Agios Pharmaceuticals, Inc. (Agios) operates as a biopharmaceutical company. The company engages solely in the discovery and development of medicines in the field of cellular metabolism. The company accelerates the impact of its portfolio by cultivating connections with patient communities, healthcare professionals, partners and colleagues to discover, develop and deliver potential therapies for rare diseases.
Rare diseases
The lead product candidate in the company’s portfolio, PYRUKYND (mitap...
Agios Pharmaceuticals, Inc. (Agios) operates as a biopharmaceutical company. The company engages solely in the discovery and development of medicines in the field of cellular metabolism. The company accelerates the impact of its portfolio by cultivating connections with patient communities, healthcare professionals, partners and colleagues to discover, develop and deliver potential therapies for rare diseases.
Rare diseases
The lead product candidate in the company’s portfolio, PYRUKYND (mitapivat), is an activator of both wild-type and mutant pyruvate kinase, or PK, enzymes for the potential treatment of hemolytic anemias. PYRUKYND is approved for use by the U.S. Food and Drug Administration, or FDA, for the treatment of hemolytic anemia in adults with PK deficiency in the United States and by the European Commission for the treatment of PK deficiency in adult patients in the European Union, or EU. Additionally, the company received marketing authorization in Great Britain for PYRUKYND for the treatment of PK deficiency in adult patients under the European Commission Decision Reliance Procedure. In December 2024, the company announced that it submitted a supplemental new drug application, or sNDA, to the FDA for PYRUKYND for the treatment of adult patients with non-transfusion dependent and transfusion-dependent alpha- or beta-thalassemia, which was accepted with standard review by the FDA and granted a Prescription Drug User Fee Act, or PDUFA, goal date of September 7, 2025. Also in December 2024, the company announced that it submitted a marketing authorization application, or MAA, to the European Medicines Agency, or EMA, and regulatory applications to the Kingdom of Saudi Arabia and United Arab Emirates health authorities for PYRUKYND for the treatment of adult patients with non-transfusion dependent and transfusion-dependent alpha- or beta-thalassemia.
In addition, the company is evaluating PYRUKYND in Phase 3 clinical trials for the treatment of sickle cell disease, or SCD, and in pediatric patients with PK deficiency. The company is also developing tebapivat, a novel PK activator, for the potential treatment of lower-risk myelodysplastic syndromes, or LR MDS, and hemolytic anemias; G-181, its phenylalanine hydroxylase, or PAH, stabilizer for the potential treatment of phenylketonuria, or PKU; and AG-236, an siRNA in-licensed from Alnylam Pharmaceuticals, Inc., or Alnylam, targeting the transmembrane serine protease 6, or TMPRSS6 gene for the potential treatment of polycythemia vera, or PV.
Strategy
As part of the company’s long-term strategy, it has developed and articulated a strategic vision that delineates its expected evolution in light of its focus on rare diseases.
Development Programs
The company has a proven track record of developing new therapeutic approaches and multiple proprietary first-in-class orally available small molecules.
PYRUKYND (mitapivat): First-in-Class PK Activator
The company is developing PYRUKYND for the treatment of PK deficiency and other hemolytic anemias, such as thalassemia and SCD. PYRUKYND is an orally available small molecule and a potent activator of the wild-type and mutated PK enzymes.
PYRUKYND is approved for use by the FDA for the treatment of hemolytic anemia in adults with PK deficiency in the United States and by the European Commission for the treatment of PK deficiency in adult patients in the EU. Additionally, the company received marketing authorization in Great Britain for PYRUKYND for the treatment of PK deficiency in adult patients under the European Commission Decision Reliance Procedure. In December 2024, the company announced that it submitted an sNDA to the FDA for PYRUKYND for the treatment of adult patients with non-transfusion dependent and transfusion-dependent alpha- or beta-thalassemia, which was accepted with standard review by the FDA and granted a PDUFA goal date of September 7, 2025. Also in December 2024, the company announced that it submitted an MAA to the EMA and regulatory applications to the Kingdom of Saudi Arabia and United Arab Emirates health authorities for PYRUKYND for the treatment of adult patients with non-transfusion dependent and transfusion-dependent alpha- or beta-thalassemia. In addition, the company is evaluating PYRUKYND in clinical trials for the treatment of SCD and in pediatric patients with PK deficiency.
The company has worldwide development and commercial rights to PYRUKYND. In July 2024, the company entered into a distribution agreement with NewBridge Pharmaceuticals FZ-LLC, or the NewBridge Agreement, pursuant to which it granted NewBridge the right to commercialize PYRUKYND in the GCC region.
