Updated: Apellis says eye inflammation ‘very rare’ among patients taking Syfovre, but questions remain on safety

Apellis Pharmaceuticals still can’t pinpoint exactly what’s behind the rare cases of eye inflammation that’s been reported in patients taking its geographic atrophy drug Syfovre. And despite execs’ pledge to be transparent, the lack of answers is scaring investors.

Both the American Society of Retina Specialists’ Research and Safety in Therapeutics Committee (ASRS ReST committee) — which first flagged the safety concerns — and Apellis issued updates over the weekend on their respective reviews, with slight discrepancies. The ASRS ReST committee confirmed the discovery of two more cases of retinal vasculitis in the past two weeks, bringing the total number of cases to eight; meanwhile, by Apellis’ count, there have been seven confirmed cases of occlusive/non-occlusive retinal vasculitis since Syfovre’s launch in March.

In Apellis’ second quarter earnings call, which immediately pivoted to Syfovre, execs vowed to handle the situation “with the utmost integrity and transparency.” But they also conceded that much remains unknown.

“We do not know the cause yet. And realistically, we may never identify a singular cause,” Apellis CEO Cedric Francois said. “What we do know, however, is that these events have been very rare and sporadic, and that zero events were reported in our clinical studies.”

He added later that so far, the company has only been able to rule out drug product and manufacturing, and the rest remains to be researched.

Caroline Baumal

Apellis shares $APLS, which took a big 65% plunge and had billions in market cap wiped out in wake of the safety warning in mid-July, were up almost 14% to $36.5 in pre-market trading — before dropping to $25.9 after the bell.

Retinal vasculitis is a “severe inflammatory event that can potentially lead to significant vision loss,” according to CMO Caroline Baumal.

Of the seven cases confirmed by Apellis, two have recovered their vision “nearly back to baseline,” she said on the call. Two more have severe vision loss that she said is not likely to resolve — and the other three confirmed cases are evolving.

Safety reviews 

Syfovre won FDA approval in February. So far, Apellis has distributed 68,000 commercial vials — with an estimate of 60,000 administered to patients — and given 23,000 injections in clinical trials.

There were intraocular inflammation cases in those trials; when the retinal vasculitis reports first appeared, Apellis said, it looked back at those cases. Both internal and external experts confirmed none were vasculitis events.

Following the drug’s launch in March, Apellis said, there were two events following injections in April, two in May and three in June.

Baumal acknowledged that Apellis’ and ASRS’ reported numbers of vasculitis events are slightly different because they make determinations independently, and the complexity of the cases makes it difficult to interpret.

“However, we are working closely with ASRS to make sure we are better aligned in how we evaluate each of these events going forward,” she said.

The ReST committee presented its latest findings on the cases of retinal vasculitis during the ASRS annual scientific meeting, providing “a LOT of details on each individual patient,” per a note from Evercore ISI analyst Umer Raffat, who attended the session.

“While the discovery of new cases is disappointing, we believe it is a smaller number of cases than many investors had feared,” TD Cowen analysts wrote. “Nonetheless, many questions remain about the etiology, per patient incidence, and ways to mitigate the risk.

Discussions around the safety concerns overshadowed the company’s presentation of long-term results at the meeting. After 30 months of follow-up, patients taking Syfovre continued to see reduced geographic atrophy lesion growth compared to the projected sham arm.

Apellis may soon have a competitor in Iveric Bio, whose geographic atrophy drug is due for an FDA decision in mid-August.

“For now, we expect retinal specialists will still view both products as similar in efficacy, as noted multiple times over the course of the last several months as well as at OIS, and continue to assess risk/benefit based on patient severity,” Stifel analysts wrote in a note.

On the earnings call, Francois admitted the safety events may impact sales trajectory in the near-term, but added, “we don’t know the magnitude.”

The company said on the call it would provide quarterly updates on the rates of retinal vasculitis moving forward — but not necessarily on the investigation into the cause.

“We’re not going to make an update unless we have real clarity around understanding this,” Francois said.

Editor’s note: This story has been updated to add comments from Apellis executives during the company’s second quarter earnings call and reflect the latest changes in stock price.

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