Arrowhead Pharmaceuticals Submits New Drug Application to U.S. FDA for Plozasiran for the Treatment of Familial Chylomicronemia Syndrome
Arrowhead Pharmaceuticals (NASDAQ: ARWR) has submitted a New Drug Application (NDA) to the FDA for plozasiran, targeting familial chylomicronemia syndrome (FCS), a severe genetic disease with no current FDA-approved treatments. The submission is based on positive Phase 3 PALISADE study results, which showed an 80% median reduction in triglycerides and an 83% reduction in acute pancreatitis risk compared to placebo. The company plans to submit additional regulatory applications in 2025. The drug demonstrated promising efficacy in treating FCS, a condition characterized by extremely high triglyceride levels and increased risk of acute pancreatitis.
Arrowhead Pharmaceuticals (NASDAQ: ARWR) ha presentato una Nuova Richiesta di Farmaco (NDA) alla FDA per plozasiran, mirato alla sindrome da chilomicronemia familiare (FCS), una grave malattia genetica senza trattamenti attualmente approvati dalla FDA. La presentazione si basa sui risultati positivi dello studio di Fase 3 PALISADE, che ha mostrato una riduzione mediana del 80% dei trigliceridi e una riduzione dell'83% del rischio di pancreatite acuta rispetto al placebo. L'azienda prevede di presentare ulteriori domande regolatorie nel 2025. Il farmaco ha dimostrato un'efficacia promettente nel trattamento della FCS, una condizione caratterizzata da livelli estremamente elevati di trigliceridi e da un aumento del rischio di pancreatite acuta.
Arrowhead Pharmaceuticals (NASDAQ: ARWR) ha presentado una Nueva Solicitud de Medicamento (NDA) a la FDA para plozasiran, dirigido al síndrome de chilomicronemia familiar (FCS), una enfermedad genética grave sin tratamientos aprobados actualmente por la FDA. La presentación se basa en los resultados positivos del estudio de Fase 3 PALISADE, que mostró una reducción mediana del 80% en los triglicéridos y una reducción del 83% en el riesgo de pancreatitis aguda en comparación con el placebo. La compañía planea presentar solicitudes regulatorias adicionales en 2025. El fármaco demostró una eficacia prometedora en el tratamiento de la FCS, una condición caracterizada por niveles extremadamente altos de triglicéridos y un aumento del riesgo de pancreatitis aguda.
Arrowhead Pharmaceuticals (NASDAQ: ARWR)는 가족성 키로미크론혈증 증후군(FCS)을 치료하기 위해 플로자시란에 대한 새로운 의약품 신청(NDA)을 FDA에 제출했습니다. FCS는 현재 FDA에서 승인된 치료법이 없는 심각한 유전 질환입니다. 이번 신청은 트리글리세리드의 중간값 80% 감소와 급성 췌장염 위험 83% 감소를 보여준 3상 PALISADE 연구의 긍정적인 결과를 바탕으로 하고 있습니다. 이 회사는 2025년에 추가 규제 신청서를 제출할 계획입니다. 이 약물은 트리글리세리드 수치가 매우 높고 급성 췌장염의 위험이 증가하는 FCS 치료에 유망한 효능을 입증했습니다.
Arrowhead Pharmaceuticals (NASDAQ: ARWR) a soumis une Demande de Médicament Nouveau (NDA) à la FDA pour plozasiran, visant le syndrome de chylomicronémie familiale (FCS), une maladie génétique sévère sans traitements actuellement approuvés par la FDA. La soumission est basée sur des résultats positifs de l'étude de Phase 3 PALISADE, qui a montré une réduction médiane de 80% des triglycérides et une réduction de 83% du risque de pancréatite aiguë par rapport au placebo. L'entreprise prévoit de soumettre des demandes réglementaires supplémentaires en 2025. Le médicament a démontré une efficacité prometteuse dans le traitement de la FCS, une condition caractérisée par des niveaux de triglycérides extrêmement élevés et un risque accru de pancréatite aiguë.
