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by Nick Paul Taylor

Apellis Pharmaceuticals’ pegcetacoplan has beaten Alexion’s blockbuster Soliris in a head-to-head phase 3 trial. The result suggests Apellis can challenge Alexion’s dominance in paroxysmal nocturnal hemoglobinuria (PNH), but the biotech needs to talk to the FDA before deciding on the next steps.

For the phase 3, investigators enrolled 80 PNH patients who were anemic despite taking Soliris and randomized then to receive either Alexion’s blockbuster or Apellis’ rival complement inhibitor. 

After 16 weeks, hemoglobin levels in the pegcetacoplan arm had increased by 3.8 g/dL over the Soliris group, resulting in the trial hitting its primary endpoint. The trial also hit some key secondary endpoints. Notably, 85% of patients on pegcetacoplan were transfusion-free at week 16, compared to 15% of their peers in the Soliris cohort. 

Analysts at Cantor Fitzgerald talked up the significance of data against both endpoints, noting that Apellis had outperformed expectations and delivered results that physicians will view as clinically meaningful.

“We think investors were looking for a hemoglobin increase of 2g/dL+ vs. Soliris,” the analysts wrote in a note to investors. “We think the benefit on transfusion independence is highly meaningful. Transfusions are a key endpoint of focus for physicians where our checks suggested a ~20% difference is seen as highly meaningful vs. this is a 70% difference.”

Those positives led investors to drive Apellis’ share price up by more than 50% shortly after the data dropped. However, enthusiasm had waned somewhat by the time the market opened, when Apellis’ shares traded up around 30% over the closing price yesterday.

Exactly why investors cooled on the data is unclear, but the information released by Apellis features potential areas of concern. Rates of injection site reaction, diarrhea and discontinuation were higher in the pegcetacoplan arm, and Apellis’ drug failed to show non-inferiority versus Soliris in terms of its effect on lactate dehydrogenase. 

There are also outstanding questions about when Apellis will be able to file for approval of the drug. Apellis set out the current situation in a regulatory filing.   

“The FDA has advised us that, for the approval of a new treatment for PNH, hemoglobin stabilization in conjunction with change in transfusion dependence constitute accepted clinical benefit, but that a rise in hemoglobin levels may not translate to clinical benefit in patients who entered the trial with high hemoglobin levels, such as permitted by the inclusion criteria of the PEGASUS trial, and who do not require transfusions,” the company wrote.

Apellis plans to meet with regulatory agencies in the coming months to discuss the next steps for the drug.