Ruxoprubart Shows Efficacy for PNH in Interim Phase 2 Trial Results

New 12-week interim results have been announced in the Phase 2 trial of Ruxoprubart, a novel complement-targeting immunotherapy, for treating paroxysmal nocturnal hemoglobinuria (PNH) in adults.1

Announced by NovelMed on May 19, 2025, these data indicate the safety, tolerability, and efficacy of ruxoprubart. The treatment, typically administered as a monotherapy, reached all primary efficacy endpoints, including transfusion avoidance, increased hemoglobin levels, reduced lactate dehydrogenase (LDH), and increased PNH clone size.1

“The promising interim results from our Phase 2 PNH study solidify ruxoprubart as a novel treatment for patients with advanced hematological conditions, offering hope where existing therapies fall short,” said Rekha Bansal, PhD, chief executive officer of NovelMed. “This achievement not only underscores our commitment to advancing ruxoprubart, an immunotherapy for PNH, but also marks a significant step towards addressing critical unmet needs within this patient population.”1

PNH is a clonal hematopoietic stem cell disorder, typically manifesting with bone marrow failure, hemolytic anemia, and thrombosis. Hemolysis in PNH is a direct result of PNH cells exhibiting a deficiency of complement regulatory proteins. It begins with the expansion of a hematopoietic stem cell with a severe deficiency or absence of GPI, which is a glycolipid moiety that anchors >150 proteins to the cell surface. This leaves red blood cells without protective proteins and vulnerable to complement-mediated destruction.2

Ruxoprubart binds to Bb and selectively inhibits the protease activity of the Alternative Pathway C3 convertase, while maintaining the Classical Pathway. It also provides complete control over both intravascular and extravascular hemolysis by acting proximally in the Alternative Pathway; this resulted in marked hemoglobin level increases during the Phase 2 trial.1

The ongoing 12-week Phase 2 trial is an open-label, multi-dose study in treatment-naïve adult patients with PNH. Primary endpoints include evaluating the safety, tolerability, and efficacy of ruxoprubart as a monotherapy in the alternative pathway-mediated lysis of red blood cells. The trial was initiated after the success of a Phase 1 trial involving 40 healthy volunteers; during this previous trial, ruxoprubart was well tolerated across all dose levels, which ranged from 0.3 to 20 mg/kg, without safety concerns.1

At the time of the announcement, 10 of 12 participants had completed the Phase 2 study. Ruxoprubart cleared all primary efficacy endpoints: ruxoprubart avoided transfusion by successfully protecting PNH Type III cells from Alternative-Pathway-mediated destruction, and hemoglobin was increased above baseline by 1.4 to 2 g/dL in most subjects, with some exhibiting intra-subject increases from 1.5 to 4.3 g/dL.1

An average increase of >1.6 g/dL was observed across the cohort from the beginning to the end of treatment. Ruxoprubart also facilitated LDH reduction by controlling complement-mediated hemolysis, as well as preserving PNH cells by and preventing red blood cell lysis.1

NovelMed has indicated an interest in partnerships to further advance the development of ruxoprubart in other chronic diseases. In the meantime, the company has announced plans to present these findings to regulatory authorities and begin a Phase 3 trial.1

“We are thrilled to share these data, which demonstrate the potential of ruxoprubart in advanced PNH, and look forward to working with regulatory authorities to bring this new immunotherapy to this patient community,” said Robert Bard, Vice President of Regulatory Affairs at NovelMed. “It’s very clear that we are on a promising path with exciting Phase 2 data in this serious hematological disorder.”1

References

1. Phase II Data in Treatment-Naïve Paroxysmal Nocturnal Hemoglobinuria (PNH) Patients: Ruxoprubart Demonstrates Best-in-Class Efficacy as Monotherapy. NovelMed Therapeutics. 19 May 2025. Accessed 19 May 2025. https://www.globenewswire.com/news-release/2025/05/19/3083995/0/en/Phase-II-Data-in-Treatment-Na%C3%AFve-Paroxysmal-Nocturnal-Hemoglobinuria-PNH-Patients-Ruxoprubart-Demonstrates-Best-in-Class-Efficacy-as-Monotherapy.html

2. Brodsky RA. Paroxysmal nocturnal hemoglobinuria. Blood. 2014;124(18):2804-2811. doi:10.1182/blood-2014-02-522128