Core Insights - Agios Pharmaceuticals has received FDA approval for AQVESME™ (mitapivat), the first oral pyruvate kinase activator for treating anemia in adults with alpha- or beta-thalassemia, making it the only FDA-approved treatment for both non-transfusion-dependent and transfusion-dependent forms of the disease [1][3][4] Group 1: FDA Approval and Clinical Trials - The FDA approval is based on the results from the ENERGIZE and ENERGIZE-T Phase 3 trials, which included 452 patients and demonstrated significant improvements in hemolytic anemia, hemoglobin levels, and fatigue compared to placebo [2][9][10] - The ENERGIZE trial involved 194 non-transfusion-dependent patients, while the ENERGIZE-T trial included 258 transfusion-dependent patients, both showing positive efficacy endpoints [10][11] Group 2: Impact on Thalassemia Community - The approval of AQVESME is seen as a landmark moment for the thalassemia community, providing a new treatment option for approximately 6,000 adult patients in the U.S. who suffer from this debilitating disease [2][8] - The introduction of AQVESME is expected to address the urgent needs of patients, particularly in reducing the need for regular blood transfusions and improving quality of life [3][4] Group 3: Safety and Risk Management - Due to the risk of hepatocellular injury, AQVESME will be available only through a Risk Evaluation and Mitigation Strategy (REMS) program, which includes regular liver function tests and education for patients and healthcare providers [14][15][18] - In clinical trials, 5 patients experienced adverse reactions suggestive of hepatocellular injury, with 2 requiring hospitalization, highlighting the importance of monitoring liver health during treatment [17][19] Group 4: Market Availability - AQVESME is expected to be available in the U.S. by late January 2026, following the implementation of the REMS program [4][5] - The drug will be marketed under the AQVESME brand name for thalassemia, while continuing to be marketed as PYRUKYND® for PK deficiency, which does not require a REMS program [4][5]

Core Insights - Agios Pharmaceuticals announced topline results from the RISE UP Phase 3 trial of mitapivat, an oral pyruvate kinase activator, for patients with sickle cell disease, demonstrating significant improvements in hemoglobin response and hemolysis markers [1][5][6] Trial Results - The trial met its primary endpoint of hemoglobin response, with 40.6% of patients in the mitapivat arm achieving a significant increase in hemoglobin levels compared to 2.9% in the placebo group [12] - Mitapivat showed a statistically significant improvement in average hemoglobin concentration and indirect bilirubin levels, but the reduction in annualized rate of sickle cell pain crises did not achieve statistical significance [2][3][12] - The safety profile of mitapivat was consistent with previous trials, with a similar proportion of adverse events reported in both mitapivat and placebo groups [19] Patient Outcomes - Patients who achieved hemoglobin response experienced clinically meaningful benefits in the annualized rate of sickle cell pain crises and hospitalizations, as well as improvements in fatigue scores [4][12][13] - The average change in PROMIS Fatigue score was -5.19 for hemoglobin responders, indicating a clinically meaningful improvement [13] Regulatory and Future Plans - Agios plans to engage with the FDA to discuss the findings and intends to submit a marketing application for mitapivat for sickle cell disease in early 2026 [15][16] - The company is also focused on the potential U.S. approval of PYRUKYND for thalassemia, anticipated in December 2025, and will take steps to reduce operating expenses [16] About Sickle Cell Disease - Sickle cell disease is a rare inherited blood disorder characterized by abnormal hemoglobin production, leading to severe complications and increased healthcare needs [18]