The company builds its commercial infrastructure to support the commercialization of PYRUKYND in adult PK deficiency in the United States and has expanded this infrastructure to support the potential commercial launch of PYRUKYND in thalassemia in the United States. In connection with the company’s regulatory approvals in the EU and Great Britain, it is providing access to PYRUKYND on a free of charge basis for eligible patients in those jurisdictions through a global managed access program. The company provides access to PYRUKYND for adult patients with PK deficiency in other jurisdictions upon request through the global managed access program, on either a free of charge or for charge basis. The company’s global managed access program has not had a significant impact on its business, financial condition or results of operations. Beyond the global managed access program, the company continues to evaluate options for the commercialization of PYRUKYND outside of the United States, including through exploring potential partnership opportunities, such as the NewBridge Agreement.
The company is evaluating PYRUKYND in numerous clinical trials, including the following:
An extension study evaluating the long-term safety, tolerability and efficacy of treatment with PYRUKYND in patients from ENERGIZE, the company’s completed phase 3, double-blind, randomized, placebo-controlled multicenter study pivotal trial of PYRUKYND in adults with non-transfusion-dependent alpha- or beta-thalassemia. The company announced topline data for ENERGIZE in January 2024 and a more detailed analysis of the data in June 2024. A total of 194 patients were enrolled in the study, with 130 randomized to PYRUKYND 100 mg twice daily, or BID, and 64 randomized to matched placebo. 122 patients (93.8%) in the PYRUKYND arm and 62 patients (96.9%) in the placebo arm completed the 24-week double-blind period of the study.
Based on the results of the ENERGIZE and ENERGIZE-T trials, in December 2024, the company announced that it filed regulatory applications for PYRUKYND for the treatment of adult patients with non-transfusion-dependent, and transfusion-dependent alpha- or beta-thalassemia with the FDA, EMA, and Kingdom of Saudi Arabia, as well as United Arab Emirates health authorities. The company included in its regulatory applications hepatocellular injury as an important potential risk of PYRUKYND in patients with thalassemia and proposed monthly monitoring of liver tests for the first six months of treatment with PYRUKYND. The company updated its PYRUKYND clinical trial protocols across all indications to incorporate monthly monitoring of liver tests for the first six months of treatment, and updated the U.S. Prescribing Information, or USPI, for PYRUKYND for the treatment of hemolytic anemia in adults with PK deficiency to reflect the hepatocellular injury and monitoring.
RISE UP, a phase 2/3 study evaluating the efficacy and safety of PYRUKYND in SCD patients who are 16 years of age or older, have had between two and 10 sickle cell pain crises, or SCPCs, in the past 12 months, and has hemoglobin within the range of 5.5 to 10.5 g/dL during screening. The company enrolled 79 patients in the phase 2 portion of the trial, with 26 patients in the 50 mg twice daily mitapivat arm, 26 patients in the 100 mg twice daily mitapivat arm and 27 patients in the placebo arm. The primary endpoints of the phase 2 portion of the trial were hemoglobin response, defined as = 1 g/dL increase in average hemoglobin concentration from week 10 to week 12 compared to baseline, and safety. In June 2023, the company announced the phase 2 portion of this trial had achieved its primary endpoint of hemoglobin response in patients in both the 50 mg and 100 mg twice daily mitapivat arms. 46.2% of patients (n=12) in the 50 mg twice daily mitapivat arm and 50.0% of patients (n=13) in the 100 mg twice daily mitapivat arm achieved a hemoglobin response, compared to 3.7% of patients (n=1) in the placebo arm (2-sided p=0.0003 and 0.0001, respectively).
