PNH treatment ruxoprubart shows promise in Phase 2 trial
Antibody therapy cuts need for transfusion, study shows
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Antibody-based therapy ruxoprubart (formerly NM8074) safely prevented blood cell destruction, eased anemia, and eliminated the need for blood transfusions when given as a standalone treatment in adults with paroxysmal nocturnal hemoglobinuria (PNH).
That’s according to results from a Phase 2 trial (NCT05646524) announced by its developer, Novelmed. The trial, started in 2023, is evaluating the therapy’s safety and efficacy in 12 adults with PNH who had not previously received treatment for the disease. Participants receive ruxoprubart by intravenous (into-the-vein) infusions for 13 weeks (about three months) under one of two dosing schedules: 20 mg/kg every two weeks, or 10 mg/kg weekly for the first four weeks, followed by 20 mg/kg every other week.
The company said the Phase 2 study met all efficacy endpoints and showed an “exceptional safety profile,” with ruxoprubart well tolerated during treatment.
Novelmed also said regulators have cleared a Phase 2 study of a subcutaneous (under-the-skin) formulation of ruxoprubart. The planned trial will evaluate a once-weekly, self-administered injection regimen that could allow patients to take the therapy at home rather than receiving intravenous infusions in a clinical setting.
“These milestones validate both our clinical progress and our development strategy,” Rekha Bansal, PhD, Novelmed’s CEO, said in a company press release. “Regulatory clearance of the [subcutaneous] route represents the next logical step toward a patient-friendly treatment option, while our monotherapy data demonstrate the strong, consistent efficacy and tolerability of targeting Bb.” Bb is a protein involved in activating a specific immune pathway that largely drives blood cell destruction in PNH.
Selective blocking
In PNH, a group of proteins of the complement cascade — which normally help fight off bacteria and other infectious agents — attack and destroy healthy blood cells, particularly red blood cells responsible for transporting oxygen through the bloodstream. This can lead to a low number of healthy red blood cells (anemia) and PNH symptoms such as shortness of breath, fatigue, and pain.
Several approved PNH treatments block the activation of the complement cascade to prevent blood cell destruction. The cascade can be triggered through two main pathways: the classical and the alternative pathways. Available therapies generally block both pathways, effectively controlling the disease but potentially increasing the risk of infections.
By targeting the alternative complement protein Bb, Ruxoprubart is designed to selectively block the alternative complement pathway, the one primarily responsible for red blood cell destruction in PNH. Because ruxoprubart leaves the classical pathway intact, the therapy may help control PNH while preserving the body’s natural ability to fight infections.
Early findings from the Phase 2 study suggested the therapy was safe and well-tolerated, prevented blood cell destruction, and reduced the need for blood transfusions, which are often used to ease symptoms caused by low blood cell counts.
Newly shared results confirm the therapy remained well tolerated, with no side effects or serious adverse events reported.
The treatment also proved effective at preventing blood cell destruction. Levels of lactate dehydrogenase (LDH), a marker of blood cell destruction in PNH, were significantly reduced. In addition, red blood cell populations expanded to as much as 94% of their maximum level, consistent with near-complete suppression of complement-mediated red blood cell destruction, known as hemolysis.
These biological effects translated into meaningful clinical outcomes for patients. During weekly dosing, anemia eased, as shown by increases in hemoglobin, the oxygen-carrying protein in red blood cells. Hemoglobin levels rose by 1.5–2.7 grams per deciliter (g/dL), with an average increase of about 2.13 g/dL, reflecting a meaningful improvement from the severely low levels typically seen in untreated PNH.
All patients remained independent of blood transfusions throughout the weekly dosing period, indicating that the therapy controlled hemolysis and alleviated anemia.
Patient-reported outcomes also improved. Quality of life — assessed using the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) scale, which measures fatigue and its impact on daily activities, and questionnaires from the European Organisation for Research and Treatment of Cancer evaluating symptoms, physical functioning, and overall well-being — showed meaningful decreases in fatigue, pain, and overall improvement in functional capacity.
As a subcutaneous injection that patients could self-administer at home, the medication could bring patients more convenience.
“The [Phase 2] intravenous results demonstrate a clinical efficacy and safety profile that aligns well with FDA expectations for monotherapy development in PNH,” said Novelmed’s Robert Bard. “With the [subcutaneous] route now cleared for evaluation under our [Phase 2] program, we are advancing along a well-defined regulatory path. This progress brings us closer to enabling patient-friendly, self-administered treatment options supported by a mechanism designed for pathway-selective precision.”
