Agios’ Phase 3 ACTIVATE-Kids Study of Mitapivat in Children with Pyruvate Kinase (PK) Deficiency Not Regularly Transfused Met Primary Endpoint
Agios Pharmaceuticals (AGIO) announced positive results from its Phase 3 ACTIVATE-Kids study of mitapivat in children with Pyruvate Kinase (PK) deficiency. The study met its primary endpoint of hemoglobin response in non-regularly transfused patients aged 1 to <18 years.
The trial enrolled 30 patients, with 19 receiving mitapivat and 11 receiving placebo. 31.6% (6/19) of patients in the mitapivat arm achieved hemoglobin response compared to 0% in the placebo arm. The safety profile was consistent with previous adult studies, with no treatment discontinuations due to adverse events.
This marks Agios' first pediatric clinical program for rare hemolytic anemia, following the previously reported positive results from ACTIVATE-KidsT study in regularly transfused children. Based on these results, Agios plans to submit a marketing application for mitapivat in pediatric PK deficiency patients.
Agios Pharmaceuticals (AGIO) ha annunciato risultati positivi dal suo studio di Fase 3 ACTIVATE-Kids su mitapivat in bambini con carenza di Piruvato Chinasi (PK). Lo studio ha raggiunto il suo obiettivo primario di risposta dell'emoglobina in pazienti non sottoposti a trasfusioni regolari di età compresa tra 1 e <18 anni.
Il trial ha arruolato 30 pazienti, di cui 19 hanno ricevuto mitapivat e 11 un placebo. Il 31,6% (6/19) dei pazienti nel gruppo mitapivat ha ottenuto una risposta dell'emoglobina rispetto allo 0% nel gruppo placebo. Il profilo di sicurezza è stato coerente con studi precedenti su adulti, senza interruzioni del trattamento a causa di eventi avversi.
Questo segna il primo programma clinico pediatrico di Agios per l'anemia emolitica rara, dopo i risultati positivi precedentemente riportati dallo studio ACTIVATE-KidsT in bambini sottoposti a trasfusioni regolari. Sulla base di questi risultati, Agios prevede di presentare una domanda di commercializzazione per mitapivat in pazienti pediatrici con carenza di PK.
Agios Pharmaceuticals (AGIO) anunció resultados positivos de su estudio de Fase 3 ACTIVATE-Kids sobre mitapivat en niños con deficiencia de Piruvato Quinasa (PK). El estudio alcanzó su objetivo primario de respuesta de hemoglobina en pacientes no transfundidos regularmente de entre 1 y <18 años.
El ensayo incluyó a 30 pacientes, de los cuales 19 recibieron mitapivat y 11 un placebo. El 31.6% (6/19) de los pacientes en el grupo de mitapivat logró una respuesta de hemoglobina en comparación con el 0% en el grupo placebo. El perfil de seguridad fue consistente con estudios anteriores en adultos, sin interrupciones del tratamiento debido a eventos adversos.
Este es el primer programa clínico pediátrico de Agios para anemia hemolítica rara, tras los resultados positivos previamente reportados del estudio ACTIVATE-KidsT en niños que reciben transfusiones regularmente. Con base en estos resultados, Agios planea presentar una solicitud de comercialización para mitapivat en pacientes pediátricos con deficiencia de PK.
Agios Pharmaceuticals (AGIO)는 피루vate 키나제(PK) 결핍 아동을 대상으로 한 mitapivat의 3상 ACTIVATE-Kids 연구에서 긍정적인 결과를 발표했습니다. 이 연구는 1세에서 <18세 사이의 비정기적으로 수혈된 환자에서 헤모글로빈 반응의 주요 목표를 달성했습니다.
시험에는 30명의 환자가 등록되었으며, 19명이 mitapivat을, 11명이 위약을 받았습니다. 31.6% (6/19)의 mitapivat 그룹 환자가 위약 그룹의 0%에 비해 헤모글로빈 반응을 달성했습니다. 안전성 프로필은 이전 성인 연구와 일치했으며, 부작용으로 인한 치료 중단은 없었습니다.
이는 Agios의 드문 용혈성 빈혈에 대한 첫 번째 소아 임상 프로그램으로, 정기적으로 수혈받는 아동을 대상으로 한 ACTIVATE-KidsT 연구에서 이전에 보고된 긍정적인 결과에 이어 발표되었습니다. 이러한 결과를 바탕으로 Agios는 PK 결핍 아동을 위한 mitapivat의 마케팅 신청서를 제출할 계획입니다.
Agios Pharmaceuticals (AGIO) a annoncé des résultats positifs de son étude de Phase 3 ACTIVATE-Kids sur le mitapivat chez les enfants atteints d'une déficience en pyruvate kinase (PK). L'étude a atteint son objectif principal de réponse en hémoglobine chez des patients non transfusés régulièrement âgés de 1 à <18 ans.
