{"id":793234,"date":"2024-12-08T12:43:07","date_gmt":"2024-12-08T17:43:07","guid":{"rendered":"https:\/\/www.marketnewsdesk.com\/index.php\/agios-presents-positive-results-from-phase-3-energize-t-study-of-mitapivat-at-ash-2024-and-provides-regulatory-update-on-mitapivat\/"},"modified":"2024-12-08T12:43:07","modified_gmt":"2024-12-08T17:43:07","slug":"agios-presents-positive-results-from-phase-3-energize-t-study-of-mitapivat-at-ash-2024-and-provides-regulatory-update-on-mitapivat","status":"publish","type":"post","link":"https:\/\/www.marketnewsdesk.com\/index.php\/agios-presents-positive-results-from-phase-3-energize-t-study-of-mitapivat-at-ash-2024-and-provides-regulatory-update-on-mitapivat\/","title":{"rendered":"Agios Presents Positive Results from Phase 3 ENERGIZE-T Study of Mitapivat\u00a0at ASH 2024 and Provides Regulatory Update on Mitapivat"},"content":{"rendered":"
\n

\n \u2013 ENERGIZE-T Study Achieved Primary and All Key Secondary Endpoints in Adult Patients with Transfusion-Dependent Alpha- or Beta-Thalassemia \u2013<\/em>\n <\/p>\n

\n \u2013 ENERGIZE-T is First Phase 3 Study to Demonstrate Efficacy of an Oral, Disease-Modifying Treatment for Transfusion-Dependent Alpha- and Beta-Thalassemia\u00a0\u2013<\/em>\n <\/p>\n

\n \u2013 Company Filed for Regulatory Approval of Mitapivat (PYRUKYND<\/em>
\n
\n \u00ae<\/em>
\n <\/sup>
\n ) for the Treatment of Adult Patients with Non-Transfusion-Dependent and Transfusion-Dependent Alpha- or Beta-Thalassemia in U.S., European Union, Kingdom of Saudi Arabia and United Arab Emirates \u2013<\/em>
\n \n <\/p>\n

\n \u2013 Live and Webcast Investor Event with Agios Leadership and Medical Experts will be Hosted in San Diego on\u00a0Monday, December 9\u00a0at 7:00 a.m. PT \u2013<\/em>\n <\/p>\n

CAMBRIDGE, Mass., Dec. 08, 2024 (GLOBE NEWSWIRE) — Agios Pharmaceuticals, Inc. (Nasdaq: AGIO), a leader in cellular metabolism and pyruvate kinase (PK) activation pioneering therapies for rare diseases, today presented positive results from the Phase 3 ENERGIZE-T study investigating mitapivat, an oral, small molecule PK activator, in adults with transfusion-dependent alpha- or beta-thalassemia. These findings were shared in an oral presentation (abstract #409) at the 66th<\/sup> American Society of Hematology (ASH) Annual Meeting and Exposition in San Diego, California.<\/p>\n

Thalassemia is a rare inherited blood disorder caused by genetic mutations that lead to a reduced production of healthy hemoglobin, compromising red blood cell development, health and survival, and resulting in chronic anemia. Patients with thalassemia often experience a range of debilitating complications, both from the disease itself and as secondary effects of common management strategies such as blood transfusions and iron chelation therapy, including organ damage, stroke, and other serious health issues.<\/p>\n

In the ENERGIZE-T trial, mitapivat demonstrated a statistically significant reduction in transfusion burden compared to placebo in patients with transfusion-dependent alpha- or beta-thalassemia, achieving its primary endpoint. Additionally, the ENERGIZE-T study met all the key secondary endpoints, with mitapivat demonstrating a statistically significant reduction in additional measures of transfusion reduction response compared to placebo. In June 2024, Agios also presented positive results<\/a> from the Phase 3 ENERGIZE study, which evaluated mitapivat in adults with non-transfusion-dependent alpha- or beta-thalassemia.<\/p>\n

\u201cTreatment options for patients with transfusion-dependent thalassemia are extremely limited, and transfusions carry serious risks, such as iron overload, infections and immune reactions. There is a significant need for alternative treatments to manage this debilitating disease,\u201d said\u00a0Maria Domenica Cappellini, M.D., professor, Internal Medicine,\u00a0University of Milan, Italy. \u201cThe strong Phase 3 ENERGIZE-T results build on the positive findings from the Phase 3 ENERGIZE study in patients with non-transfusion-dependent alpha- or beta-thalassemia presented earlier this year, pointing to mitapivat as a potential transformative advancement in thalassemia care.\u201d<\/p>\n

