Agios Completes Enrollment of Phase 3 RISE UP Study of Mitapivat in Sickle Cell Disease
Agios Pharmaceuticals (AGIO) has completed enrollment for its Phase 3 RISE UP study evaluating mitapivat in sickle cell disease patients aged 16 and older. The global trial enrolled over 200 patients, with topline results expected in late 2025. The study's primary endpoints focus on hemoglobin response and annualized rate of sickle cell pain crises. Mitapivat, an oral PK activator, is designed to optimize the glycolytic pathway by increasing ATP levels and decreasing 2,3-DPG concentrations in red blood cells, potentially addressing the underlying mechanisms of sickle cell disease.
Agios Pharmaceuticals (AGIO) ha completato l'arruolamento per il suo studio di Fase 3 RISE UP che valuta mitapivat nei pazienti con anemia falciforme di età pari o superiore a 16 anni. Lo studio globale ha arruolato oltre 200 pazienti, con risultati preliminari attesi entro la fine del 2025. I principali obiettivi dello studio si concentrano sulla risposta dell'emoglobina e sulla frequenza annualizzata delle crisi dolorose legate all'anemia falciforme. Mitapivat, un attivatore della PK orale, è progettato per ottimizzare la via glicolitica aumentando i livelli di ATP e riducendo le concentrazioni di 2,3-DPG nei globuli rossi, affrontando potenzialmente i meccanismi sottostanti della malattia.
Agios Pharmaceuticals (AGIO) ha completado el reclutamiento para su estudio de Fase 3 RISE UP que evalúa mitapivat en pacientes con enfermedad de células falciformes de 16 años o más. El ensayo global reclutó a más de 200 pacientes, con resultados preliminares esperados a finales de 2025. Los objetivos principales del estudio se centran en la respuesta de hemoglobina y la tasa anualizada de crisis de dolor relacionadas con la enfermedad de células falciformes. Mitapivat, un activador de PK oral, está diseñado para optimizar la vía glucolítica aumentando los niveles de ATP y disminuyendo las concentraciones de 2,3-DPG en los glóbulos rojos, lo que podría abordar los mecanismos subyacentes de la enfermedad.
Agios Pharmaceuticals (AGIO)는 16세 이상의 겸상적혈구병 환자들을 대상으로 mitapivat를 평가하는 3상 RISE UP 연구의 환자 등록을 완료했습니다. 이 글로벌 시험에는 200명 이상의 환자가 등록되었으며, topline 결과는 2025년 말에 발표될 예정이다. 연구의 주요 목표는 헤모글로빈 반응과 겸상적혈구 통증 위기의 연간 발생률에 초점을 맞추고 있습니다. Mitapivat는 경구 PK 활성제로, ATP 수치를 증가시키고 적혈구의 2,3-DPG 농도를 감소시킴으로써 해당 병의 근본적인 메커니즘을 해결할 수 있도록 설계되었습니다.
Agios Pharmaceuticals (AGIO) a terminé le recrutement pour son étude de phase 3 RISE UP évaluant mitapivat chez des patients atteints de drépanocytose âgés de 16 ans et plus. L'essai mondial a recruté plus de 200 patients, avec des résultats préliminaires attendus fin 2025. Les principaux objectifs de l'étude se concentrent sur la réponse en hémoglobine et le taux annualisé des crises douloureuses liées à la drépanocytose. Mitapivat, un activateur de PK oral, est conçu pour optimiser la voie glycolytique en augmentant les niveaux d'ATP et en diminuant les concentrations de 2,3-DPG dans les globules rouges, ce qui pourrait aborder les mécanismes sous-jacents de la maladie.
Agios Pharmaceuticals (AGIO) hat die Rekrutierung für seine Phase-3-Studie RISE UP abgeschlossen, die mitapivat bei Patienten mit Sichelzellenanämie im Alter von 16 Jahren und älter bewertet. Die globale Studie rekrutierte über 200 Patienten, und die vorläufigen Ergebnisse werden Ende 2025 erwartet. Die Hauptziele der Studie konzentrieren sich auf die Hämoglobinreaktion und die annualisierte Rate von Schmerzkrisen bei Sichelzellenanämie. Mitapivat, ein oraler PK-Aktivator, ist darauf ausgelegt, den glykolytischen Weg zu optimieren, indem es die ATP-Spiegel erhöht und die 2,3-DPG-Konzentrationen in den roten Blutkörperchen verringert, was potenziell die zugrunde liegenden Mechanismen der Sichelzellenanämie anspricht.
- Successfully completed enrollment of over 200 patients in Phase 3 RISE UP study
- Building on positive Phase 2 RISE UP study results presented at ASH 2023
- Addresses critical unmet need in sickle cell disease treatment market
- Topline data not available until late 2025
- No guarantee of positive Phase 3 trial outcomes
Insights
The completion of enrollment for the Phase 3 RISE UP study marks a significant milestone in developing a potential new treatment for sickle cell disease. The trial includes over 200 patients and focuses on two critical endpoints: hemoglobin response and reduction in pain crises frequency - both fundamental quality-of-life indicators for patients.