Arrowhead Pharmaceuticals (NASDAQ: ARWR) hat einen Antrag auf Zulassung eines neuen Arzneimittels (NDA) bei der FDA für plozasiran eingereicht, das auf das familiäre Chylomikronämiesyndrom (FCS) abzielt, eine schwerwiegende genetische Erkrankung ohne derzeit von der FDA zugelassene Behandlungen. Der Antrag basiert auf positiven Ergebnissen der Phase-3-Studie PALISADE, die eine mediane Reduktion der Triglyceride um 80% und eine Reduktion des Risikos für akute Pankreatitis um 83% im Vergleich zu Placebo zeigte. Das Unternehmen plant, 2025 weitere regulatorische Anträge einzureichen. Das Medikament hat vielversprechende Wirksamkeit bei der Behandlung von FCS gezeigt, einer Erkrankung, die durch extrem hohe Triglyceridwerte und ein erhöhtes Risiko für akute Pankreatitis gekennzeichnet ist.
- Phase 3 PALISADE study met primary endpoint with 80% median triglyceride reduction
- 83% reduction in acute pancreatitis risk compared to placebo
- First-mover advantage with no current FDA-approved treatments for FCS
- Generally well-tolerated safety profile in clinical trials
- Additional regulatory approvals pending until 2025
- Reported adverse events including abdominal pain, COVID-19, nasopharyngitis, and nausea
Insights
The NDA submission for plozasiran represents a significant milestone in treating Familial Chylomicronemia Syndrome (FCS). The Phase 3 PALISADE study demonstrated remarkable efficacy with a
The data shows strong clinical significance: deep and sustained triglyceride reductions, coupled with a favorable safety profile where reported adverse events were generally mild. The dual publication in prestigious journals (Circulation and The New England Journal of Medicine) further validates the robustness of the clinical evidence. If approved, plozasiran could become the first-in-class treatment for FCS, potentially transforming the treatment landscape for this severe genetic condition.
This NDA submission positions Arrowhead Pharmaceuticals for potential market entry in a rare disease space with no current FDA-approved competitors. The addressable market, while niche due to FCS's rare nature, could provide significant revenue potential given typical orphan drug pricing models. The planned expansion to additional regulatory authorities in 2025 indicates a clear commercialization strategy that could drive global market penetration.
The success of plozasiran also validates Arrowhead's TRiM platform technology, potentially increasing the probability of success for their broader pipeline in cardiometabolic, pulmonary, neuromuscular and liver diseases. This milestone could catalyze investor confidence and potentially lead to increased valuation multiples, particularly if approval is granted.
- The New Drug Application is based on positive results from the Phase 3 PALISADE study
- People living with familial chylomicronemia syndrome have extremely high triglyceride levels and a substantially higher risk of developing acute pancreatitis and associated long-term complications, including poor quality of life
- There are currently no FDA approved therapies to treat familial chylomicronemia syndrome
“The NDA submission for investigational plozasiran represents an important milestone for Arrowhead as we advance multiple potential new medicines developed using our proprietary Targeted RNAi Molecule (TRiMTM) platform for patients in diverse therapeutic areas including cardiometabolic, pulmonary, neuromuscular, and liver diseases,” said Chris Anzalone, Ph.D., President and CEO at Arrowhead. “We believe in the potential of RNAi to make a meaningful impact on patients and this first NDA submission is the culmination of over 15 years of innovation and commitment by so many talented Arrowhead employees and the investigators, patients, and caregivers that helped make our vision a reality.”
Bruce Given, M.D., chief medical scientist at Arrowhead, added, “The SUMMIT program of clinical studies of plozasiran has achieved promising and consistent results in various patient populations representing multiple points on the spectrum of elevated triglycerides. FCS represents the most severe end of the spectrum in which many patients have a very poor quality of life and are at high risk of developing acute pancreatitis, which can be life threatening. There are currently no approved therapies in the
The NDA submission is supported by the SUMMIT program of clinical studies of plozasiran and positive findings in the Phase 3 PALISADE study. PALISADE successfully met its primary endpoint and all multiplicity-controlled key secondary endpoints, including statistically significant reductions in triglycerides (TGs), apolipoprotein C-III (APOC3), and the incidence of acute pancreatitis (AP).
In PALISADE, plozasiran achieved deep and durable reductions in triglycerides with a median change from baseline of
The efficacy and safety results from the PALISADE study were presented at the American Heart Association Scientific Sessions 2024 (AHA24) and simultaneously published in Circulation and presented at the European Society of Cardiology (ESC) Congress 2024 and simultaneously published in The New England Journal of Medicine. AHA24, ESC, and other plozasiran presentations may be accessed on the Events and Presentations page in the Investors section of the Arrowhead website.
