Clinical results demonstrated durable improvement in hematologic and hemolytic markers, supporting the potential for improvement of red blood cell functional health in those with sickle cell disease
Initial results from an open-label extension cohort showed sustained hemoglobin increase of >1g/dL in 88% (7 of 8) of patients dosed for at least two and up to 12 weeks, as well as favorable tolerability profile
Improvement in markers of red blood cell functional health were observed, including data on measures of cell membrane integrity and systemic biomarkers of inflammation and coagulation
WATERTOWN, MA, USA I June 11, 2021 IForma Therapeutics Holdings, Inc. (Nasdaq: FMTX) a clinical-stage biopharmaceutical company focused on rare hematologic diseases and cancers, today announced new data from its ongoing Phase 1 trial of etavopivat (formerly referred to as FT-4202) being presented at the 26th Annual European Hematology Association (EHA) 2021 Virtual Congress. The e-poster presentation includes initial data from the open-label extension (OLE) cohort showing etavopivat improved and sustained hematologic and hemolytic parameters for patients living with sickle cell disease (SCD) receiving 400 mg etavopivat once-daily for at least two weeks and up to 12 weeks. Also being presented are the unblinded results from the two multiple ascending dose (MAD) cohorts, which demonstrate once-daily dosing of 300 mg or 600 mg etavopivat for 14 days improved measures of sickle red blood cell (RBC) functional health, with effects persisting in some patients even after treatment discontinuation.
“Data presented today, including initial data from the OLE cohort, demonstrate patient responses improved with more than two weeks of dosing with etavopivat, including hemoglobin and markers of hemolysis, RBC functional health, and systemic inflammation and coagulation that together have the potential to reduce the incidence of vaso-occlusive crises with longer-term treatment,” said Patrick Kelly, M.D., chief medical officer of Forma Therapeutics. “These results, along with the favorable tolerability profile we have observed, support our recent initiation of the Hibiscus Study – our Phase 2/3 trial in people living with SCD – and bring us one step closer to a potential new treatment option for those affected by SCD.”
Presentation Details
- Abstract #EP1201: FT-4202 (Etavopivat) improves hematologic and hemolytic parameters in a phase 1 study of patients with sickle cell disease (Robert Clark Brown, M.D., Ph.D)
The e-poster presentation is available as of Friday, June 11, 2021, at 9:00 Central European Summer Time (CEST) and is accessible for on-demand viewing until Sunday, August 15, 2021, on EHA’s virtual congress platform. The abstract and poster presentation are also available on Forma’s website.
Clinical Data Results
In the combined MAD1 (300 mg QD) and MAD2 (600 mg QD) cohorts, 73% (11 of 15) of patients achieved a hemoglobin increase of greater than 1g/dL over baseline; significant improvement in hematologic and hemolytic markers also included decreased absolute reticulocytes (100%, or 15 of 15), decreased LDH levels (73%, or 11 of 15) and decreased indirect bilirubin levels (93%, or 14 of 15). The osmoscan and oxygenscan results from 14 patients showed a statistically significant improvement.
Initial results as of May 24, 2021 in the OLE cohort for eight patients receiving etavopivat treatment (400 mg QD) for at least two weeks indicated a hemoglobin increase of greater than 1 g/dL in 88% (7 of 8), with a mean hemoglobin increase of 1.5 g/dL. Patient data indicated a durable response for those patients receiving treatment beyond two weeks, for up to 12 weeks, with improved hematologic and hemolytic parameters. The improvement in RBC functional health extended beyond the 12-week treatment period; in one patient, improved sickle RBC deformability remained for up to four weeks after treatment discontinuation. These initial OLE data support the combined MAD cohort results and show that daily etavopivat treatment also significantly improved hematologic and hemolytic parameters.
The safety profile in the OLE cohort was consistent with underlying disease. Of note, two patients reported serious adverse events, including one vaso-occlusive crisis and acute chest syndrome, which was not considered related to treatment by the trial investigator. A deep-vein thrombosis (DVT) report was described as possibly related.
Additional results being presented at the conference are measures of RBC functional health, with RBC elongation and point-of-sickling data analysis showing improvements in cell deformability, including durable changes for up to four weeks following treatment. The data show benefits beyond activation of the glycolytic pathway, including enhanced activity of enzymes involved in preventing and repairing oxidative damage and reduced levels of phosphatidyl serine (PS), a marker of membrane damage observed on the surface of sickle RBCs. Early data from the 12-week OLE cohort show favorable systemic biomarkers including lower levels of erythropoietin (EPO), reduced evidence of activation of coagulation (Prothrombin 1.2 and D-dimers) and decreased activation of innate immunity (TNF-a). These biomarkers suggest the potential for a broader benefit to people living with SCD, including the potential to reduce vaso-occlusive crises.
Forma Webcast Today
Forma is hosting a webcast today at 8:00 a.m. ET to discuss these etavopivat results being presented at EHA. The webcast can be accessed in the “News & Investors” section of Forma’s website at www.formatherapeutics.com.
