Days after FDA clears C3 drug, Apellis spotlights ex-US PhIII win among patients who haven't taken Soliris
Throughout Apellis’ development program for pegcetacoplan — especially leading up to its approval days ago — CEO Cedric Francois has often billed its C3 inhibitor as a challenger to Alexion’s blockbuster C5 drug Soliris, and it suggested as much in the pivotal study leading to the FDA’s green light.
But outside the US, there are markets where patients may not have ready access to Soliris. And Apellis says it now has the data suggesting the drug, now branded Empaveli, is just as competitive in the treatment-naïve population.
Reporting topline results from the Phase III PRINCE study, Apellis says Empaveli beat standard of care as a treatment for paroxysmal nocturnal hemoglobinuria in both hemoglobin stabilization and reduction in lactate dehydrogenase after 26 weeks of treatment, meeting the co-primary endpoints. Standard of care, in this context, did not include complement inhibitors.
All told, 86% of those treated with Empaveli were able to avoid a drop of hemoglobin levels above 1 g/dL without transfusions, versus 0% of patients on standard of care (p<0.0001). Mean LDH in the drug group fell by 90% from a baseline of 2151 U/L — which was 9.5 times higher than the upper limit of normal — compared to a 14% reduction on the control arm (p<0.0001).
The trial recruited its 53 participants from Hong Kong, Thailand, Singapore, Malaysia, Philippines, Serbia, Poland, Peru, Mexico and Colombia.
Sobi, the Swedish rare disease company, will be in charge of introducing Empaveli to these places, and more, after paying $250 million upfront to nab ex-US commercialization rights.
“Combined with previous studies, these results emphasize the potential of Empaveli to provide disease control for all adults with PNH regardless of prior treatment,” Federico Grossi, Apellis CMO, said in a statement.
The data were a boost to the broad label Apellis already has, wrote Cowen analyst Phil Nadeau:
Apellis submitted Empaveli for FDA approval based on results from the Phase III PEGASUS study in patients who remained anemic on Soliris, and initiated the PRINCE study in case the label was initially restricted to the treatment-refractory patient population. However, Empaveli’s broad label has made these data supportive rather than imperative; Apellis need not submit an sNDA in order for treatment-naive patients to be considered eligible for treatment.
The companies added that mean hemoglobin levels in the drug arm increased from 9.4 g/dL to 12.1 g/dL, compared to a rise of 8.7 g/dL to 9.4 g/dL (p=0.0019). Among those treated with Empaveli, 91% remained transfusion-free; only 22% in the standard of care group did.
The key to Apellis’ pitch is C3, which it believes can offer a longer-lasting solution for hemoglobin production as C5 often doesn’t boost levels for more than a few days. Starting out in PNH, Apellis and Sobi have mapped out broader plans in geographic atrophy, cold agglutinin disease and hematopoietic stem cell transplantation-associated thrombotic microangiopathy.
In the US and Europe, it will soon find itself going up against AstraZeneca, which has shelled out $39 billion to buy Alexion — both upbeat about Soliris’ blockbuster sales and the potential of follow-on drug Ultomiris.
While an unofficial cross-trial comparison would suggest that Empaveli’s efficacy is comparable to both drugs, Nadeau expects it to be used initially by patients who remain anemic on Soliris or Ultomiris as it launches into a PNH market dominated by Ultomiris.
Social: Cedric Francois, Apellis CEO (Optum via YouTube)