Pegcetacoplan
- Generic Name
- Pegcetacoplan
- Brand Names
- Empaveli, Syfovre, Aspaveli
- Drug Type
- Biotech
- CAS Number
- 2019171-69-6
- Unique Ingredient Identifier
- TO3JYR3BOU
- Background
Pegcetacoplan is a complement inhibitor indicated in the treatment of paroxysmal nocturnal hemoglobinuria (PNH). Prior to its FDA approval, patients with PNH were typically treated with the C5 inhibiting monoclonal antibody eculizumab. Patients given eculizumab experienced less hemolysis caused by the membrane attack complex, but were still somewhat susceptible to hemolysis caused by C3b opsonization. Pegcetacoplan was developed out of a need for an inhibitor of complement mediated hemolysis further upstream of C5. Pegcetacoplan is a pegylated C3 inhibitor that can disrupt the processes leading to both forms of hemolysis that threaten patients with PNH.
Pegcetacoplan for subcutaneous use was granted FDA approval on 14 May 2021. In February 2023, pegcetacoplan for intravitreal use was approved by the FDA for the treatment of geographic atrophy (GA) secondary to age-related macular degeneration.
- Indication
Pegcetacoplan is indicated to treat adults with paroxysmal nocturnal hemoglobinuria (PNH). It is also indicated to treat geographic atrophy (GA) secondary to age-related macular degeneration.
- Associated Conditions
- Geographic Atrophy Secondary to Age-related Macular Degeneration, Paroxysmal Nocturnal Haemoglobinuria (PNH)
Ruxoprubart Shows Promising Phase II Results as Novel Monotherapy for Paroxysmal Nocturnal Hemoglobinuria
• NovelMed's Ruxoprubart demonstrated significant efficacy in a Phase II trial for treatment-naïve PNH patients, meeting all primary endpoints including complete transfusion avoidance and increased hemoglobin levels.
• The drug's selective inhibition of the Alternative Pathway without affecting the Classical Pathway offers a potentially safer profile than existing treatments, which often carry Black Box warnings for infection risk.
• With FDA Orphan Drug Designation already secured and plans to file for Breakthrough Therapy Designation, Ruxoprubart is positioned as a potential best-in-class therapy for PNH and other complement-mediated disorders.
Boehringer Ingelheim Launches Phase II Trial of First-in-Class Oral Treatment for Geographic Atrophy
• Boehringer Ingelheim has initiated the JADE Phase II clinical study to evaluate BI 1584862, a potential first-in-class oral treatment for geographic atrophy, a severe form of age-related macular degeneration.
• Geographic atrophy affects over 5 million people worldwide with more than 40% considered legally blind, creating a significant unmet need for treatments that can slow disease progression and preserve vision.
• The company is simultaneously advancing a second compound, BI 771716, an antibody fragment designed to penetrate retinal layers, demonstrating Boehringer's dual-pathway approach to addressing this debilitating eye condition.
Novartis' FABHALTA Poised to Transform Treatment Landscape for Multiple Complement-Mediated Diseases
• FABHALTA (iptacopan), Novartis' first-in-class oral factor B inhibitor, has received FDA approvals for paroxysmal nocturnal hemoglobinuria (PNH), IgA nephropathy (IgAN), and C3 glomerulopathy (C3G), marking a significant shift from traditional intravenous therapies.
• The drug's oral administration route and ability to control both intravascular and extravascular hemolysis addresses key limitations of current therapies, potentially expanding the market for complement-targeted treatments estimated at over $1.2 billion in 2024.
• With patent protection extending to 2041 and ongoing investigations for additional indications including myasthenia gravis and atypical hemolytic uremic syndrome, FABHALTA is expected to significantly reshape the complement inhibitor market landscape.
Character Biosciences Secures $93M to Advance Precision Therapies for Age-Related Macular Degeneration
• Character Biosciences has raised $93 million in Series B funding to advance two drug candidates for age-related macular degeneration (AMD) into clinical trials this year.
• The company's lead candidates include CTX114, targeting geographic atrophy, and CTX203, designed to prevent progression in intermediate AMD patients by regulating lipid transport.
• Character's precision medicine approach involves analyzing data from over 6,500 AMD patients to identify genetic subtypes, potentially improving upon current treatments like Syfovre and Izervay.
Novartis's Fabhalta Rapidly Reshapes PNH Treatment Landscape as Biosimilars Loom
• Fabhalta (Novartis) has gained significant market share in just 15 months since its December 2023 launch, with physician consideration for first-line use doubling year-over-year in the PNH treatment space.
• Hematologists increasingly believe all PNH patients should receive complement or factor inhibitor therapy regardless of disease burden, with oral treatment options becoming more attractive due to adherence benefits.
• Upcoming biosimilar versions of eculizumab (Bkemv from Amgen and Epysqli from Samsung Bioepis) could disrupt the market, with physicians projecting up to half of Soliris patients may switch by end of 2025.
Zervimesine Shows Promise in Geographic Atrophy Trial, Building on Success in Multiple CNS Disorders
• Cognition Therapeutics' Phase 2 MAGNIFY trial of zervimesine demonstrates slower lesion growth in geographic atrophy patients compared to placebo after 6 months of treatment.
