Iptacopan Boosts Hemoglobin Levels in Adults with PNH in Phase 3b Trial

Antonio Risitano, MD, PHD
Credit: Aplastic Anemia and MDS International Foundation

Topline data from the Phase 3b APPULSE-PNH trial reported the benefit of twice daily oral monotherapy iptacopan (Fabhalta) for adult patients with paroxysmal nocturnal hemoglobinuria (PNH) switched from anti-C5 therapies.¹

Announced by Novartis on December 6, 2024, the 24-week treatment results revealed an improvement in the average hemoglobin (Hb) level versus baseline with iptacopan. Safety outcomes remained consistent with previously reported data, according to the company.

“These new results add to the body of evidence reinforcing that [iptacopan] can benefit both patients previously treated with anti-C5 therapies studied in the APPULSE-PNH and APPLY-PNH trials and complement-inhibitor naive patients studied in the APPOINT-PNH trial,” lead trial investigator Antonio Risitano, MD, PHD, Chair of the International PNH Interest Group and Head of the Hematology and Hematopoietic Transplant Unit, Reference Center for Aplastic Anemia and Paroxysmal Nocturnal Hemoglobinuria at the AORN San Giuseppe Moscati, said in a statement.¹

A rare, chronic, and serious complement-mediated blood disorder, PNH is estimated to affect nearly 10 to 20 million people globally.² People with PNH exhibit an acquired mutation in hematopoietic stem cells leading to the production of red blood cells susceptible to premature destruction by the complement system and ultimately, intravascular and extravascular hemolysis.

Iptacopan was developed as an oral, Factor B inhibitor of the alternative complement pathway. The drug was granted US Food and Drug Administration (FDA) approval in December 2023 for treating adults with PNH.³ In August 2024, iptacopan was granted accelerated approval by the FDA for reducing proteinuria in adults with primary immunoglobulin A nephropathy (IgAN), with ongoing development in multiple other complement-mediated diseases.⁴

APPULSE-PNH is a Phase 3b multicenter, single-arm, open-label study evaluating the efficacy and safety of twice-daily oral iptacopan 200 mg in adults with PNH switched from anti-C5 therapies, including eculizumab or ravulizumab. A total of 52 participants received iptacopan for 24 weeks.¹

Enrolled participants were required to be on a stable regimen with anti-C5 therapies for ≥6 months before screening, with average Hb levels of ≥10 g/dL and no red blood cell transfusions during this period. A primary endpoint was the change from baseline Hb levels after 24-week treatment with iptacopan.

Upon analysis, after 24 weeks of treatment with Fabhalta, the average Hb level improved compared with baseline. The safety profile of iptacopan monotherapy was consistent with previously reported data.

“Treatment goals for patients with PNH have greatly evolved, and we can now aim to resolve signs and symptoms of disease in most patients,” Risitano added.¹ “It is promising to see this evolution, and we will continue to make progress to best support these patients.”

Adding to the growing positive body of evidence for iptacopan, Novartis has announced these clinically meaningful data from APPULSE-PNH will be presented at an upcoming 2025 medical meeting.¹

“These data reinforce our confidence in [iptacopan], the first and only oral monotherapy currently available for the treatment of adults with PNH, to provide meaningful hemoglobin improvement, regardless of previous treatment experience,” David Soergel, MD, global head of the cardiovascular, renal and metabolism development unit at Novartis, said in a statement.¹

References

1. _{New phase IIIB data shows Novartis Fabhalta® improved hemoglobin levels in adult patients with paroxysmal nocturnal hemoglobinuria who switched from anti-C5 therapy. Novartis. December 6, 2024. Accessed December 6, 2024. https://www.novartis.com/news/media-releases/new-phase-iiib-data-shows-novartis-fabhalta-improved-hemoglobin-levels-adult-patients-paroxysmal-nocturnal-hemoglobinuria-who-switched-from-anti-c5-therapy.}
2. _{Shah N, Bhatt H. Paroxysmal Nocturnal Hemoglobinuria. [Updated 2023 Jul 31]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK562292/}
3. _{Abigail Brooks M. FDA approves Iptacopan (Fabhalta) for paroxysmal nocturnal hemoglobinuria. HCP Live. December 6, 2023. Accessed December 6, 2024. https://www.hcplive.com/view/fda-approves-iptacopan-fabhalta-for-paroxysmal-nocturnal-hemoglobinuria.}
4. _{Campbell P. IPTACOPAN receives accelerated approval for reducing proteinuria in IGA nephropathy. HCP Live. August 8, 2024. Accessed December 6, 2024. https://www.hcplive.com/view/iptacopan-receives-accelerated-approval-for-reducing-proteinuria-in-iga-nephropathy.}