The study's design is particularly robust, being double-blind, randomized and placebo-controlled. Mitapivat's unique mechanism of action targeting the glycolytic pathway represents an innovative approach to treating sickle cell disease by addressing both ATP production and 2,3-DPG levels. The previous Phase 2 results presented at ASH 2023 provided encouraging data to support this larger trial.
However, investors should note that final results won't be available until late 2025, indicating a significant waiting period before any potential commercialization. The market opportunity is substantial given the lifelong nature of sickle cell disease and the current treatment options.
– Topline Data from 52-week Phase 3 Study Expected in Late 2025 –
CAMBRIDGE, Mass., Oct. 23, 2024 (GLOBE NEWSWIRE) -- Agios Pharmaceuticals, Inc. (Nasdaq: AGIO), a leader in cellular metabolism and pyruvate kinase (PK) activation pioneering therapies for rare diseases, today announced that enrollment is complete for the Phase 3 RISE UP study. This global, double-blind, randomized, placebo-controlled trial is evaluating the efficacy and safety of mitapivat, an oral, small molecule PK activator, in sickle cell disease patients who are 16 years of age or older. Agios expects to report topline results from this 52-week Phase 3 study in late 2025.
Sickle cell disease is an inherited, lifelong blood disorder caused by mutations in hemoglobin, the major protein that carries oxygen in red blood cells. In sickle cell disease, red blood cells are sickle-shaped due to a gene mutation that affects the hemoglobin molecule. When red blood cells sickle, they do not bend or move easily and can block blood flow to the rest of the body, resulting in chronic hemolytic anemia, pain, poor quality of life, organ damage and early mortality. In sickle cell disease there is an increased energy demand of adenosine triphosphate (ATP) to support red blood cell function and increased 2,3-diphosphoglycerate (2,3-DPG) concentrations that increase the likelihood of red blood cell sickling. Mitapivat is designed to optimize the glycolytic pathway, which has a dual effect of increasing ATP levels and decreasing 2,3-DPG concentrations in red blood cells.
“There is a critical need for novel regimens that elevate the standard of care for patients suffering from sickle cell disease, a burdensome and debilitating disease,” said Sarah Gheuens, M.D., Ph.D., chief medical officer and head of R&D at Agios. “We sincerely thank the patients, study investigators and patient advocates for their instrumental support and partnership in helping us complete enrollment of the Phase 3 RISE UP study. With enrollment now complete, we look forward to completing the trial and sharing topline results with the community in late 2025.”
The Phase 3 RISE UP study enrolled more than 200 patients worldwide. The trial’s primary endpoints are hemoglobin response, defined as a ≥1.0 g/dL increase in average hemoglobin concentration from Week 24 through Week 52 compared with baseline, and annualized rate of sickle cell pain crises. These are important clinical endpoints in sickle cell disease because anemia and pain episodes are the hallmark symptoms of the disease that severely impact a patient’s quality of life.
The positive results from the double-blind period of the RISE UP Phase 2 study, which were presented at the 65th American Society of Hematology (ASH) Annual Meeting & Exposition in December 2023, supported Agios’ further exploration of mitapivat’s risk-benefit profile in sickle cell disease in the Phase 3 study.
About Phase 2/3 RISE UP Study
The RISE UP Phase 2 and 3 studies are evaluating the efficacy and safety of mitapivat in sickle cell disease patients who are 16 years of age or older, have had between two and 10 sickle cell pain crises in the past 12 months, and have hemoglobin within the range of 5.5 to 10.5 g/dL during screening. The Phase 2 and Phase 3 studies are conducted under a single operationally seamless Phase 2/3 protocol. The two studies enrolled different participants and achieved operational efficiency through leveraging the same sites, vendors and other resources.
The Phase 2 study included a 12-week randomized, placebo-controlled period in which participants were randomized in a 1:1:1 ratio to receive 50 mg mitapivat twice daily, 100 mg mitapivat twice daily or matched placebo. The primary endpoints were hemoglobin response, defined as ≥1.0 g/dL increase in average hemoglobin concentration from Week 10 through Week 12 compared to baseline, and safety.
The Phase 3 study includes a 52-week randomized, placebo-controlled period in which participants will be randomized in a 2:1 ratio to receive 100 mg of mitapivat twice daily or matched placebo. The primary endpoints are hemoglobin response, defined as a ≥1.0 g/dL increase in average hemoglobin concentration from Week 24 through Week 52 compared with baseline, and annualized rate of sickle cell pain crises.
Participants who complete the double-blind period of the Phase 2 or Phase 3 studies will have the option to move into a 216-week open-label extension period to receive mitapivat.
About PYRUKYND® (mitapivat)
PYRUKYND is a pyruvate kinase activator indicated for the treatment of hemolytic anemia in adults with pyruvate kinase (PK) deficiency in the United States, and for the treatment of PK deficiency in adult patients in the European Union.