Core Insights - Agios Pharmaceuticals is set to present new data on mitapivat, an oral pyruvate kinase activator, at the 67th American Society of Hematology Annual Meeting in December 2025, highlighting its potential for treating rare blood disorders [1][2]. Group 1: Presentation Highlights - The presentations will showcase clinical and preclinical data supporting mitapivat's therapeutic potential for thalassemia, sickle cell disease, and pyruvate kinase deficiency, which are rare and life-threatening blood disorders [2]. - A total of 10 presentations and publications will be shared at ASH 2025, including significant findings from the ENERGIZE-T Phase 3 trial and other studies [3][5]. Group 2: ENERGIZE-T Trial Results - In the ENERGIZE-T trial, 77.8% of patients with alpha-thalassemia in the mitapivat arm achieved the primary endpoint of transfusion reduction, compared to 0% in the placebo arm [5]. - Long-term results showed that patients who achieved transfusion independence had a mean duration of 30.5 weeks without transfusions, with a maximum of 84.3 weeks [5]. Group 3: Pediatric and Preclinical Findings - The ACTIVATE-Kids Phase 3 trial demonstrated a higher hemoglobin response rate in children with pyruvate kinase deficiency treated with mitapivat compared to the placebo group [5]. - Preclinical data indicated that mitapivat protects against cardiomyopathy in a mouse model of beta-thalassemia, potentially linked to its activation of the PKM2 isoform [5]. Group 4: Advisory Council Research - Research from Agios-supported advisory councils revealed key knowledge gaps about thalassemia and the impact of fatigue on patients with rare blood disorders [5]. - A global patient survey identified the importance of regular monitoring in non-transfusion-dependent patients and highlighted cognitive impairment as a significant issue related to fatigue [5].

Financial Performance - Q3 2025 net revenues reached $12.9 million, a 44% increase compared to $9.0 million in Q3 2024 [12] - Cash on hand remains strong at $1.3 billion, intended for investment in U S launches and pipeline development [10, 12, 15] - Net loss for Q3 2025 was $103.4 million, compared to a net income of $947.9 million in Q3 2024 [15] PYRUKYND® Commercial Progress - PYRUKYND net sales were $12.9 million in Q3 2025, compared to $12.5 million in Q2 2025 and $9.0 million in Q3 2024 [15, 20] - In the U S, 262 unique PK deficiency patients have completed prescription enrollment forms since launch [20] - There are 149 net patients on PYRUKYND treatment in the U S, including new prescriptions and treatment continuations [20] - PYRUKYND has been prescribed by 227 unique prescribers in the U S [20] Regulatory and Pipeline Advancements - PYRUKYND received SFDA approval in Saudi Arabia for thalassemia [12, 27, 28] - A positive CHMP opinion in Europe was received for PYRUKYND in thalassemia [12, 27, 28] - Enrollment is complete in the tebapivat Phase 2b trial for lower-risk MDS, with top-line data anticipated in early 2026 [12, 27]

Core Viewpoint - Agios Pharmaceuticals, a partner of Avanzanite, has announced a regulatory update that may impact its operations and market position [1] Group 1: Company Updates - Agios Pharmaceuticals is actively engaging with regulatory bodies to ensure compliance and advance its product pipeline [1] - The regulatory update is expected to provide clarity on the approval process for Agios's key therapies, which could influence future revenue streams [1] Group 2: Industry Implications - The biopharma industry is closely monitoring regulatory changes as they can significantly affect drug development timelines and market entry [1] - Successful navigation of regulatory hurdles is critical for biopharma companies to maintain competitive advantage and investor confidence [1]

Core Viewpoint - Agios Pharmaceuticals has received a positive opinion from the CHMP of the EMA for the new indication of PYRUKYND® (mitapivat) to treat anemia associated with both transfusion-dependent and non-transfusion-dependent alpha- or beta-thalassemia in adults [1][2][3] Company Developments - The CHMP's opinion is based on results from the global, randomized, double-blind, placebo-controlled ENERGIZE-T and ENERGIZE Phase 3 trials [2] - Agios has entered into an exclusive agreement with Avanzanite Bioscience B.V. for the commercialization and distribution of PYRUKYND across the European Economic Area, the UK, and Switzerland [3] - PYRUKYND has already received approval in Saudi Arabia for treating adult patients with both types of thalassemia [4] Clinical Trials - The ENERGIZE trial involved 194 non-transfusion-dependent patients, with a primary endpoint of achieving a hemoglobin response defined as an increase of ≥1.0 g/dL [10] - The ENERGIZE-T trial included 258 transfusion-dependent patients, focusing on a transfusion reduction response defined as a ≥50% reduction in transfused RBC units [11] Disease Background - Thalassemia is a rare inherited blood disease affecting hemoglobin production, categorized into alpha-thalassemia and beta-thalassemia [6] - An estimated 18,000 to 23,000 individuals are living with thalassemia in the U.S. and the five largest European countries [8]

