Novartis’ Fabhalta Shows Significant Promise in Reducing Proteinuria in Patients with IgA Nephropathy

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Novartis revealed promising data from an analysis of its Phase III APPLAUSE-IgAN trial evaluating Fabhalta (iptacopan) in patients with IgA nephropathy (IgAN). According to the study results, patients treated with Fabhalta demonstrated a 38.3% reduction in proteinuria after 9 months when compared to a placebo. The findings were shared earlier this week at the World Congress of Nephrology in Buenos Aires, Argentina.

The study, which included 250 patients for efficacy analysis and 443 for safety analysis, showed results based on the 24-hour urine protein to creatinine ratio after 9 months of treatment. According to the company, the submission was accepted by the FDA and has been granted priority review.¹

“In IgAN, part of the immune system called the alternative complement pathway can become overly activated in the kidneys, which causes an inflammatory response, leading to progressive kidney damage and gradual loss of kidney function. The loss of kidney function, together with potential side effects of IgAN treatments available until recently, significantly impact patients’ lives,” said Dana Rizk, MD, investigator, APPLAUSE-IgAN steering committee member, professor in the UAB Division of Nephrology, in a press release. “Fabhalta is the first potential treatment for IgAN that specifically targets the alternative complement pathway.”

Last month, Fabhalta received a positive opinion from the Committee for Medicinal Products for Human Use of the European Medicines Agency for the treatment of adults with paroxysmal nocturnal hemoglobinuria (PNH) who also have hemolytic anemia. For this indication, the endorsement was based on data from Novartis’ Phase III APPLY-PNH study in patients with residual anemia despite prior anti-C5 treatment who switched to Fabhalta vs. patients who stayed on anti-C5 treatment, as well as the Phase III APPOINT-PNH study in complement-inhibitor naïve patients. After 24 weeks, results show that 82.3% of anti-C%-experienced patients achieved a sustained increase of Hb levels ≥2 g/dL. Additionally, 92.2% of complement inhibitor-naïve patients using Fabhalta reportedly experienced the same in APPOINT-PNH.²

“With a robust body of evidence and a demonstrated safety profile, Fabhalta could be practice-changing for patients, helping relieve burdens experienced by people living with PNH,” said Antonio Risitano, MD, PhD, president, International PNH Interest Group, head, hematology and Hematopoietic Transplant Unit, Reference Center for Aplastic Anemia and Paroxysmal nocturnal hemoglobinuria, AORN San Giuseppe Moscati, Avellino, Italy, in a press release. “In clinical studies, oral iptacopan demonstrated superior hemoglobin improvement without the need for red blood cell transfusions compared to anti-C5 therapies, leading to normalization of hemoglobin in the majority of patients—a potentially groundbreaking benefit for those living with this chronic blood disorder.”

In December, Fabhalta was given FDA approval for the treatment of adults with PNH, indicated as the first oral monotherapy for this disease. The approval was also based on results of the Phase III APPLY-PNH trial.³

“The US approval of Fabhalta is an extraordinary moment for people living with PNH, their loved ones and the healthcare providers who care for them,” said Victor Bultó, president, US, Novartis, in a press release. “This new, effective oral medicine may mean that patients can reset their expectations of living with PNH, a chronic and life-altering blood disease. As Novartis continues to focus on conditions with unmet patient need, we are exploring the potential of Fabhalta in other complement-mediated diseases—with an ultimate goal to drive meaningful change for patients.”

References

1. New Novartis Fabhalta® (iptacopan) data show clinically meaningful and statistically significant proteinuria reduction of 38.3% versus placebo for patients with IgA nephropathy (IgAN). Novartis. April 15, 2024. Accessed April 17, 2024. https://www.novartis.com/news/media-releases/new-novartis-fabhalta-iptacopan-data-show-clinically-meaningful-and-statistically-significant-proteinuria-reduction-383-versus-placebo-patients-iga-nephropathy-igan

2. Novartis Fabhalta® (iptacopan) receives positive CHMP opinion as first oral monotherapy for adult patients with paroxysmal nocturnal hemoglobinuria (PNH). Novartis. March 22, 2024. Accessed April 17, 2024. https://www.novartis.com/news/media-releases/novartis-fabhalta-iptacopan-receives-positive-chmp-opinion-first-oral-monotherapy-adult-patients-paroxysmal-nocturnal-hemoglobinuria-pnh

3. Novartis receives FDA approval for Fabhalta® (iptacopan), offering superior hemoglobin improvement in the absence of transfusions as the first oral monotherapy for adults with PNH. Novartis. December 6, 2023. Accessed April 17, 2024. https://www.novartis.com/news/media-releases/novartis-receives-fda-approval-fabhalta-iptacopan-offering-superior-hemoglobin-improvement-absence-transfusions-first-oral-monotherapy-adults-pnh