L'essai a inclus 30 patients, dont 19 ont reçu du mitapivat et 11 un placebo. 31,6% (6/19) des patients dans le groupe mitapivat ont atteint une réponse en hémoglobine contre 0% dans le groupe placebo. Le profil de sécurité était cohérent avec les études précédentes chez les adultes, sans interruption du traitement en raison d'événements indésirables.
Ceci marque le premier programme clinique pédiatrique d'Agios pour l'anémie hémolytique rare, suite aux résultats positifs précédemment rapportés de l'étude ACTIVATE-KidsT chez des enfants transfusés régulièrement. Sur la base de ces résultats, Agios prévoit de soumettre une demande de commercialisation pour le mitapivat chez les patients pédiatriques atteints de déficience en PK.
Agios Pharmaceuticals (AGIO) hat positive Ergebnisse aus seiner Phase-3-Studie ACTIVATE-Kids zu Mitapivat bei Kindern mit Pyruvatkinase (PK)-Mangel bekannt gegeben. Die Studie erreichte ihr primäres Ziel der Hämoglobinreaktion bei nicht regelmäßig transfundierten Patienten im Alter von 1 bis <18 Jahren.
In der Studie wurden 30 Patienten eingeschlossen, von denen 19 Mitapivat erhielten und 11 ein Placebo. 31,6% (6/19) der Patienten in der Mitapivat-Gruppe erreichten eine Hämoglobinreaktion im Vergleich zu 0% in der Placebo-Gruppe. Das Sicherheitsprofil war konsistent mit früheren Studien an Erwachsenen, ohne Unterbrechungen der Behandlung aufgrund von Nebenwirkungen.
Dies markiert das erste pädiatrische klinische Programm von Agios für seltene hämolytische Anämie, nachdem zuvor positive Ergebnisse aus der ACTIVATE-KidsT-Studie bei regelmäßig transfundierten Kindern berichtet wurden. Basierend auf diesen Ergebnissen plant Agios, einen Zulassungsantrag für Mitapivat bei pädiatrischen PK-Mangel-Patienten einzureichen.
- Phase 3 ACTIVATE-Kids trial met primary endpoint
- 31.6% of treated patients achieved hemoglobin response vs 0% for placebo
- All patients completed the 20-week double-blind period
- No treatment discontinuations due to adverse events
- Company plans to submit marketing application based on results
- Only 6 out of 19 patients responded to treatment
Insights
The successful completion of the ACTIVATE-Kids Phase 3 trial represents a significant breakthrough in rare disease treatment. The study's robust design, utilizing Bayesian statistical methodology and achieving statistical significance across all borrowing weights, demonstrates exceptional scientific rigor. The 31.6% response rate in the mitapivat arm versus 0% in placebo, coupled with improvements in hemolysis markers, provides compelling evidence of clinical efficacy.
The trial's success has multiple strategic implications. First, it establishes mitapivat as the first potential oral therapy for pediatric PK deficiency, addressing an urgent unmet medical need. Second, the consistent safety profile between pediatric and adult populations significantly de-risks the regulatory pathway. The completion of both ACTIVATE-Kids and ACTIVATE-KidsT trials positions Agios to potentially expand its addressable market to include both transfusion-dependent and non-dependent pediatric patients.
Looking ahead, this success has broader implications for Agios' pipeline development in thalassemia and sickle cell disease pediatric programs. The demonstrated ability to successfully conduct pediatric rare disease trials enhances the company's credibility in this challenging space. The positive results in both transfused and non-transfused populations suggest potential applicability across various hemolytic anemias, possibly expanding the total addressable market significantly.
The perfect retention rate during the trial period (no discontinuations) is particularly noteworthy in pediatric studies and suggests excellent tolerability, which could translate into strong real-world adoption. This positions Agios favorably for upcoming regulatory submissions and potential commercialization in the pediatric segment.
– ACTIVATE-Kids is the First Study to Demonstrate Efficacy of an Oral Therapy for Children with PK Deficiency Who Are Not Regularly Transfused –
– Safety Results Consistent with Safety Profile for Mitapivat Previously Observed in Adults with PK Deficiency Who Are Not Regularly Transfused –
– First Mitapivat Pediatric Clinical Program for a Rare Hemolytic Anemia; Double-blind Period Completed for Both PK Deficiency Trials ACTIVATE-Kids and ACTIVATE-KidsT –
CAMBRIDGE, Mass., Feb. 13, 2025 (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 the ACTIVATE-Kids Phase 3 study of mitapivat in children aged 1 to <18 years with PK deficiency who are not regularly transfused achieved its primary endpoint of hemoglobin response. In the ACTIVATE-Kids 20-week double-blind treatment period, the safety results were consistent with the safety profile for mitapivat previously observed for adult patients with PK deficiency who are not regularly transfused. In August 2024, Agios also reported topline results from the ACTIVATE-KidsT Phase 3 study of mitapivat in children aged 1 to <18 years with PK deficiency who are regularly transfused.