IMPORTANT SAFETY INFORMATION
Acute Hemolysis: Acute hemolysis with subsequent anemia has been observed following abrupt interruption or discontinuation of PYRUKYND in a dose-ranging study. Avoid abruptly discontinuing PYRUKYND. Gradually taper the dose of PYRUKYND to discontinue treatment if possible. When discontinuing treatment, monitor patients for signs of acute hemolysis and anemia including jaundice, scleral icterus, dark urine, dizziness, confusion, fatigue, or shortness of breath.
Adverse Reactions: Serious adverse reactions occurred in
Drug Interactions:
- Strong CYP3A Inhibitors and Inducers: Avoid concomitant use.
- Moderate CYP3A Inhibitors: Do not titrate PYRUKYND beyond 20 mg twice daily.
- Moderate CYP3A Inducers: Consider alternatives that are not moderate inducers. If there are no alternatives, adjust PYRUKYND dosage.
- Sensitive CYP3A, CYP2B6, CYP2C Substrates Including Hormonal Contraceptives: Avoid concomitant use with substrates that have narrow therapeutic index.
- UGT1A1 Substrates: Avoid concomitant use with substrates that have narrow therapeutic index.
- P-gp Substrates: Avoid concomitant use with substrates that have narrow therapeutic index.
Hepatic Impairment: Avoid use of PYRUKYND in patients with moderate and severe hepatic impairment.
Please see full Prescribing Information and Summary of Product Characteristics for PYRUKYND.
About Agios
Agios is the pioneering leader in PK activation and is dedicated to developing and delivering transformative therapies for patients living with rare diseases. In the U.S., Agios markets a first-in-class pyruvate kinase (PK) activator for adults with PK deficiency, the first disease-modifying therapy for this rare, lifelong, debilitating hemolytic anemia. Building on the company's deep scientific expertise in classical hematology and leadership in the field of cellular metabolism and rare hematologic diseases, Agios is advancing a robust clinical pipeline of investigational medicines with programs in alpha- and beta-thalassemia, sickle cell disease, pediatric PK deficiency, myelodysplastic syndrome (MDS)-associated anemia and phenylketonuria (PKU). In addition to its clinical pipeline, Agios is advancing a preclinical TMPRSS6 siRNA as a potential treatment for polycythemia vera. For more information, please visit the company’s website at www.agios.com.
Cautionary Note Regarding Forward-Looking Statements
This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Such forward-looking statements include those regarding the potential benefits of PYRUKYND® (mitapivat); Agios’ plans, strategies and expectations for its preclinical, clinical and commercial advancement of its drug development, including PYRUKYND®; Agios’ strategic vision and goals, including its key milestones for 2024 and 2025; and the potential benefits of Agios’ strategic plans and focus. The words “anticipate,” “expect,” “goal,” “hope,” “milestone,” “plan,” “potential,” “possible,” “strategy,” “will,” “vision,” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Such statements are subject to numerous important factors, risks and uncertainties that may cause actual events or results to differ materially from Agios’ current expectations and beliefs. For example, there can be no guarantee that any product candidate Agios is developing will successfully commence or complete necessary preclinical and clinical development phases, or that development of any of Agios’ product candidates will successfully continue. There can be no guarantee that any positive developments in Agios’ business will result in stock price appreciation. Management's expectations and, therefore, any forward-looking statements in this press release could also be affected by risks and uncertainties relating to a number of other important factors, including, without limitation: risks and uncertainties related to the impact of pandemics or other public health emergencies to Agios’ business, operations, strategy, goals and anticipated milestones, including its ongoing and planned research activities, ability to conduct ongoing and planned clinical trials, clinical supply of current or future drug candidates, commercial supply of current or future approved products, and launching, marketing and selling current or future approved products; Agios’ results of clinical trials and preclinical studies, including subsequent analysis of existing data and new data received from ongoing and future studies; the content and timing of decisions made by the U.S. FDA, the EMA or other regulatory authorities, investigational review boards at clinical trial sites and publication review bodies; Agios’ ability to obtain and maintain requisite regulatory approvals and to enroll patients in its planned clinical trials; unplanned cash requirements and expenditures; competitive factors; Agios' ability to obtain, maintain and enforce patent and other intellectual property protection for any product candidates it is developing; Agios’ ability to establish and maintain key collaborations; uncertainty regarding any milestone or royalty payments related to the sale of its oncology business or its in-licensing of TMPRSS6 siRNA, and the uncertainty of the timing of any such payments; uncertainty of the results and effectiveness of the use of Agios’ cash and cash equivalents; and general economic and market conditions. These and other risks are described in greater detail under the caption "Risk Factors" included in Agios’ public filings with the Securities and Exchange Commission. Any forward-looking statements contained in this press release speak only as of the date hereof, and Agios expressly disclaims any obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise, except as required by law.
Contacts:
Investor Contact
Chris Taylor, VP, Investor Relations and Corporate Communications
Agios Pharmaceuticals
IR@agios.com
Media Contact
Eamonn Nolan, Senior Director, Corporate Communications
Agios Pharmaceuticals
Media@agios.com
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