Pegcetacoplan

--- Ruxoprubart (NM8074) met all clinical endpoints, offering a safe, differentiated treatment for Paroxysmal Nocturnal Hemoglobinuria (PNH). Paroxysmal Nocturnal Hemoglobinuria (PNH) is a rare hematological (Blood) disorder. Regulatory approval for the Phase II trial in PNH subjects was granted based on the safety profile of healthy subjects in the Phase I trial. Interim results from this 12-subject, three-month, multi-dose Phase II efficacy trial are compelling. The drug was safe and well-tolerated in all treated PNH subjects with expected safety & efficacy, meeting all clinical endpoints with no reported side effects. In this efficacy trial, Ruxoprubart: Protected PNH Red Blood cells against lysis and enabled complete transfusion avoidance, meeting the primary endpoint. Increased hemoglobin levels above baseline by 1.4 to 2.0 g/dL in most subjects, with some showing intra-subject hemoglobin increase of 1.5 to 4.3 g/dL, exceeding the threshold set for the primary endpoint. An average hemoglobin increase of >1.6 g/dL was observed across the cohort from baseline to the end of the treatment period. Reduced LDH levels to baseline, meeting the primary efficacy endpoint. Significantly increased PNH Type III clone size by protecting PNH Red Blood Cells from complement-mediated lysis. Allowed normal pathogenic clearance in all treated PNH subjects, as infection cleared as expected. The regulatory agency has recently approved a once-weekly subcutaneous protocol for Ruxoprubart — allowing for self-administration and offering a distinct advantage over Apellis, which requires twice-weekly dosing. Ruxoprubart effectively inhibited the Alternative Pathway (AP) without affecting the Classical Pathway (CP) in the trial. More importantly, the FDA has granted Orphan Drug Designation (ODD) to Ruxoprubart for treating PNH. A Breakthrough Therapy Designation (BTD) application for Ruxoprubart in PNH will soon be filed for FDA review. Ruxoprubart is set to be developed as a novel treatment for several complement-mediated disorders, including but not limited to renal, hematological, dermatological, and ocular diseases. CLEVELAND, May 19, 2025 (GLOBE NEWSWIRE) -- NovelMed is pleased to announce positive 12-week interim results from the ongoing multi-dose Phase II trial of Ruxoprubart, a novel complement-targeting immunotherapy, in adult patients with Paroxysmal Nocturnal Hemoglobinuria (PNH). These interim data demonstrate that Ruxoprubart, administered as monotherapy, was safe, well-tolerated, and met all primary efficacy endpoints. Ruxoprubart achieved transfusion avoidance, increased hemoglobin levels, reduced LDH, and increased PNH clone size — key outcomes that contributed to improved disease control and enhanced quality of life for PNH patients. “The promising interim results from our Phase II PNH study solidify Ruxoprubart as a novel treatment for patients with advanced hematological conditions, offering hope where existing therapies fall short. This achievement not only underscores our commitment to advancing Ruxoprubart, an immunotherapy for PNH, but also marks a significant step toward addressing critical unmet needs within this patient population," said Dr. Rekha Bansal, CEO. "I extend my sincere gratitude to the PNH subjects and investigators whose dedication has been instrumental in this success. We are eager to present our findings to regulatory authorities and proceed with the Phase III trial." Figure. NovelMed Scientist Prepares Complement Test Assays to Support Clinical Development of Ruxoprubart (NM8074) for Paroxysmal Nocturnal Hemoglobinuria (PNH). Ruxoprubart works by binding to Bb and selectively inhibiting the protease activity of the Alternative Pathway C3 convertase, while preserving the Classical Pathway. By acting proximally in the Alternative Pathway, Ruxoprubart provides complete control over both intravascular and extravascular hemolysis, resulting in marked increases in hemoglobin levels observed in this trial. These findings support the drug’s advancement as a novel, next-generation immunotherapy for the treatment of PNH and a broad range of hematological, renal, inflammatory, and ocular diseases. “We are excited to announce that our Alternative Pathway strategy for treating PNH is delivering exceptional results,” said Mr. Alex Kumar, Chief Strategy Advisor at NovelMed. “These data reinforce our confidence as we look forward to working with the regulatory agency to bring Ruxoprubart to PNH patients without delay. Our mission is to transform the lives