Novartis’ Fabhalta® (iptacopan) Wins Third FDA Approval for C3G
Novartis has announced that the U.S. Food and Drug Administration (FDA) has approved oral Fabhalta® (iptacopan) for the treatment of adults with C3 glomerulopathy (C3G) to reduce proteinuria. This milestone makes Fabhalta the first and only approved treatment for this debilitating kidney disease, offering hope to patients who previously had limited therapeutic options.
A Groundbreaking Approval for C3G Patients
C3G is a rare and progressive kidney disease that primarily affects young adults, with an average age of diagnosis around 23 years old. The condition is associated with poor long-term outcomes, as approximately 50% of patients progress to kidney failure within 10 years of diagnosis. Until now, patients with C3G had to rely on supportive care, broad immunosuppression, and symptom management without an FDA-approved treatment targeting the underlying disease mechanism.
Dr. Carla Nester, M.D., M.S.A., F.A.S.N., Professor of Pediatrics-Nephrology at the University of Iowa and a co-investigator of the Fabhalta APPEAR-C3G study, emphasized the significance of the approval. “C3G is a debilitating disease often affecting young people, impacting many aspects of their physical and emotional health, and our previous treatment options came with significant challenges,” she said. “This approval of Fabhalta is historic for the entire C3G community as now, for the first time, we have a therapy that is believed to treat the underlying cause of the disease, providing the potential for a new standard of care for patients.”
Fabhalta is the only oral inhibitor of the alternative complement pathway, designed to selectively target what is thought to be the underlying cause of C3G. By doing so, it offers a novel approach to treating the disease, marking a significant advancement in nephrology and rare disease therapeutics.
Patient Perspectives and Impact
Lindsey Fuller, a C3G patient and co-leader of C3G Warriors, shared her perspective on the approval, highlighting the challenges of living with the disease. “As someone whose family has suffered from C3G across multiple generations, it is difficult to fully express the physical and emotional challenges of living with this unrelenting disease,” she said. “To finally have an approved treatment – and one that can be taken orally – is something people with C3G have been waiting for. Today’s approval brings new hope for me, my family, and so many others.”
The symptoms of C3G can significantly impact patients’ quality of life, with fatigue, mobility issues, and mental health challenges such as depression and anxiety being common. The lack of targeted therapies until now has meant that many patients faced uncertain prognoses, often requiring dialysis or kidney transplants at relatively young ages. The approval of Fabhalta marks a transformative moment in the treatment landscape for this rare disease.
Clinical Trial Data Supporting Fabhalta’s Approval
The FDA’s approval of Fabhalta is based on robust data from the pivotal Phase III APPEAR-C3G study, which evaluated the efficacy and safety of twice-daily oral Fabhalta in adult patients with C3G. The study design included a six-month randomized, double-blind treatment period comparing Fabhalta to placebo in addition to supportive care, followed by an additional six-month open-label treatment period where all participants received Fabhalta.
The results demonstrated that treatment with Fabhalta led to a clinically meaningful reduction in proteinuria, which was observed as early as 14 days after treatment initiation and sustained through 12 months. In the open-label extension period, patients who switched from placebo to Fabhalta also experienced a significant reduction in proteinuria, reinforcing the drug’s efficacy.
The safety profile of Fabhalta was favorable, with no new safety signals detected. The most common adverse reactions reported in patients with C3G were nasopharyngitis and viral infections, occurring in at least 10% of patients. Due to the potential risk of serious infections caused by encapsulated bacteria, Fabhalta is available only through a Risk Evaluation and Mitigation Strategy (REMS), which requires specific vaccinations before treatment initiation.
A Broader Vision for Kidney Disease Treatment
Novartis has been at the forefront of kidney disease research, and the approval of Fabhalta represents a crucial step in the company’s broader strategy to address rare and complex renal conditions.
Victor Bultó, President of Novartis U.S., expressed his appreciation for those who contributed to the drug’s development: “We extend our deepest gratitude to the patients and investigators who participated in our clinical trials, without whom this first FDA approval in C3G wouldn’t have been possible. With this additional approval for Fabhalta – the second in kidney disease – we will leverage our established capabilities and expertise to bring this innovative treatment to patients in need as we work to help transform care for people living with kidney diseases.”
Fabhalta has already received regulatory recognition beyond the United States. Last month, the European Medicines Agency (EMA) issued a positive CHMP Opinion recommending approval of Fabhalta for the treatment of C3G. Regulatory reviews are also ongoing in China and Japan, reflecting the global importance of this therapeutic advancement.
Expanding Fabhalta’s Reach Across Kidney Diseases
The approval of Fabhalta for C3G marks its third FDA approval and its second within the Novartis kidney disease portfolio. In August 2024, Fabhalta was granted accelerated approval by the FDA for the reduction of proteinuria in adults with primary immunoglobulin A nephropathy (IgAN) at risk of rapid disease progression. Continued approval for this indication remains contingent on confirmatory clinical data.
Fabhalta originally received its first FDA approval in December 2023 for the treatment of adults with paroxysmal nocturnal hemoglobinuria (PNH), another rare and life-threatening complement-mediated disorder. Beyond these indications, Fabhalta is being actively studied for its potential to treat other rare kidney diseases, including atypical hemolytic uremic syndrome (aHUS), immune complex membranoproliferative glomerulonephritis (IC-MPGN), and lupus nephritis (LN). Ongoing studies aim to further evaluate the drug’s safety and efficacy in these additional conditions.
Novartis’ Broader Commitment to Kidney Disease Research
In addition to Fabhalta, Novartis is advancing the late-stage development of two additional therapies for IgAN, each with highly differentiated mechanisms of action. These include:
- Atrasentan – an investigational oral endothelin A receptor antagonist, which received FDA filing acceptance in Q2 2024. A regulatory decision is anticipated in the first half of 2025.
- Zigakibart – an investigational subcutaneously administered anti-APRIL monoclonal antibody, currently in Phase III development.
These efforts reflect Novartis’ long-term vision to expand therapeutic options for patients with kidney diseases and to pioneer innovative treatments that address the root causes of these conditions. The approval of Fabhalta represents a significant milestone in this journey, offering new hope to C3G patients who previously had no targeted treatment options.