• The drug previously showed significant benefits in dementia with Lewy bodies trials, with patients showing 86% improvement in neuropsychiatric symptoms and 62% better motor function versus placebo.
• Zervimesine also demonstrated strong results in Alzheimer's disease trials, achieving a 95% reduction in cognitive decline in a biomarker-defined subgroup compared to placebo.
UK Biotech Secures €72M Series A to Advance Novel Gene Therapy for Geographic Atrophy
• Complement Therapeutics has raised €72 million ($79M) in Series A funding to advance CTx001, a single-injection gene therapy targeting geographic atrophy, into Phase 1b clinical trials.
• The University of Manchester spinout is developing an AAV-based therapy to address geographic atrophy, an advanced form of AMD affecting 8 million people globally with limited treatment options.
• The company has initiated a natural history study (i-GAIN) and partnered with Pharmaron for AAV manufacturing, targeting first-in-human trials in late 2024.
EMA Validates Aspaveli® Extension Application for Rare Kidney Diseases C3G and IC-MPGN
• The European Medicines Agency has validated the application to extend Aspaveli® (pegcetacoplan) use for treating C3 glomerulopathy and primary immune complex membranoproliferative glomerulonephritis, two rare kidney diseases currently lacking approved treatments.
• Phase 3 VALIANT study demonstrated significant 68% reduction in proteinuria with pegcetacoplan compared to placebo (p<0.0001), along with stabilization of kidney function and reduced C3c staining intensity.
• The potential approval could provide the first targeted treatment for approximately 8,000 European patients affected by these conditions, with possible US launch in second half of 2025.
Astellas Seeks First Japanese Approval for Geographic Atrophy Treatment with Avacincaptad Pegol
• Astellas Pharma has submitted a New Drug Application to Japan's MHLW for avacincaptad pegol, potentially becoming the first approved treatment for geographic atrophy in Japan.
• The submission is supported by GATHER1 and GATHER2 clinical trials, which demonstrated the drug's ability to slow GA lesion growth with a favorable safety profile over two years.
• Geographic atrophy affects over 5 million people globally, with 66% at risk of becoming legally blind without treatment, highlighting the significant unmet medical need.
Apellis' Syfovre Approved in Australia for Geographic Atrophy
• Apellis Pharmaceuticals' Syfovre (pegcetacoplan) has been approved in Australia for treating geographic atrophy (GA) secondary to age-related macular degeneration (AMD).
• Syfovre is the first and only approved treatment for GA in Australia, offering a new option to slow the progression of this irreversible vision loss.
• The approval is based on Phase 3 OAKS and DERBY studies, which demonstrated that Syfovre slowed GA progression with a generally well-tolerated safety profile.
• Affecting over 75,000 Australians, GA leads to progressive vision loss, impacting independence and quality of life, making this approval a significant advancement.
Clinical Trial Industry Faces Complex Challenges in 2025: Adaptive Designs, Political Shifts, and Diversity Requirements
• Clinical trials are becoming increasingly complex and expensive as they target smaller patient populations and face stricter regulations, driving the need for smarter and more efficient trial designs.
• Political changes, including Trump's presidency, could lead to significant regulatory shifts in the clinical trial landscape, potentially affecting approval pathways and oversight mechanisms.
• New legislation like the Inflation Reduction Act is expected to impact trial initiations and drug development, while diversity guidelines from WHO, FDA, and EMA present both opportunities and challenges for patient recruitment.
FDA Rejects Astellas' Label Update for Geographic Atrophy Drug Izervay
• The FDA issued a complete response letter for Astellas' Izervay label update, which included data from the Phase 3 GATHER2 trial, impacting its competitive positioning.
• The FDA's rejection was based on a statistical matter related to the proposed labeling language, with no concerns raised regarding the drug's safety or efficacy data.
• This setback follows Astellas' withdrawal of Izervay's marketing application in the EU, further complicating the drug's global market access.
• Izervay, a complement C5 inhibitor, is currently approved in the US for geographic atrophy secondary to age-related macular degeneration.
Novartis and Apellis Advance C3G Therapies Towards FDA Submission
• Novartis' Fabhalta (iptacopan) demonstrated significant proteinuria reduction in the Phase III APPEAR-C3G trial, meeting its primary endpoint and supporting regulatory submissions.
• Apellis' Empaveli (pegcetacoplan) showed a substantial reduction in proteinuria and C3c deposit clearance in the Phase III VALIANT trial, indicating early efficacy in C3G patients.
• Nephrologists express a strong interest in new C3G therapies that can slow eGFR decline and reduce proteinuria, addressing the urgent need for innovative treatments.
• Spherix data suggests treatment preferences may be influenced by administration route, with Fabhalta's oral administration potentially offering an advantage.
Astellas Withdraws EU Filing for Geographic Atrophy Drug Avacincaptad Pegol
• Astellas has withdrawn its EMA filing for avacincaptad pegol (Izervay) for geographic atrophy (GA) following feedback from the CHMP.
• The decision is a setback after Astellas' $5.9 billion acquisition of Iveric Bio, the drug's developer, last year.
• Avacincaptad pegol is already approved in the US as Izervay for GA secondary to age-related macular degeneration (AMD).
• Astellas remains committed to bringing avacincaptad pegol to market in Europe and is assessing the financial impact of the withdrawal.
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