\n Phase 3 ENERGIZE-T Study Results<\/strong>
\n
ENERGIZE-T is a Phase 3, double-blind, randomized, placebo-controlled and multicenter 48-week study. A total of 258 patients were enrolled in the study worldwide, with 171 patients randomized to mitapivat 100 mg twice-daily (BID) and 87 patients randomized to matched placebo.<\/p>\n

The study\u2019s primary endpoint of transfusion reduction response (TRR) was defined as a \u226550% reduction in transfused red blood cell (RBC) units with a reduction of \u22652 units of transfused RBCs in any consecutive 12-week period through Week 48 compared with baseline. A TRR was achieved by 30.4% (n=52\/171) of patients in the mitapivat arm compared to 12.6% (n=11\/87) of patients in the placebo arm (2-sided p=0.0003).<\/p>\n

Additionally, mitapivat demonstrated statistically significant reductions in transfusion burden compared with placebo as measured by the three key secondary endpoints of transfusion reduction response reflective of durability of response up to 36 weeks during the 48-week double-blind period. The key secondary endpoint TRR2, defined as a \u226550% reduction in transfused RBC units in any consecutive 24-week period through Week 48 compared with baseline, was achieved in 13.5% (n=23\/171) versus 2.3% (n=2\/87) of patients in the mitapivat and placebo arms, respectively (2-sided p=0.0003).\u00a0The key secondary endpoints TRR3 and TRR4 were defined as a \u226533% and \u226550% reduction in transfused RBC units, respectively, from Week 13 through Week 48 compared with baseline.\u00a0TRR3 was achieved in 14.6% (n=25\/171) versus 1.1% (n=1\/87) of patients in the mitapivat and placebo arms, respectively (2-sided p<0.0001), and TRR4 was achieved in 7.6% (n=13\/171) versus 1.1% (n=1\/87) of patients in the mitapivat and placebo arms, respectively (2-sided p=0.0056).\u00a0<\/p>\n

The results for the primary and key secondary endpoints were not driven by any of the individual prespecified subgroups, including but not limited to genotype and baseline transfusion burden, highlighting the overall robustness of the efficacy results.<\/p>\n

Further, 17 patients (9.9%) in the mitapivat arm compared with one patient (1.1%) in the placebo arm achieved the secondary endpoint of transfusion independence (transfusion-free for 8 or more consecutive weeks through Week 48). Three patients in the mitapivat arm did not receive any transfusions during the 48-week double-blind period.<\/p>\n

Overall, during the 48-week double-blind period, incidence of adverse events (AEs) was similar across the mitapivat and placebo arms. The proportion of patients with any treatment-emergent adverse events (TEAEs) was 90.1% (n=155) in patients on mitapivat and 83.5% (n=71) in patients on placebo. The most frequent TEAEs that occurred in at least 10% of patients on mitapivat were headache, upper respiratory tract infection, initial insomnia, diarrhea and fatigue.\u00a0Serious treatment-emergent adverse events were reported in 11.0% (n=19) and 15.3% (n=13) of patients on mitapivat and placebo, respectively; 2.3% (n=4) and 1.2% (n=1), respectively, were considered treatment-related.\u00a0There were 5.8% (n=10) of patients on mitapivat and 1.2% (n=1) on placebo with TEAEs leading to treatment discontinuation.\u00a0The TEAEs leading to discontinuation of mitapivat, each of which occurred in one patient, were diarrhea, paresthesia oral, concurrent anxiety and insomnia, initial insomnia, supraventricular tachycardia, fatigue, hypertransaminasemia, hepatitis C, hepatic cancer, and renal mass. The TEAE that led to discontinuation of the one patient on placebo was blood creatine phosphokinase increased.<\/p>\n

\n Mitapivat Thalassemia Regulatory Next Steps <\/strong>
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Currently, there are no disease-modifying therapies approved to treat the full spectrum of patients with thalassemia across transfusion requirements and genotypes. The standard of care for thalassemia remains centered on supportive care to address symptoms through transfusions, splenectomy, and\/or iron chelation therapy, none of which address the underlying pathophysiology of the disease.<\/p>\n

Based on the favorable benefit-risk profile observed in both the Phase 3 ENERGIZE and ENERGIZE-T studies, Agios filed regulatory applications for mitapivat (PYRUKYND\u00ae<\/sup>) for the treatment of adult patients with non-transfusion-dependent and transfusion-dependent alpha- or beta-thalassemia with the U.S., European Union, Kingdom of Saudi Arabia and United Arab Emirates health authorities.<\/p>\n

The Phase 3 ENERGIZE and ENERGIZE-T trials enrolled a total of 452 patients reflective of the real-world thalassemia population. The results demonstrated that mitapivat improves hemolytic anemia and quality-of-life related measures, as measured by significant reductions in transfusion burden and significant improvements in hemoglobin and fatigue.<\/p>\n