“The positive results for the ACTIVATE-Kids Phase 3 trial represent a very important step forward for the PK deficiency community, building on the clinical benefits demonstrated by mitapivat in adults with PK deficiency. The ACTIVATE-Kids and ACTIVATE-KidsT Phase 3 studies mark Agios’ first pediatric clinical program for a rare hemolytic anemia, providing valuable insights that will help shape the company’s future clinical programs evaluating mitapivat in pediatric patients with thalassemia and sickle cell disease,” said Sarah Gheuens, M.D., Ph.D., chief medical officer and head of R&D at Agios. “We are deeply grateful to all who are contributing to the ACTIVATE-Kids and ACTIVATE-KidsT trials, especially the children who are participating in the studies and their caregivers. With data now available from the randomized, placebo-controlled, double-blind period of both Phase 3 pediatric PK deficiency studies, we look forward to sharing more detailed findings with the community and interacting with regulators.”
Topline results for the Phase 3 ACTIVATE-Kids trial were as follows:
- A total of 30 patients aged 1 to <18 years were enrolled in the study, with 19 randomized to mitapivat twice-daily and 11 randomized to matched placebo.
- The primary endpoint of the study was hemoglobin response, defined as a ≥1.5 g/dL increase in hemoglobin concentration from baseline that is sustained at two or more scheduled assessments at Weeks 12, 16, and 20 during the double-blind period.
- The analysis of the primary endpoint was based on Bayesian statistical methodology whereby the hemoglobin response data from the adult ACTIVATE study inform and contribute to the analysis of hemoglobin response in the ACTIVATE-Kids study. The analysis was performed using a range of relative borrowing from the adult ACTIVATE study, representing the prior degree of belief in the similarity of the treatment effect in the pediatric and adult populations. The pre-specified statistical criterion for the primary endpoint in ACTIVATE-Kids was met for all possible borrowing weights (ranging from 0 to 1).
- In addition, the pre-specified supportive analysis based on traditional methodology comparing the hemoglobin response rate for mitapivat versus placebo, provided further evidence that the primary endpoint was met. There were
31.6% (6/19) of patients in the mitapivat arm achieving a hemoglobin response compared to0% (0/11) of patients in the placebo arm; the95% confidence interval for the difference in hemoglobin response rates between mitapivat and placebo was >0 (95% CI=10.8% to52.7% ).
- In addition, improvements in changes from baseline for markers of hemolysis (indirect bilirubin, lactate dehydrogenase and haptoglobin) were observed in the mitapivat arm compared to the placebo arm.
- All patients in both treatment arms completed the 20-week double-blind period of the study.
- In the 20-week double-blind period of the study, a similar proportion of patients had adverse events (AEs) in the mitapivat and placebo arms and there were no discontinuations of study treatment due to AEs or for any reason.
“PK deficiency can lead to debilitating fatigue and a range of serious complications and symptoms, severely affecting and disrupting a child’s quality of life,” said Rachael F. Grace, M.D., MMSc; Dana-Farber/Boston Children’s Cancer and Blood Disorder Center, Harvard Medical School, Boston, an investigator in the ACTIVATE-Kids study. “The efficacy and safety results from the ACTIVATE-Kids and ACTIVATE-KidsT Phase 3 studies demonstrate the potential for clinically meaningful benefits with mitapivat in children with PK deficiency who are and are not regularly transfused, improving anemia and reducing the need for transfusions.”
Based on the clinically meaningful results observed in both the ACTIVATE-Kids and ACTIVATE-KidsT Phase 3 studies, Agios intends to submit a marketing application for mitapivat in pediatric patients with PK deficiency. The company also plans to present more detailed analyses from both studies at upcoming medical conferences.
About PYRUKYND® (mitapivat)
U.S. INDICATION
PYRUKYND is a pyruvate kinase activator indicated for the treatment of hemolytic anemia in adults with pyruvate kinase (PK) deficiency.
U.S. 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.
Hepatocellular Injury in Another Condition: In patients with another condition treated with PYRUKYND at a higher dose than that recommended for patients with PK deficiency, liver injury has been observed. These events were characterized by a time to onset within the first 6 months of treatment with peak elevations of alanine aminotransferase of >5× upper limit of normal (ULN) with or without jaundice. All patients discontinued treatment with PYRUKYND, and these events improved upon treatment discontinuation.
Obtain liver tests prior to the initiation of PYRUKYND and monthly thereafter for the first 6 months and as clinically indicated. Interrupt PYRUKYND if clinically significant increases in liver tests are observed or alanine aminotransferase is >5x ULN. Discontinue PYRUKYND if hepatic injury due to PYRUKYND is suspected.
Adverse Reactions: The most common adverse reactions including laboratory abnormalities (≥
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 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); 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 royalty payments related to the sale of its oncology business or any milestone or royalty payments related to its in-licensing of AG-236, 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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