C3G Treatment Landscape Evolves as Novartis and Apellis Near FDA Submissions

Key Insights

• Nephrologists express a strong need for innovative therapies for Complement 3 glomerulopathy (C3G) due to limited long-term solutions and risks associated with current treatments.
• Novartis' Fabhalta (iptacopan) and Apellis' Empaveli (pegcetacoplan) show promise in late-stage trials for C3G, with potential FDA submissions expected in the coming months.
• Clinical trial data for both Fabhalta and Empaveli demonstrate significant reductions in proteinuria and C3c deposit clearance, addressing the underlying mechanisms of C3G.

Complement 3 glomerulopathy (C3G) is a rare, progressive kidney disease marked by inflammation and kidney damage, creating an urgent need for innovative therapies. Current treatments like steroids and immunosuppressants offer limited relief with significant side effects. Data from Spherix Global Insights indicates strong nephrologist interest in new C3G therapies that slow eGFR decline and reduce proteinuria.

Promising Late-Stage Candidates

Novartis' Fabhalta (iptacopan) and Apellis' Empaveli (pegcetacoplan) are late-stage candidates showing promise. Both are already approved for paroxysmal nocturnal hemoglobinuria (PNH), with Fabhalta also approved for IgA nephropathy (IgAN). Phase III trials are underway for C3G, with regulatory submissions anticipated soon. According to Spherix data, treatment preferences will likely be influenced by administration route: Fabhalta is an oral medication taken twice daily, while Empaveli is administered subcutaneously twice weekly.

Clinical Trial Data

At ASN Kidney Week, Novartis presented one-year data from the Phase III APPEAR-C3G trial of Fabhalta (iptacopan), an oral complement inhibitor. The data showed a significant and sustained reduction in proteinuria within 14 days, lasting up to 12 months. The drug met its primary endpoint at six months, and applications for approval have been submitted in the EU, China, and Japan.

Apellis, with European partner Sobi, presented Phase III VALIANT trial data for Empaveli (pegcetacoplan), demonstrating a 68.1% reduction in proteinuria versus placebo. Additionally, 71.4% of treated patients achieved zero C3c staining intensity, indicating C3c deposit clearance. The VALIANT trial included patients with both C3G and IC-MPGN, showing early efficacy by week four.

The Need for New Therapies

Spherix’s Patient Chart Dynamix™ study, analyzing 157 C3G patient records, revealed that physicians would likely treat up to half of their C3G patients with new agents if approved. Nephrologists project that most audited C3G patients are likely to require dialysis within the next ten years, underscoring the critical need for treatments that can delay disease progression and fill gaps in care.