Ebvallo’s US soap opera plays on

The Ebvallo soap opera has entered the stage where investors try to decipher the semantics of a press release to gauge what’s changed between the drug’s second complete response letter in January and now, following Pierre Fabre’s meeting with the FDA.

According to Pierre Fabre, Ebvallo’s licensee, the FDA has agreed that an uncontrolled study using a historical control “could serve in support of a marketing application” for Ebvallo. At issue now is whether longer-term data from Allele – the uncontrolled study at the heart of two Ebvallo CRLs – could fulfil this purpose, and whether that alone would be enough for the FDA.

Such a scenario would represent a significant U-turn at the agency, which just five months ago slammed Allele not only for being uncontrolled, but also for having deficiencies in design, conduct and analysis, for including an unplanned efficacy analysis, and for its high attrition rate and treatment interventions that confounded the interpretability of its data.

That stance emerged after Ebvallo’s originator, Atara, had earlier claimed that the FDA said the uncontrolled Allele trial would be adequate to support a filing. According to Pierre Fabre, to which the cash-strapped Atara licensed Ebvallo’s US rights in 2023, the FDA’s view by January had changed to one where the agency was demanding that a new study be run.

Pierre Fabre is seeking accelerated approval for Ebvallo, a donor-derived T-cell therapy against EBV antigens, in relapsed/refractory Epstein Barr virus-positive post-transplant lymphoproliferative disease.

Politics and Prasad

There is a political dimension to this, and that concerns Vinay Prasad, a known critic of some cell therapies who was director of the FDA’s Center for Biologics Evaluation and Research at the time of the second CRL. Prasad left the agency last month, and – the bulls will hope – with him out of the picture the opposition to Ebvallo will be gone too.

That remains to be tested, though with Atara closing up 92% on Thursday investors clearly have high hopes. In a note to clients Mizuho’s Salim Sayed wrote that the “FDA has agreed that the design of Allele would be adequate for resubmission (ie, no new trial necessary)”, though this isn’t quite what Pierre Fabre’s statement says.

Rather, the group says the FDA favours a “single-arm study using an appropriate historical control” – a description that may or may not apply to Allele. As the FDA disclosed when it published the Ebvallo CRL, Allele’s choice of external control was based on historical estimates and a null hypothesis for ORR of 20%, “which was not supported by reference to a specific control population”.

The Replimune angle

Those hoping that the FDA is about to perform a U-turn will be mindful of the experience of another company, Replimune, whose oncolytic virus vusolimogene oderparepvec received its own second CRL last month. This concerned similar issues to Ebvallo’s, with a dispute over the acceptability of an uncontrolled trial, but seems to have been driven by a different FDA division.

However this plays out, the investment case for Atara is now a guessing game as to the timing of milestones and payouts, against a dwindling cash balance that totalled just $8.5m at the end of 2025.

Atara has a market cap of $85m, and recently managed to defer an imminent $9m payout under a royalty deal, from 30 June 2026 to 1 January 2028. It is due a milestone from Pierre Fabre on Ebvallo’s US approval, thought to stand at $31m. The next regulatory update is expected in the third quarter.

An Ebvallo timeline

Source: OncologyPipeline & company updates.