Apellis will appeal CHMP’s rejection of pegcetacoplan

Apellis Pharma has said it will seek a re-evaluation of its marketing application for Syfovre for eye disease geographic atrophy (GA) after the EMA’s human medicines committee turned it down for a second time.

The CHMP said at its late June meeting that it was issuing a negative opinion for Syfovre (pegcetacoplan) for the treatment of GA secondary to age-related macular degeneration (AMD), a progressive disease leading to sight loss.

The panel maintained that, while clinical data for the complement C3 inhibitor did show a slowing in the growth of GA lesions in these, that did not translate into a “clinically meaningful” benefit for patients.

It also asserted that the injections into the eye “carry a significant risk of adverse events, including the development of other forms of AMD or inflammation in the eye, that could further worsen vision.” Last year, there were reports of several cases of retinal vasculitis with the drug, prompting an investigation by the company.

The same conclusion on efficacy and safety was reached at an earlier CHMP meeting in January, which also prompted an appeal, although, a legal decision by the Court of Justice of the European Union (CJEU) on the composition of EMA expert groups led to a reset of the review for Syfovre.

Apellis has said it will seek a re-examination of the CHMP’s opinion, noting that there were “multiple dissenting voices” by members of the panel. It also said that specialists at an ad hoc expert group meeting agreed that the size of GA lesion is an acceptable primary outcome measure for a trial in GA.

The situation in the EU for Syfovre is different to the US, where the FDA gave Syfovre the go-ahead for GA secondary to AMD in February 2023, the first drug to be approved for the condition. Apellis said it hopes to get a verdict from the latest appeal in the EU by the end of the year.

Pegcetacoplan is approved in a subcutaneous form as Empaveli/Aspaveli for the rare blood disorder paroxysmal nocturnal haemoglobinuria (PNH). It was also being developed for neurodegenerative disorder amyotrophic lateral sclerosis (ALS), but that programme was dropped after the drug failed a phase 2 trial last year.

Analysts have previously suggested that Syfovre could eventually become a multi-billion-dollar blockbuster, with Jefferies estimating peak sales of $6 billion before the setbacks with the drug.

Apellis reported sales of $138 million with Syfovre in the first quarter of this year, with another $26 million contributed by Empaveli/Aspaveli in PNH. The systemic form of pegcetacoplan is also being developed for C3 glomerulopathy (C3G) and immune complex glomerulonephritis (IC-MPGN), with results due later this year.