of chronically ill patients for whom an ideal treatment has yet to be discovered.” Clinical Study Overview and Efficacy Summary in PNH This Phase II trial was initiated following the successful completion of a Phase I study involving 40 (forty) healthy volunteers. Ruxoprubart was well tolerated across all dose levels, ranging from 0.3 to 20 mg/kg, with no safety concerns. The drug demonstrated selective inhibition of the Alternative Pathway through Bb binding, without affecting the Classical Pathway. These promising safety findings paved the way for regulatory approval to initiate a Phase II study in patients with PNH. This ongoing 12-week clinical trial of Ruxoprubart is an open-label, multi-dose study in treatment-naïve adult subjects with PNH. The primary objectives are to evaluate the safety, tolerability, and efficacy of Ruxoprubart as a monotherapy in the Alternative Pathway-mediated lysis of Red Blood Cells. To date, 10 out of 12 PNH subjects have completed the study. Subjects 11 & 12 have been enrolled to complete the two-cohort trial. Interim results confirm that Ruxoprubart achieved all primary efficacy endpoints, delivering sustained clinical benefit in PNH. The primary efficacy endpoints include: Transfusion Avoidance : PNH patients typically require multiple blood transfusions to maintain normal hemoglobin levels. Ruxoprubart effectively protected PNH Type III cells from Alternative Pathway-mediated destruction, resulting in complete transfusion avoidance and successfully meeting the primary efficacy endpoint. Hemoglobin Increase : PNH patients experience reduced hemoglobin levels, leading to severe anemia. Ruxoprubart increased hemoglobin levels above baseline by 1.4 to 2.0 g/dL in most subjects, with some showing intra-subject increases ranging from 1.5 to 4.3 g/dL, surpassing the efficacy threshold defined for the primary endpoint. An average increase of >1.6 g/dL in hemoglobin was observed across the cohort from the beginning to the end of the treatment period. LDH Reduction : PNH patients experience severe lysis of Red Blood Cells (RBCs), leading to elevated lactate dehydrogenase (LDH) levels. By controlling complement-mediated hemolysis, Ruxoprubart reduced LDH levels to baseline, achieving the primary efficacy endpoint. Preservation of PNH Cells : Continuous lysis of Red Blood Cells in PNH leads to a dramatic reduction in total RBC count, often exceeding 80 to 90%. By effectively preventing this lysis, Ruxoprubart significantly preserved PNH cells, resulting in a substantial increase in the total PNH clone size and hemoglobin, successfully meeting the primary efficacy endpoint. Pathogenic Clearance : As expected, Ruxoprubart facilitated effective pathogenic clearance across all treated PNH subjects. In summary, the observed changes in efficacy parameters support the drug's mechanism of action and validate Ruxoprubart’s potential as a highly effective monotherapy for PNH. “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 Mr. Robert Bard, Vice President of Regulatory Affairs at NovelMed. “It’s very clear that we are on a promising path with exciting Phase II data in this serious hematological disorder.” Paroxysmal Nocturnal Hemoglobinuria (PNH) PNH is a rare, acquired hematologic disorder in which Red Blood Cells lack protective surface proteins due to a mutation in the phosphatidylinositol glycan class A (PIGA) gene, leaving them vulnerable to complement-mediated destruction. In healthy individuals, Type I RBCs express complement regulatory proteins and are fully protected from complement-mediated destruction. In contrast, PNH patients have a significant percentage of Type III RBCs, which completely lack these protective proteins and are therefore highly susceptible to Alternative Pathway-mediated lysis. PNH is primarily an Alternative Pathway-mediated disease, with no involvement of the Classical or Lectin pathways in its pathology. Key laboratory markers indicative of disease progression include reduced Type III Red Blood Cells, low hemoglobin, elevated lactate dehydrogenase (LDH), and an increased need for blood transfusions. These markers reflect the underlying hemolytic anemia, which in turn leads to debilitating symptoms such as chronic fatigue, pain, jaundice, and organ damage. As the disease progresses, it significantly affects the patient’s quality of life and can ultimately result in life-threatening complications and death if not properly managed. While Soliris® (eculizumab) is the current FDA-approved standard of care for PNH – administered via intravenous infusion to provide C5 blockade – clinical limitations persist. Up to 88% of Soliris-treated patients continue to experience persistent anemia, with more than one-third of them requiring blood transfusions at least once every year. Despite its effectiveness in some patients, Soliris does not fully address the needs of many patients, as a significant proportion remain anemic, fatigued, and require blood transfusions, highlighting the need for specific, effective, and comprehensive therapies. Nearly all FDA-approved therapies for PNH and other complement-mediated disorders, oral or intravenous, suffer from the well-documented Black Box warning label because of the broad immunosuppression of the Classical Pathway, elevating the risk of life-threatening infections. Ruxoprubart offers a selective, upstream, and targeted approach to Alternative Pathway inhibition, without compromising the Classical Pathway, offering the best-in-class novel therapy. These attributes position Ruxoprubart as a safer and more effective treatment for patients with PNH. Ruxoprubart (NM8074) Ruxoprubart, an engineered human immunoglobulin, exhibits dual specificity: 1) it blocks only the Alternative Pathway, dysregulated by the disease, and 2) it binds Bb which has no binding to Factor B. Ruxoprubart met all primary endpoints in the interim evaluation of the ongoing Phase II clinical trial in PNH, positioning it as the first immunotherapy in this indication with the potential for approval without a Black Box warning. This immunotherapy has demonstrated a safe and well-tolerated profile across all five cohorts in the Phase I trial, including the highest dose of 20 mg/kg. Our findings confirm that the drug selectively blocks the Alternative Pathway. This differentiated, novel mechanism sets Ruxoprubart apart from other complement blockers (Soliris®, Ultomiris®, Empaveli®, Voydeya®, and Fabhalta®) currently approved or in development worldwide. Voydeya®, which received FDA approval in 2024 as a combination therapy, was developed by Achillion and acquired by AstraZeneca for $930 million. Despite its limited clinical efficacy, Voydeya®'s reliance on co-administration with a C5 inhibitor restricts its potential as a standalone therapy. Unlike Fabhalta®, which targets Factor B, Ruxoprubart (NM8074) binds to Bb, which is generated only upon activation of the Alternative Pathway, offering a unique mechanism of action as monotherapy. As a novel monotherapy with a unique, upstream, and pathway-specific mechanism, Ruxoprubart is emerging as a best-in-class candidate for the treatment of PNH and numerous complement-mediated diseases. NovelMed Therapeutics ( www.novelmed.com ) NovelMed is a clinical-stage biopharmaceutical company dedicated to developing innovative novel biologics (immunotherapies) to treat a wide range of complement-mediated diseases. NovelMed proudly leads the development of Alternative Pathway-specific antibodies (NM8074, NM5072, and NM8070) to address a wide range of chronic complement-mediated disorders. The company is actively conducting a Phase II clinical trial in treatment-naïve PNH subjects to expedite the availability of this promising treatment. Additionally, the FDA has approved Phase II studies for several rare diseases, including but not limited to Atypical Hemolytic Uremic Syndrome (aHUS), C3 Glomerulopathy (C3G), IgA Nephropathy (IgAN), ANCA-Associated Vasculitis (AAV), and Dermatomyositis (DM). We are committed to delivering life-changing therapies to patients across hematology, ophthalmology, nephrology, dermatology, and neurology. NovelMed is currently seeking partnerships to advance the development of Ruxoprubart to approval in several chronic diseases. We are open to discussions regarding investment, out-licensing, or acquisition. For more details regarding our progress, please visit www.novelmed.com/news . Watch our introductory Video to learn more about NovelMed. Contact: Ya Gao, MS NovelMed Communication Team BD@novelmed.com (216) 440 2696 Figure. NovelMed Scientist Prepares Clinical Trial Samples for Analysis https://www.globenewswire.com/NewsRoom/AttachmentNg/ae2c0bfc-ff88-486d-a796-f2977947c8a4 Figure. NovelMed Scientist Prepares Clinical Trial Samples for Analysis Figure. NovelMed Scientist Prepares Clinical Trial Samples for Analysis (Available at https://www.globenewswire.com/NewsRoom/AttachmentNg/ae2c0bfc-ff88-486d-a796-f2977947c8a4) Legal Disclaimer: EIN Presswire provides this news content "as is" without warranty of any kind. 