New Data Reinforce Iptacopan's Role in Transforming PNH Care With Hemoglobin, QOL Gains

Findings revealed significant improvements in average Hb levels over 24 weeks of iptacopan therapy.

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Today, Novartis announced promising topline results from the phase 3B APPULSE-PNH study, demonstrating the efficacy of iptacopan (Fabhalta) as a twice-daily oral monotherapy for adult patients with paroxysmal nocturnal hemoglobinuria (PNH) who transitioned from anti-C5 therapies.¹ The findings revealed significant improvements in average hemoglobin (Hb) levels over 24 weeks of treatment, reinforcing the therapy’s potential as an effective treatment option for patients with PNH, the news release stated.

Phase 3B APPULSE-PNH Study

The study enrolled 52 participants who had been stabilized on anti-C5 therapies (eculizumab or ravulizumab) for at least 6 months prior, with baseline Hb levels of at least 10 g/dL and no recent transfusions. After transitioning to iptacopan, patients experienced an average increase in Hb levels compared with their baseline, further validating iptacopan’s capacity to address anemia—a key challenge in PNH management.

Because patients are typically diagnosed during their prime working years, often while raising young families, it’s not uncommon for symptoms to be dismissed, delaying diagnosis as the disease progresses and anemia worsens with time.²

“These new results add to the body of evidence reinforcing that Fabhalta can benefit both patients previously treated with anti-C5 therapies studied in the APPULSE-PNH and APPLY-PNH trials and complement-inhibitor naïve patients studied in the APPOINT-PNH trial,” APPULSE-PNH trial lead 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, Avellino, Italy, stated.¹ “Treatment goals for patients with PNH have greatly evolved, and we can now aim to resolve signs and symptoms of disease in most patients. It is promising to see this evolution, and we will continue to make progress to best support these patients.”

The safety profile of iptacopan was consistent with previous clinical trials, showcasing its reliability for long-term use in this patient population.

“Across multiple clinical trials, Fabhalta has consistently shown clinically meaningful benefits for patients with PNH, and the APPULSE-PNH trial is a compelling addition to this body of evidence," David Soergel, MD, global head of Cardiovascular, Renal and Metabolism Development Unit at Novartis, said in the statement. “These data reinforce our confidence in Fabhalta, 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.”

Novartis stated that detailed data from the APPULSE-PNH trial will be presented at an upcoming medical meeting in 2025. Beyond its approved indications in the US, EU, Japan, and China for PNH, iptacopan recently received accelerated FDA approval for treating proteinuria in adults with primary immunoglobulin A nephropathy (IgAN).

Max, Novartis Expand PNH treatment Access

According to another announcement today, the Max Foundation, a global nonprofit focused on health equity, has expanded its collaboration with Novartis to provide access to iptacopan for treating PNH in low-resource countries.³ This initiative, part of a partnership spanning 2 decades, will offer treatment at no cost to patients in 53 countries across Sub-Saharan Africa, Latin America, the Caribbean, and parts of Asia.

"We are thrilled to expand our reach to include people living with PNH in low-resource countries without access to an innovative treatment for this life-threatening condition," Pat Garcia-Gonzalez, CEO of Max, said in the announcement. "This collaboration reaffirms the deeply shared value of health equity for both organizations by making the latest treatment approved for the disease available at no cost, fulfilling our mission to accelerate health equity and enabling people to live with dignity and hope."

ASH 2024 Data Show Improved Quality of Life

Additionally, among results from the APPLY-PNH and APPOINT-PNH trials, which will be presented at the American Society of Hematology (ASH) Annual Meeting 2024, iptacopan demonstrated notable improvements in patient-reported health-related quality of life (HRQOL).⁴ This included all functional domains of the EORTC QLQ-C30, global health status, and reductions in key PNH symptoms such as fatigue and dyspnea. In APPLY-PNH, patients switching from anti-C5 therapies to iptacopan reported improvements in HRQOL and symptoms comparable to those initially randomized to iptacopan. Similarly, in APPOINT-PNH, complement inhibitor-naïve patients experienced robust improvements in HRQOL metrics and significant symptom reductions, including hemoglobinuria and fatigue, over 48 weeks.

Investigator-assessed PNH signs and symptoms also showed marked improvement with iptacopan. In APPLY-PNH, the proportion of patients with one or more symptoms decreased from 62.9% at baseline to 25.8% at week 48 in the iptacopan arm. Similarly, APPOINT-PNH participants saw a reduction from 97.5% at baseline to 27.5% at week 48, with substantial increases in the proportion of patients symptom-free. These findings highlight iptacopan’s potential to address both the clinical and quality-of-life needs of PNH patients, providing sustained hemoglobin normalization, transfusion independence, and relief from debilitating symptoms.

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. News release. Novartis. 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. Managing paroxysmal nocturnal hemoglobinuria in an evolving treatment landscape. AJMC^®. August 14, 2024. Accessed December 6, 2024. https://www.ajmc.com/view/managing-paroxysmal-nocturnal-hemoglobinuria-in-an-evolving-treatment-landscape

3. The Max Foundation (Max) expands collaboration with Novartis to include access to innovative treatment for paroxysmal nocturnal hemoglobinuria (PNH). News release. The Max Foundation. December 6, 2024. https://www.prnewswire.com/news-releases/the-max-foundation-max-expands-collaboration-with-novartis-to-include-access-to-innovative-treatment-for-paroxysmal-nocturnal-hemoglobinuria-pnh-302324890.html

4. Risitano AM, Han B, Kulasekaraj AG, et al. Oral iptacopan monotherapy leads to long-term Improvements in patient (Pt)-reported health-related quality of life (HRQoL) and investigator-assessed signs and symptoms of paroxysmal nocturnal hemoglobinuria (PNH): 48-Week (Wk) results from the phase III APPLY-PNH and APPOINT-PNH trials. Paper presented at The American Society of Hematology Annual Meeting 2024; December 9, 2024. San Diego, CA. Session 508.