Apellis targets rare kidney diseases after Phase III pegcetacoplan success

Apellis Pharmaceuticals, in collaboration with Swedish Orphan Biovitrum (Sobi), announced promising Phase III results for their drug, pegcetacoplan, targeting two rare kidney disorders. This breakthrough could potentially open a new market for the complement inhibitor, which has faced challenges related to safety concerns in its existing uses. The findings from the VALIANT trial, which studied pegcetacoplan in patients with C3 glomerulopathy (C3G) and primary immune complex membranoproliferative glomerulonephritis (IC-MPGN), resulted in Apellis' shares increasing by over 12% on Thursday.

Apellis intends to submit a supplemental new drug application to the FDA in early 2025. Concurrently, Sobi plans to file for marketing approval with the European Medicines Agency next year. Currently, pegcetacoplan is approved for treating paroxysmal nocturnal haemoglobinuria (PNH) in both the US and Europe, marketed under the names Empaveli and Aspaveli respectively.

The VALIANT study achieved its primary goal, showing a significant 68% reduction in proteinuria compared to placebo across the study population. This result was consistent regardless of disease type or kidney transplant status. Additionally, the drug exhibited notable improvements in a secondary renal outcome measure combining proteinuria reduction and stabilization of estimated glomerular filtration rate (eGFR), with at least a 50% reduction in proteinuria from baseline.

Jeffrey Eisele, Chief Development Officer at Apellis, expressed great satisfaction with the results, stating, "These results exceeded our already high expectations." He emphasized that pegcetacoplan is the first investigational therapy to demonstrate such a significant reduction in proteinuria in patients with C3G and IC-MPGN, supported by data across various measures of disease activity.

Further details from the VALIANT study will be presented at an upcoming medical congress. The positive trial outcomes could increase competitive pressure on a rival drug from Novartis, Fabhalta (iptacopan), which is also approved for PNH and recently received FDA approval for IgA nephropathy. In a recent Phase III study focusing on C3G, Fabhalta showed a 35.1% relative reduction in proteinuria versus placebo, which is lower than the reduction observed with pegcetacoplan.

In addition to its kidney-related applications, Apellis markets an intravitreal formulation of pegcetacoplan for geographic atrophy (GA) under the brand name Syfovre. However, the drug has encountered issues regarding retinal vasculitis in this indication, complicating the company's market rollout. Apellis later indicated that real-world evidence showed these cases were "very rare," occurring at a rate of 0.01% per injection. Despite this, European regulators recently issued a negative opinion on the GA filing. Apellis is seeking a re-examination, with a final decision anticipated in the fourth quarter.

Financially, Apellis recently reported that Empaveli generated $24.5 million in sales during the second quarter, while Syfovre brought in $154.6 million.

These developments indicate a significant potential for pegcetacoplan to address unmet needs in rare kidney diseases, despite previous setbacks in other indications. The forthcoming regulatory submissions and ongoing trials will be critical for the future market positioning of pegcetacoplan and its impact on Apellis Pharmaceuticals and Sobi.