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Syfovre’s sales performance in the quarter fell well below Mizuho Securities’ forecast of $157 million, with analysts at the firm stating the miss was “worse than we could have envisioned.” Despite holding the lead with its complement inhibitor Syfovre, Apellis Pharmaceuticals is discovering that the geographic atrophy market is a tough nut to crack.Syfovre—which became the first medication specifically approved by the FDA for geographic atrophy (GA) in early 2023—posted U.S. sales of $130.2 million during the first three months of 2025, down 22% quarter over quarter and 3% versus the same period in 2024.Despite increases in patient demand in recent months, Syfovre's revenue totals have suffered from funding shortfalls at copay assistance programs and inventory fluctuations, Apellis CEO Cedric Francois, M.D., Ph.D., said in a statement.Syfovre’s sales performance in the quarter fell well below Mizuho Securities’ forecast of $157 million, with analysts at the firm stating the miss was “worse than we could have envisioned.”Taking various challenges into account—from safety questions and stalling class growth to copay assistance struggles—the Mizuho team now envisions “persistent challenges for Syfovre’s uptake” in both the short- and long-term.Although Apellis executives had previously suggested that seasonality and inventory issues affecting Syfovre in the first quarter were one-off factors, the company noted on its earnings call last week that it now expects the fallout of underfunded copay assistance programs to bleed into the rest of the year.Apellis didn't get into details about the copay funding shortfall, but online sources indicate that there have been major disruptions in the ophthalmology space amid funding challenges for such programs.Underfunding of copay assistance programs—which Regeneron’s CEO also lamented on his company’s earnings call last month—has forced Apellis to give away more Syfovre samples. The company now figures that its current sampling rate of roughly 10,000 vials per quarter will become the norm, versus a previous rate of around 5,000 vials per quarter, analysts at Evercore ISI wrote in a recent note to clients.While Apellis could scale that number back, it’s “not clear when that could happen,” the Evercore team said.In turn, the Mizuho team has dialed back its overall expectations for the drug, now predicting Syfovre will hit an annual sales peak of $1.08 billion in 2033. Mizuho’s trimmed forecast stands 16% below the current consensus estimate for peak Syfovre sales of $1.29 billion in 2033. Overall, Apellis delivered $166.8 million in total sales for the first quarter, down roughly 3% compared to the same three-month stretch in 2024. Even as Syfovre took a hit, the company’s other commercial product, Empaveli, struggled too, though the drug still has room to recover, the Mizuho team said.Empaveli, which is underpinned by the same molecule, pegcetacoplan, as its sibling Syfovre, pulled down $19.7 million in first-quarter sales. That revenue haul was down 23% year over year and failed to meet Mizuho’s forecasted $24 million for the period.Nevertheless, the “spotlight shifts to Empaveli” now that Syfovre faces several challenges, the Mizuho team said.In August, Empaveli is up for an FDA approval verdict in two rare kidney indications—complement 3 glomerulopathy (C3G) and primary immune complex membranoproliferative glomerulonephritis (IC-MPGN)—that affect roughly 5,000 patients in the United States and 8,000 in Europe, the Mizuho analysts noted.Mizuho further predicts Empaveli will hit peak sales of roughly $350 million in C3G/IC-MPGN, should it win approval.Apellis’ Syfovre struggles—and those facing the GA market more broadly—aren’t new, though the drug’s latest sales miss is much more acutely felt than the stagnation it endured in previous quarters.Meanwhile, Astellas’ Izervay is experiencing growing pains, too, with the Japanese drugmaker in February reporting that sales growth had slowed to just 4% in the last three months of 2024, despite the drug being early in its launch. Izervay debuted roughly six months after Syfovre’s launch in 2023. Still, Apellis’ top brass appears confident in their ability to unlock the GA market, at least for now.“We are still in the early phases of growth and estimate that only half of diagnosed GA patients are seen by an eyecare professional. Of those, less than 10% are receiving treatment,” Apellis’ CEO Francois said in late February. “Building a new market takes time.”