Atyr’s Covid-19 benefit claims raise questions

The group has blamed placebo “overperformance” on a high proportion of less-sick patients.

Trial Results

If Atyr Pharma had hoped for a big share price boost on the back of claims of activity in a study of its lead project, ATYR1923, in Covid-19 it will have been disappointed, as its stock opened up just 1% this morning. And quite right: scrutiny of the data, revealed after market close yesterday, raises doubts about whether the neuropilin-2 modulator conferred any real benefit.

The phase II study found a median time to recovery of 5.5 days in patients receiving 3mg/kg of ATYR1923 – just half a day shorter than that seen in placebo recipients. And a 1mg/kg cohort performed worse than placebo, with a median time to recovery of seven days. Atyr said the trial, in 32 hospitalised patients with severe respiratory complications but not receiving ventilation, had not been powered to show significance.

During a conference call yesterday Atyr’s chief executive, Sanjay Shukla, pointed to what he called an “overperformance” in the placebo arm of the trial. And, handily, he had a potential explanation for this: “nearly all” of the patients aged over 65 had been randomised to the treatment arms, while the ATYR1923 cohorts also included more patients with severe hypoxia or comorbidities at baseline.  

Overall, he said, this led to a sicker population in the treatment groups versus the placebo cohort, which might have skewed the results.

Another potential confounder is the fact that patients in the 1mg/kg arm received ATYR1923 later, after 5-6 days in hospital, versus 3-4 days in the 3mg/kg and placebo groups.

Sturdy?

While this looks like bad study planning at best, Mr Shukla termed the performance of the 3mg/kg arm “sturdy”, and noted that placebo patients in Atyr’s study did better than that has been seen historically with the likes of Gilead’s Veklury and Lilly’s baricitinib.

It is true that Veklury’s emergency use authorisation was based on a median time to recovery of 10 days, versus 15 days with placebo; meanwhile, baricitinib gained an EUA on the back of a study showing that, in combination with Veklury, it reduced the median time to recovery to seven days, versus eight with Veklury alone.

However, a key difference might have been dexamethasone, the only drug to show a clear mortality benefit in Covid-19 so far. The aforementioned trials did not include the steroid, while 30 of the 32 patients in Atyr’s trial were receiving dexamethasone as background therapy, according to Mr Shukla. Background Veklury was also allowed.

Still, the chief exec maintained that in other trials using dexamethasone background therapy patients tended to recover in 7-10 days.

Ideally, Atyr should carry out a larger trial to confirm its initial findings. Mr Shukla said the company was awaiting full results from the phase II study, as well as monitoring the evolving Covid-19 treatment landscape, before deciding on its next steps.

Given the current dire situation, one analyst suggested attempting to get an EUA on the back of the current study. Mr Shukla agreed that this could be on the cards, saying the group would have to have discussions with the US government.

However, just because the agency has given the nod to other therapies based on questionable evidence, it does not mean that ATYR1923 could – or should – get a quick green light.

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