission in December 2022. 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.