Ebvallo gets a second US knockback

Atara believed that it had sorted out the third-party manufacturing issues that led to an FDA complete response letter for its T-cell therapy Ebvallo a year ago – but the group has now been scuppered by what, it says, is a new problem.

On the first day of the JP Morgan meeting the company disclosed a second CRL – the latest in a long line of calamities. And this one could be fatal for the project, given that it raises questions about the single-arm Allele trial used as the basis for the filing. With cash-strapped Atara depending on a milestone payment from its partner Pierre Fabre, the biotech’s future looks grim.

Atara’s stock fell 53% on Monday.

Pierre Fabre, which now has responsibility for Ebvallo, had been seeking accelerated approval in relapsed/refractory Epstein Barr virus-positive post-transplant lymphoproliferative disease, based on the uncontrolled Allele study, with a PDUFA date of 10 January.

Crucially, the study, which Atara said “was previously confirmed by the FDA as adequate to support the BLA filing”, has now been deemed insufficient. Furthermore, the FDA said the trial’s interpretability is confounded by study design, conduct and analysis. The agency has requested a new study, Pierre Fabre noted.

The companies added that the original manufacturing problems had been resolved, and that no safety issues had been raised.

Of course, this is Atara and Pierre Fabre’s take on the matter – until the CRL is published, the FDA’s standpoint will remain unknown. Investors could get a clearer picture shortly, with the agency recently publishing a raft of rejections, and promising to make these available promptly in future.

If what Atara and Pierre Fabre say is accurate, this could be bad news not just for those companies, but also for other rare disease developers. Pierre Fabre said it received the CRL on Friday, but it was made public a day after the FDA announced that it was increasing flexibility on requirements for cell and gene therapies – although this largely concerned chemistry, manufacturing and control issues.

Dwindling milestone

Pierre Fabre plans to request a meeting with the FDA, and the partners still hope to find a path forward for Ebvallo, Atara said.

However, time is running out for the smaller group, which had just $8.5m in the bank at the end of 2025.

Atara had been awaiting a milestone from Pierre Fabre, due on Ebvallo’s approval, but the value of this has been dwindling. It was once set to total $60m, then was reduced to $40m last year as Pierre Fabre took on manufacturing and remediation at the affected facility.

Now Atara has disclosed that the milestone has shrunk again, to $31m, “in exchange for the right to receive an additional $15m potential milestone payment upon achieving a certain commercial milestone”.

Whatever the amount, this payment now looks in doubt – leaving things looking very uncertain for Atara.