Core Viewpoint - The Schall Law Firm is investigating Agios Pharmaceuticals, Inc. for potential violations of securities laws related to misleading statements and undisclosed information affecting investors [2]. Group 1: Investigation Details - The investigation centers on whether Agios issued false or misleading statements or failed to disclose critical information to investors [2]. - On September 4, 2025, Agios announced that the FDA extended the PDUFA goal date for the supplemental New Drug Application of PYRUKYND® by three months to December 7, 2025 [2]. - Following this announcement, Agios shares dropped by over 11% the next day [2]. Group 2: Legal Representation - The Schall Law Firm is representing investors globally and specializes in securities class action lawsuits and shareholder rights litigation [3]. - Shareholders who suffered losses are encouraged to contact the firm for a free discussion of their rights [3].

Core Viewpoint - Pomerantz LLP is investigating potential securities fraud or unlawful business practices by Agios Pharmaceuticals and its officers or directors, following a significant stock price drop due to a delayed FDA review of a key drug [1][3]. Group 1: Company Overview - Agios Pharmaceuticals, Inc. is under investigation for possible securities fraud related to its business practices [1]. - The company’s stock price fell by $4.48, or 11.03%, closing at $36.13 per share on September 4, 2025, after the announcement of a three-month extension for the FDA review of its drug PYRUKYND® [3]. Group 2: Regulatory Developments - The U.S. FDA extended the Prescription Drug User Fee Act (PDUFA) goal date for the supplemental New Drug Application (sNDA) of PYRUKYND® to December 7, 2025, impacting investor sentiment and stock performance [3].

Financial Performance - PYRUKYND net revenues reached $12.5 million in Q2 2025, a 44% increase compared to $8.7 million in Q1 2025 and a 45% increase compared to $8.6 million in Q2 2024[10] - The company maintains a strong financial position with $1.3 billion in cash on hand[9, 10, 14] - Net loss for Q2 2025 was $112.0 million, compared to a net loss of $96.1 million for Q2 2024[14] Pipeline Development - First patient dosed in Phase 2 Sickle Cell Disease trial for AG-236 after receiving IND clearance[11] - RISE UP Phase 3 trial in sickle cell disease is expected to have topline data by the end of 2025[37] - Tebapivat Phase 2b trial for LR-MDS is ongoing, with topline results expected in early 2026[9, 45] Commercialization - 248 unique PK deficiency patients completed prescription enrollment forms since launch in the U S [21] - 142 patients are on treatment in the U S , including new prescriptions and treatment continuations, with 215 unique prescribers[22] - The company anticipates a potential U S launch of PYRUKYND for thalassemia in Q3 2025, with a PDUFA goal date of September 7, 2025[11, 23, 24] Strategic Partnerships - Announced a commercialization and distribution partnership with Avanzanite Bioscience in Europe[10] - A commercialization and distribution agreement is in place with NewBridge for the GCC region, with anticipated first regulatory approval in the coming months[30]

Business Overview - Agios views PYRUKYND® as having a multi-billion dollar market opportunity [9] - Agios aims to maximize the potential of the PYRUKYND® franchise and progress key pipeline programs in 2025 [11] - Agios anticipates several clinical and regulatory catalysts in 2025, including a potential FDA approval for PYRUKYND® in thalassemia with a PDUFA goal date of September 7, 2025 [13] Clinical Development - Approximately 67% of thalassemia patients are non-transfusion dependent, representing about 4,000 adults in the U S [19] - Approximately 33% of thalassemia patients are transfusion dependent, representing about 2,000 adults in the U S [19] - Agios's PYRUKYND® has the potential to be the first and only approved therapy for all subtypes of thalassemia [23] - The Phase 3 RISE UP study of PYRUKYND® in sickle cell disease completed enrollment in October 2024, with topline data expected in late 2025 [31] - Tebapivat's Phase 2b study in lower-risk MDS expects patient enrollment completion in late 2025 [34, 41] Commercial Performance & Financials - PYRUKYND® net revenue was $8 7 million for Q1 2025, compared to $8 2 million in Q1 2024 [68] - Agios had $1 4 billion in cash, cash equivalents, and marketable securities as of March 31, 2025 [68, 74]