About Familial Chylomicronemia Syndrome
Familial chylomicronemia syndrome (FCS) is a severe and rare disease often caused by various monogenic mutations. FCS leads to extremely high triglyceride (TG) levels, typically over 880 mg/dL. Such severe elevations can lead to various serious signs and symptoms including acute and potentially fatal pancreatitis, chronic abdominal pain, diabetes, hepatic steatosis, and cognitive issues. Currently, there are no therapeutic options that can adequately treat FCS in the US.
About Plozasiran
Plozasiran, previously called ARO-APOC3, is a first-in-class investigational RNA interference (RNAi) therapeutic designed to reduce production of apolipoprotein C-III (APOC3) which is a component of triglyceride rich lipoproteins (TRLs) and a key regulator of triglyceride metabolism. APOC3 increases triglyceride levels in the blood by inhibiting breakdown of TRLs by lipoprotein lipase and uptake of TRL remnants by hepatic receptors in the liver. The goal of treatment with plozasiran is to reduce the level of APOC3, thereby reducing triglycerides and restoring lipids to more normal levels.
In multiple clinical studies, investigational plozasiran has demonstrated reductions in triglycerides and multiple atherogenic lipoproteins in patients with familial chylomicronemia syndrome (FCS), severe hypertriglyceridemia (SHTG), and mixed hyperlipidemia. Plozasiran has been generally well tolerated to date with treatment emergent adverse events reported that generally reflect the comorbidities and underlying conditions of the study populations. Across clinical studies and study populations, the most frequently reported treatment emergent adverse events for the 25 mg dose that is proposed for marketing approval were COVID-19, upper respiratory tract infection, headache, Type 2 diabetes mellitus, and abdominal pain.
Plozasiran is being investigated in the SUMMIT program of clinical studies, including the PALISADE Phase 3 study in patients with FCS, the SHASTA studies in patients with SHTG, and the MUIR and CAPITAN studies in patients with mixed hyperlipidemia.
Plozasiran in the treatment of patients with FCS has been granted Breakthrough Therapy Designation, Orphan Drug Designation, and Fast Track Designation by the
About PALISADE Phase 3 Study
The PALISADE study (NCT05089084) is a Phase 3 placebo controlled study to evaluate the efficacy and safety of plozasiran in adults with genetically confirmed or clinically diagnosed FCS. The primary endpoint of the study is percent change from baseline in fasting TG versus placebo at Month 10. A total of 75 subjects distributed across 39 different sites in 18 countries were randomized to receive 25 mg plozasiran, 50 mg plozasiran, or matching placebo once every three months. Participants who completed the randomized period were eligible to continue in a 2-part extension period, where all participants receive plozasiran.
About Plozasiran EAP
Arrowhead is committed to bringing new investigational medicines to patients with serious diseases as quickly and efficiently as possible. The company has established an expanded access program (EAP) for some individuals living with FCS. As with any investigational medicine that has not been approved by regulatory authorities, investigational plozasiran may or may not be effective in treating your diagnosis or condition, and there may be risks associated with its use. If you are a patient or caregiver wishing to know more about this plozasiran EAP for FCS, please discuss this EAP and all treatment options with your treating physician. If you are a treating physician and are seeking information about the plozasiran EAP or would like to request access for a patient, please contact EAP@arrowheadpharma.com.
About Arrowhead Pharmaceuticals
Arrowhead Pharmaceuticals develops medicines that treat intractable diseases by silencing the genes that cause them. Using a broad portfolio of RNA chemistries and efficient modes of delivery, Arrowhead therapies trigger the RNA interference mechanism to induce rapid, deep, and durable knockdown of target genes. RNA interference, or RNAi, is a mechanism present in living cells that inhibits the expression of a specific gene, thereby affecting the production of a specific protein. Arrowhead’s RNAi-based therapeutics leverage this natural pathway of gene silencing.
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Source: Arrowhead Pharmaceuticals, Inc.
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Arrowhead Pharmaceuticals, Inc.
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Source: Arrowhead Pharmaceuticals, Inc.
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