Apellis Pharmaceuticals and a major medical organization over the weekend revealed new details about rare, but potentially serious, side effects that have cast a shadow over the biotechnology company’s newly launched drug for a common type of vision loss.
On Saturday, Apellis said that, since the February U.S. approval of its drug Syfovre in geographic atrophy, seven instances of a type of eye inflammation called retinal vasculitis have been confirmed by its internal safety committee and outside retinal specialists. Four were classified as “occlusive,” a possibly blinding condition in which blood flow to the retina is blocked.
Two cases of retinal vasculitis occurred in April, two in May and three in June, according to Apellis. The company is also evaluating, but hasn’t yet confirmed, one additional reported case.
In the company’s statement, CEO Cedric Francois said there is “no indication that drug product or manufacturing issues” are to blame for the side effects, which he described as “very rare.” Apellis didn’t observe those side effects across the 23,000 injections given to patients in clinical testing. By July 29, more than 68,000 vials of the drug had been distributed to physician practices, it said.
“The safety of patients has always been — and continues to be — our top priority at Apellis,” Francois said in a statement. “We will continue to collaborate with the retina community to deliver a safe, effective treatment for [geographic atrophy].”
Apellis’ figures differ slightly from those compiled so far by a safety committee advising the American Society of Retinal Specialists, which flagged the side effects to doctors earlier this month. Slides presented at the organization’s yearly meeting this weekend showed seven confirmed instances of occlusive retinal vasculitis, and another “suspected” case currently being reviewed. The cases occurred within 15 days of an injection, among patients between 60 and 96 years old. Their cause remains unclear.
The group previously urged “vigilance and reporting of any adverse treatment related events,” as well as “close follow up” after administration of Syfovre. Stat News recently reported that a doctor running ASRS’ safety committee has financial ties to rival drugmaker Iveric Bio.
On a conference call with analysts on Monday, Francois said that, within a broader investigation, the company is examining whether the drug’s mechanism — blocking a part of the immune system known as the complement system — is causing the problem. That’s still unclear, as is whether retinal vasculitis is more likely to occur after a patient's first injection or later on.
“We just don’t know a lot yet, other than the fact that it’s an extremely rare event that is sporadic in nature,” Francois said.
The frequency of the side effects could have significant implications for Apellis and use of Syfovre. Shares of the company soared to highs in the months following Food and Drug Administration approval of Syfovre. The drug is the first marketed treatment for geographic atrophy, a disease estimated to affect 1 million people in the U.S. alone.
Apellis claims its drug can slow the disease’s progression, as well as the growth of its hallmark patchy eye lesions. Early sales outpaced the expectations of Wall Street analysts, surging from $18 million in the first three months of the year to about $67 million in the second quarter, Apellis said Monday.
Some analysts forecast the drug will eventually earn more than $3 billion in peak yearly sales.
Safety has been a concern before. The risk of side effects that were observed in testing, such as inflammation and the formation of new blood vessels in the eye, may grow with time. And though new data show the drug’s effects on eye lesions may also increase as patients receive more injections, Apellis hasn’t yet proven Syfovre can slow vision loss.
The retinal vasculitis cases in commercial use adds a new factor to doctors’ and patients’ risk-benefit calculations. Apellis shares have lost nearly two-thirds of their value since the ASRS disclosed them. Some analysts have drawn comparisons to Beovu, a Novartis drug for a different type of vision loss. Use of Beovu has been limited due to warnings about side effects.
With Beovu, retinal vasculitis was eventually determined to occur at a rate of about 14 per 10,000 injections, Evercore ISI analysts Umer Raffat and Jon Miller recently wrote.
In the case of Apellis, investors were reportedly fearing more than 20 cases of occlusive retinal vasculitis would be disclosed in Apellis’ update. Instead, rates are tracking closer to about 1 per 10,000, Raffat and Miller wrote in a note over the weekend.
Apellis executives took steps to distance the company’s drug from Beovu, noting that retinal vasculitis was observed in clinical testing of Novartis’ medicine, but not in studies of Syfovre. The “onset and clinical features” of the side effects are also different, said Chief Medical Officer Caroline Baumal.
Still, an informal survey Apellis conducted after the ASRS sent its letter indicates that usage may change going forward. One-third of the 41 retinal specialists surveyed said they’d stop administering Syfovre until more information is available, while another third said they’d only give the drug to previously treated patients. The remainder will continue administering the drug on new and treated patients, as they had before.
"While the launch has been nothing short of spectacular, these events will clip its wings but, in our view, not wipe out its opportunity," wrote Stifel analyst Annabel Samimy, in a note to clients.
Apellis shares fell another 15% to less than $30 apiece on Monday, levels the company hasn’t seen since 2020. They were worth more than $85 per share in early July.
Editor’s note: This story has been updated with commentary from a conference call.