FDA Approves Pyrukynd (mitapivat) as First Disease-Modifying Therapy for Hemolytic Anemia in Adults with Pyruvate Kinase Deficiency


Pyrukynd (mitapivat)


CAMBRIDGE, Mass., Feb. 17, 2022 (GLOBE NEWSWIRE) -- Agios Pharmaceuticals, Inc. (NASDAQ: AGIO), a leader in the field of cellular metabolism pioneering therapies for genetically defined diseases, today announced that the U.S. Food and Drug Administration (FDA) has approved Pyrukynd® (mitapivat) in the U.S. for the treatment of hemolytic anemia in adults with pyruvate kinase (PK) deficiency, a rare, debilitating, lifelong hemolytic anemia. Pyrukynd® is a first-in-class, oral PK activator and the first approved disease-modifying therapy for this disease.

“The successful ACTIVATE and ACTIVATE-T studies demonstrate the impact of mitapivat in significantly improving hemolysis and anemia in PK deficiency,” said Hanny Al-Samkari, M.D., hematologist and clinical investigator at the Mass General Cancer Center and Harvard Medical School, and an investigator in these pivotal Phase 3 studies. “The FDA approval of mitapivat, a targeted agent and first disease-modifying medication in PK deficiency, is an encouraging step forward for these patients that addresses a significant unmet need.”

“Pyrukynd® is the first approved therapy for PK deficiency and marks an important milestone for these patients, who may face tremendous challenges and debilitating symptoms throughout the course of this lifelong disease,” said Rachael Grace, M.D., MMSc, pediatric hematologist, director of hematology clinical research at Boston Children’s Hospital and an investigator in the Phase 2 DRIVE PK and Phase 3 ACTIVATE studies. “Partnering with Agios and the PK deficiency community to improve understanding of the natural history of this rare disease and bring a new medicine to patients has been an honor, and I look forward to additional collaboration in the future.”

“I am so grateful that Pyrukynd® has been approved for PK deficiency. As both patient and caregiver, I spent the majority of my life feeling alone in this disease and never thought I would see a medicine approved,” said Kim Hall, who was diagnosed with PK deficiency in 1969 and is the mother of two adult daughters living with PK deficiency. All three women participated in the Phase 3 Pyrukynd® PK deficiency clinical program. “The experience of being part of the clinical trials has been impactful because of the connections we have built with other patients, healthcare providers and Agios colleagues who understand PK deficiency and are actively working to improve patients’ lives.”

“For more than a decade, we have been pioneering the science of PK activation in order to bring Pyrukynd® to people with PK deficiency and provide them with the first medication approved specifically to address this rare, debilitating blood disorder,” said Jackie Fouse, Ph.D., chief executive officer at Agios. “We remain committed to partnering with patients, caregivers, advocates and healthcare providers to ensure that the impact of Pyrukynd® is maximized through robust support, education and access programs. These connections have fueled today’s tremendous milestone for the PK deficiency community. Each of us at Agios is dedicated to making a difference for people with PK deficiency, as well as to expanding the reach of Pyrukynd® and our clinical and research programs to many more patients with genetically defined diseases around the world.”

Agios is offering a robust set of access programs aimed at reducing or eliminating patient out-of-pocket costs for Pyrukynd®, including a copay program that lowers copays to $0 for eligible commercially-insured patients and a Patient Assistance Program (PAP) that offers free prescriptions to eligible uninsured and underinsured patients. The myAgios® patient support services program provides a centralized resource to assist with support, access, education and adherence. Learn more and enroll at www.myagios.com.

Pyrukynd® is expected to be available in the U.S. approximately two weeks after approval. Pyrukynd® was reviewed by the FDA under Priority Review and was previously granted orphan drug designation. Pyrukynd® is also under review by the European Medicines Agency (EMA) as a potential treatment for adults with PK deficiency, and Agios expects a regulatory decision in the EU by the end of 2022. Learn more at www.PYRUKYND.com.

Pyrukynd® Safety and Efficacy Data

The FDA granted approval to Pyrukynd® based on results from two pivotal studies, ACTIVATE and ACTIVATE-T, conducted in not regularly transfused and regularly transfused adults with PK deficiency, respectively.

