Agios Pharmaceuticals presents updated PYRUKYND long-term extension data

Agios Pharmaceuticals reported new data from the ongoing extension study assessing the long-term efficacy and safety of PYRUKYND in adults with pyruvate kinase deficiency who had participated in one of the pivotal studies, ACTIVATE and ACTIVATE-T, conducted in not regularly transfused and regularly transfused adults with PK deficiency, respectively. PYRUKYND is a first-in-class, oral PK activator and the first approved disease-modifying therapy for patients in the U.S. and EU with this rare, debilitating, lifelong hemolytic anemia. Long-term extension data show that previously reported effects of PYRUKYND on hemoglobin and transfusion burden were maintained over time. As of the March 27, 2022 data cut-off, the median duration of hemoglobin response among the 31 hemoglobin responders from ACTIVATE and the long-term extension study was 18.3 months, with responses ongoing up to 32.9 months. Hemoglobin response rate among patients who switched from placebo in ACTIVATE to PYRUKYND in the extension study was similar to that observed in patients treated with PYRUKYND in ACTIVATE. All regularly transfused patients who achieved transfusion-free status in ACTIVATE-T with PYRUKYND treatment maintained transfusion-free status through the extension study for up to 38.3 months. PYRUKYND(R) was well tolerated, and the safety profile was consistent with that in ACTIVATE and ACTIVATE-T, as well as previous studies. Agios also presented data at ASH further supporting the potential of PYRUKYND to address hallmark symptoms and complications of PK deficiency. In an oral presentation, data from ACTIVATE, ACTIVATE-T and the long-term extension study were reported, showing that treatment with PYRUKYND was associated with long-term, durable and clinically meaningful improvements in signs, symptoms and functional impacts, irrespective of transfusion status. Patient-reported outcome improvements among patients treated with PYRUKYND were sustained over time in the long-term extension study through Week 84. At Week 84 of the LTE study, clinically meaningful improvements in PROs mean scores were achieved in more than half of patients. These results suggest that by improving health-related quality of life, treatment with PYRUKYND may provide meaningful patient-centric benefits. In a poster presentation, data from ACTIVATE and the long-term extension study were reported that showed meaningful long-term improvements in key systemic regulators of iron homeostasis and measures of iron overload – including erythroferrone, soluble transferrin receptor and hepcidin – continued up to 96 weeks in patients treated with PYRUKYND. Additionally, patients treated with PYRUKYND who had evidence of iron overload at baseline showed clinically meaningful and continued improvements in iron overload over time as measured by liver iron concentration. Ferritin levels remained stable across both patient groups treated with PYRUKYND or placebo. In a separate poster presentation, data from the ACTIVATE study were reported showing that treatment with PYRUKYND improved markers of hemolysis and ineffective erythropoiesis in adults with PK deficiency. The analysis also shows that directional improvements occur even in patients who did not achieve the clinical trial definition of hemoglobin response. PYRUKYND was approved in February 2022 by the U.S. Food and Drug Administration and received marketing authorization in November 2022 by the European Medicines Agency for adults with PK deficiency. Both the FDA and EMA have granted orphan drug designation to PYRUKYND in PK deficiency. In addition, PYRUKYND has been granted FDA orphan drug designation for the treatment of thalassemia and sickle cell disease, for which enrollment for ongoing pivotal studies is underway.