In December 2023, the company announced the following additional results of the phase 2 portion of the trial: the least-squares mean (95% confidence interval) for average change from baseline in hemoglobin levels, from week 10 through week 12, for patients in the 50 mg twice daily mitapivat, 100 mg twice daily mitapivat, and placebo arms, respectively, was 1.11 (0.77, 1.45) g/dL, 1.13 (0.79, 1.47) g/dL, and 0.05 (-0.28, 0.39) g/dL; the company observed improvements in annualized rates of SCPCs as the annualized rate of SCPCs (95% confidence interval) for patients in the 50 mg twice daily and 100 mg twice daily mitapivat arms, respectively, was 0.83 (0.34, 1.99) and 0.51 (0.16, 1.59), compared to 1.71 (0.95, 3.08) for patients in the placebo arm; the company observed improvement in patient-reported fatigue scores in the 50 mg twice daily mitapivat arm compared to the placebo arm, and the least-squares mean (95% confidence interval) for average changes from baseline in patient-reported fatigue score, from week 10 through week 12, for patients in the 50 mg twice daily mitapivat, 100 mg twice daily mitapivat, and placebo arms, respectively, was -3.80 (-7.16, -0.45), -0.10 (-3.27, 3.08), and -0.17 (-3.40, 3.07). The safety profile for mitapivat observed in the phase 2 portion of the trial was generally consistent with previously reported data in other studies of SCD and other hemolytic anemias. The most common TEAEs in the 50 mg BID, 100 mg BID, and placebo arms, respectively, were: headache (n=6, 6, 7), arthralgia (n=3, 5, 9), dysmenorrhea (n=0, 3, 0), pain (n=3, 3, 2), pain in extremity (n=1, 3, 6), back pain (n=4, 2, 3), nausea (n=1, 2, 4), fatigue (n=4, 1, 5), and influenza-like illness (n=1, 1, 3). There were no serious TEAEs attributed to mitapivat and there were no AEs leading to drug reduction, discontinuation, interruption or death in either the mitapivat or the placebo arms. Of the 79 patients enrolled in the study, 73 continued into the Phase 2 open-label extension period. In October 2023, the company enrolled the first patient in the phase 3 portion of this trial, and it has since enrolled over 200 patients worldwide. The phase 3 portion includes a 52-week randomized, placebo-controlled period in which participants will be randomized in a 2:1 ratio to receive the recommended (100 mg twice daily) PYRUKYND dose level or the placebo. The primary endpoints are hemoglobin response, defined as =1 g/dL increase in average hemoglobin from week 24 through week 52 compared to baseline, and annualized rate of SCPCs. The secondary endpoints include additional clinical efficacy measures related to anemia, hemolysis, erythropoiesis, patient-reported fatigue and pain, annualized frequency of hospitalizations for SCPCs, and change from baseline in six-minute walk test. Participants who complete either the phase 2 or phase 3 portion will have the option to move into a 216-week open-label extension period to continue to receive PYRUKYND. The company has completed enrollment and expect to announce topline data for this trial in late 2025, with a potential U.S. commercial launch in 2026, if approved.
ACTIVATE-kids and ACTIVATE-kidsT, double-blind phase 3 studies evaluating the efficacy and safety of PYRUKYND as a potential treatment for PK deficiency in not regularly transfused and regularly transfused patients between one and 18 years old. The company announced topline data for ACTIVATE-kidsT in August 2024. The company announced topline data for ACTIVATE-kids in February 2025.
An extension study evaluating the long-term safety, tolerability and efficacy of treatment with PYRUKYND in patients from ACTIVATE and ACTIVATE-T, the company’s completed pivotal trials of PYRUKYND in not regularly transfused and regularly transfused adult patients with PK deficiency.
An extension study evaluating the long-term safety, tolerability and efficacy of treatment with PYRUKYND in patients from DRIVE PK, the company’s completed global phase 2, first-in-patient, open-label safety and efficacy clinical trial of PYRUKYND in adult, not regularly transfused patients with PK deficiency.
Tebapivat: Novel PK Activator
The company is developing tebapivat, a novel PK activator for the potential treatment of LR MDS and hemolytic anemias. Tebapivat has been granted orphan drug designation for the treatment of MDS by the FDA.
The company has completed a phase 1 clinical trial evaluating tebapivat in healthy volunteers and patients with SCD, and it expects to dose the first patient in a phase 2 clinical trial of tebapivat in adult patients with SCD in mid-2025.
The company also initiated a phase 2a clinical trial of tebapivat in adults with LR MDS in the third quarter of 2022, and the trial has completed enrollment with 22 patients, including 12 patients classified as non-transfused and 10 patients classified as low transfusion burden. Patients received 5 mg of tebapivat once daily for up to 16 weeks. The two primary endpoints of the trial were transfusion independence (for patients classified as low transfusion burden), defined as transfusion-free for = eight consecutive weeks during the 16-week treatment period, and hemoglobin response, defined as a = 1.5 g/dL increase from baseline in the average hemoglobin concentration measured from week 8 through week 16.