  • The Phase 3 ACTIVATE trial of mitapivat achieved its primary endpoint. Pyrukynd® demonstrated a statistically significant increase in hemoglobin in patients with PK deficiency who are not regularly transfused.
    • 40 percent (n=16) of patients randomized to v® achieved a hemoglobin response, compared to 0 patients randomized to placebo (2-sided p<0.0001).
    • Statistically significant improvements compared to placebo were also demonstrated for all pre-specified secondary endpoints, including markers of hemolysis and ineffective erythropoiesis.
    • Patients treated with Pyrukynd® experienced changes in jaundice (difference in LS Mean of Pyrukynd® minus placebo: -0.4), tiredness (difference in LS Mean of Pyrukynd® minus placebo: -1.1) and shortness of breath (difference in LS Mean of Pyrukynd® minus placebo: -0.3), as assessed with the daily Pyruvate Kinase Deficiency Diary (PKDD) where lower scores represent less sign/symptom severity.
    • Serious adverse reactions occurred in 10 percent (n=4) of patients receiving Pyrukynd®, including atrial fibrillation, gastroenteritis, rib fracture and musculoskeletal pain, which each occurred in 1 patient.
    • The most common adverse reactions including laboratory abnormalities (≥ 10%) in patients with PK deficiency were estrone decreased (males), increased urate, back pain, estradiol decreased (males) and arthralgia.
  • The Phase 3 ACTIVATE-T trial of mitapivat achieved its primary endpoint. Mitapivat demonstrated a statistically significant and clinically meaningful reduction in transfusion burden for patients who are regularly transfused.
    • 33 percent (n=9) of patients achieved a transfusion reduction response, defined as a ≥33% reduction in transfusion burden in the 24-week fixed dose period compared with individual historical transfusion burden standardized to 24 weeks.
    • 22 percent (n=6) of patients were transfusion-free during the fixed-dose period.
    • The adverse reactions reported in the ACTIVATE-T study were consistent with those observed in ACTIVATE.

A full analysis of these data was presented at the 2021 European Hematology Association (EHA) Virtual Congress. An extension study for adults with PK deficiency previously enrolled in ACTIVATE or ACTIVATE-T is ongoing and designed to evaluate the long-term safety, tolerability and efficacy of treatment with mitapivat; initial results from the extension study were recently presented at the 2021 American Society of Hematology (ASH) Annual Meeting and Exposition.

In mid-2022, the company expects to initiate two pivotal studies – ACTIVATE-kids and ACTIVATE-kidsT – in pediatric patients with PK deficiency who are not regularly transfused and who are regularly transfused, respectively. Agios also continues to advance its Phase 3 ENERGIZE and ENERGIZE-T studies in not regularly transfused and regularly transfused adults with thalassemia, as well as its Phase 2/3 RISE UP study in sickle cell disease.

About PK Deficiency

Pyruvate kinase (PK) deficiency is a rare, inherited disease that presents as chronic hemolytic anemia, which is the accelerated destruction of red blood cells. The inherited mutation in the PKLR gene can cause a deficit in energy within the red blood cell, as evidenced by lower PK enzyme activity, a decline in adenosine triphosphate (ATP) levels and a build-up of upstream metabolites, including 2,3-DPG (2,3-diphosphoglycerate).

PK deficiency is associated with serious complications, including gallstones, pulmonary hypertension, extramedullary hematopoiesis, osteoporosis and iron overload and its sequelae, which can occur regardless of the degree of anemia or transfusion burden. PK deficiency can also cause quality of life problems, including challenges with work and school activities, social life and emotional health. Current management strategies for PK deficiency, including red blood cell transfusions and splenectomy, are associated with both short- and long-term risks. For more information, please visit the websites of two U.S.-based independent patient advocacy groups dedicated to PK deficiency: PK Deficiency Foundation and Thrive with PK Deficiency.

myAgios® Patient Support Services

The myAgios® patient support services program is a centralized platform for people living with PK deficiency and their caregivers. After enrolling in the program, patients and caregivers are connected with a dedicated Patient Support Manager (PSM) with a clinical background to provide tailored support, educational resources, access and benefits investigation services, financial assistance programs, prescription fulfillment and opportunities to connect with other patients and caregivers in the community. To learn more or enroll, please visit www.myagios.com.

 About Pyrukynd® (mitapivat) 

Pyrukynd is a pyruvate kinase activator indicated for the treatment of hemolytic anemia in adults with pyruvate kinase (PK) deficiency.


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 10% of patients receiving Pyrukynd in the ACTIVATE trial, including atrial fibrillation, gastroenteritis, rib fracture, and musculoskeletal pain, each of which occurred in 1 patient. In the ACTIVATE trial, the most common adverse reactions including laboratory abnormalities (≥10%) in patients with PK deficiency were estrone decreased (males), increased urate, back pain, estradiol decreased (males), and arthralgia.

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.

About Agios

Agios is a biopharmaceutical company that is fueled by connections. The Agios team cultivates strong bonds with patient communities, healthcare professionals, partners and colleagues to discover, develop and deliver therapies for genetically defined 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 leadership in the field of cellular metabolism, Agios is advancing a robust clinical pipeline of investigational medicines with active and planned programs in alpha- and beta-thalassemia, sickle cell disease, pediatric PK deficiency and MDS-associated anemia. In addition to its clinical pipeline, Agios has multiple investigational therapies in preclinical development and an industry-leading research team with unmatched expertise in cellular metabolism and genetics. For more information, please visit the company’s website at www.agios.com.

Source: Agios Pharmaceuticals, Inc.

Posted: February 2022

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