In November 2023, the company announced that it achieved clinical proof-of-concept in the phase 2a portion of the trial. The company observed that four of the 10 patients with low transfusion burden achieved the transfusion independence endpoint, and one of the 22 patients achieved the hemoglobin response endpoint in the 16-week treatment period. The safety profile observed was consistent with data reported in the healthy volunteer study of tebapivat. 19 patients elected to enroll in the extension period for up to 156 weeks. The company evaluated the phase 2a trial results and assessed the impact of those results on the phase 2b portion of the protocol and based on the data generated in the phase 2a portion of the trial, it plans to increase the dosage levels evaluated in the phase 2b portion of the trial, which the company initiated in the third quarter of 2024. The company expects to complete enrollment in this phase 2b trial in late 2025.
Other Programs
In addition to the development programs, the company is developing AG-181, a PAH stabilizer for the potential treatment of PKU, for which it filed an IND in December 2023. The company initiated a phase 1 clinical trial of AG-181 in healthy volunteers in the first quarter of 2024. Also, in July 2023, the company entered into a license agreement with Alnylam for the development and commercialization of products containing, or consisting of, an siRNA preclinical development candidate discovered by Alnylam and targeting the TMPRSS6 gene. Furthermore, the company has begun preclinical development of a product candidate, AG-236, for the potential treatment of patients with PV.
Intellectual Property
PK Activator Program
The patent portfolio for the company’s PK activator program contains issued patents and pending patent applications directed to compositions of matter for PYRUKYND, as well as to related compounds, various solid-state forms of PYRUKYND, compositions of matter for additional PKR activators, such as tebapivat, as well as various solid-state forms, methods of use and methods of manufacture for tebapivat and other novel compounds. As of February 1, 2025, the company owned 17 issued United States patents and 434 issued foreign patents and has pending patent applications in the United States and in various foreign jurisdictions. The patents that have issued or may issue for PYRUKYND will have a statutory expiration date of at least 2030 to 2042, and the patents that have issued or may issue for tebapivat will have a statutory expiration date of at least 2038 to 2045. The company has issued patents and pending patent applications pertaining to its products/product candidates in its PK activator program in a number of foreign jurisdictions, including Argentina, Australia, Austria, Belgium, Brazil, Canada, China, the Czech Republic, Denmark, Finland, France, Germany, Greece, Hungary, Ireland, Italy, Japan, Lebanon, Lithuania, Mexico, the Netherlands, Norway, Poland, Portugal, Romania, Russia, Saudi Arabia, Slovakia, Slovenia, Spain, Sweden, Switzerland, Taiwan, Turkey, and the United Kingdom. Two of the European patents in the company’s PYRUKYND portfolio, neither being the primary compound patent, has been challenged in opposition proceedings.
PAH Stabilizer Program
As of February 1, 2025, the company owned one issued United States patent and two issued foreign patents and have pending patent applications in the United States and in various foreign jurisdictions. The patents that have issued or may issue for the company’s PAH stabilizer program will have a statutory expiration date of at least 2043 to 2044. The company has issued patents and pending patent applications pertaining to its products/product candidates in the company’s PAH stabilizer program in a number of foreign jurisdictions, including Argentina, Australia, Brazil, Canada, China, Europe, Japan, Lebanon, Mexico, Eurasia, Saudi Arabia, and Taiwan.
Competition
The company’s competitors include but are not limited to: BioMarin Pharmaceutical, Inc., or BioMarin; bluebird bio, Inc., or bluebird; Bristol-Myers Squibb Company, or BMS; CRISPR Therapeutics AG, or CRISPR; Emmaus Life Sciences, Inc., or Emmaus; Fulcrum Therapeutics, Inc., or Fulcrum; Geron Corporation, or Geron; Incyte Corporation, or Incyte; Ionis Pharmaceuticals, Inc., or Ionis; Merck & Co., Inc., or Merck; Novartis International AG, or Novartis; Novo Nordisk A/S, or Novo; Otsuka Pharmaceutical Co., Ltd., or Otsuka; Pfizer, Inc., or Pfizer; PharmaEssentia USA Corporation, or PharmaEssentia; Protagonist Therapeutics, Inc., or Protagonist, in collaboration with Takeda, Pharmaceutical Company Limited, or Takeda; PTC Therapeutics, Inc., or PTC; Rocket Pharmaceuticals, Inc., or Rocket Pharma; Silence Therapeutics plc, or Silence; Takeda; and Vertex Pharmaceuticals Incorporated, or Vertex.
Research and Development
Cash used in operating activities of $389.8 million during the year ended December 31, 2024, of which all was used by continuing operations, was primarily due to operating expenses driven by research and development costs of the company.
History
Agios Pharmaceuticals, Inc. was incorporated in 2007.
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