Ongoing Trials
The blinded, randomized, placebo-controlled portion of the ongoing Phase 1 trial is complete. People with SCD are now directly enrolling into the ongoing 12-week OLE cohort receiving 400 mg etavopivat daily.
Forma is currently enrolling adults and adolescents with SCD into the Hibiscus Study, a registrational Phase 2/3 randomized, placebo-controlled, double-blind, multicenter trial to further evaluate the safety and efficacy of etavopivat in this patient population. For more information, please visit https://hibiscusstudy.com/ or clinicaltrials.gov/NCT04624659.
About Sickle Cell Disease (SCD)
SCD is one of the most common single-gene disorders and is estimated to affect approximately 100,000 people in the United States, as well as approximately 30,000 in France, Germany, Italy, Spain and the United Kingdom. The National Institutes of Health (NIH) reports that prevalence is estimated at more than 20 million individuals globally. From 2010 to 2050, the annual number of newborns with SCD is expected to rise globally by approximately one-third.i Despite recent advances in treatment, most patients with SCD still suffer from pain crises, lifelong disability, significant morbidity and reduced quality of life.
About Etavopivat
Etavopivat is a novel investigational selective red blood cell (RBC) pyruvate kinase-R (PKR) activator designed to be a disease-modifying therapy for the treatment of sickle cell disease (SCD). Employing a multimodal approach, etavopivat is designed to work upstream by activating the RBCs’ natural PKR activity to decrease 2,3-DPG levels, which leads hemoglobin to hold on to oxygen molecules longer to reduce RBC sickling. The downstream activity of etavopivat is designed to increase ATP levels, the fuel that provides energy to cells, to improve RBC functional health and survival. Together, these effects are anticipated to increase hemoglobin levels and decrease painful vaso-occlusive crises. In preclinical safety studies, etavopivat did not inhibit aromatase activity or affect steroidogenesis, important biological processes responsible for sexual development. Etavopivat has been granted Fast Track, Rare Pediatric Disease and Orphan Drug designations from the U.S. Food and Drug Administration (FDA), and Orphan Drug Designation from the European Commission based on a positive opinion from the Committee for Orphan Medicinal Products of the European Medicines Agency for the treatment of patients with SCD.
About Forma Therapeutics
Forma Therapeutics is a clinical-stage biopharmaceutical company focused on the research, development and commercialization of novel therapeutics to transform the lives of patients with rare hematologic diseases and cancers. Our R&D engine combines deep biology insight, chemistry expertise and clinical development capabilities to create drug candidates with differentiated mechanisms of action focused on indications with high unmet need. Our work has generated a broad proprietary portfolio of programs with the potential to provide profound patient benefit. For more information, please visit www.FormaTherapeutics.com or follow us on Twitter @FORMAInc and LinkedIn.
i Piel, F. B., Hay, S. I., Gupta, S., Weatherall, D. J., & Williams, T. N. (2013). Global burden of sickle cell anaemia in children under five, 2010-2015: Modelling based on demographics, excess mortality, and interventions. PLOS Medicine, 10(7). Retrieved from link.
SOURCE: Forma Therapeutics
Post Views: 349
Clinical results demonstrated durable improvement in hematologic and hemolytic markers, supporting the potential for improvement of red blood cell functional health in those with sickle cell disease
Initial results from an open-label extension cohort showed sustained hemoglobin increase of >1g/dL in 88% (7 of 8) of patients dosed for at least two and up to 12 weeks, as well as favorable tolerability profile
Improvement in markers of red blood cell functional health were observed, including data on measures of cell membrane integrity and systemic biomarkers of inflammation and coagulation
WATERTOWN, MA, USA I June 11, 2021 IForma Therapeutics Holdings, Inc. (Nasdaq: FMTX) a clinical-stage biopharmaceutical company focused on rare hematologic diseases and cancers, today announced new data from its ongoing Phase 1 trial of etavopivat (formerly referred to as FT-4202) being presented at the 26th Annual European Hematology Association (EHA) 2021 Virtual Congress. The e-poster presentation includes initial data from the open-label extension (OLE) cohort showing etavopivat improved and sustained hematologic and hemolytic parameters for patients living with sickle cell disease (SCD) receiving 400 mg etavopivat once-daily for at least two weeks and up to 12 weeks. Also being presented are the unblinded results from the two multiple ascending dose (MAD) cohorts, which demonstrate once-daily dosing of 300 mg or 600 mg etavopivat for 14 days improved measures of sickle red blood cell (RBC) functional health, with effects persisting in some patients even after treatment discontinuation.
“Data presented today, including initial data from the OLE cohort, demonstrate patient responses improved with more than two weeks of dosing with etavopivat, including hemoglobin and markers of hemolysis, RBC functional health, and systemic inflammation and coagulation that together have the potential to reduce the incidence of vaso-occlusive crises with longer-term treatment,” said Patrick Kelly, M.D., chief medical officer of Forma Therapeutics. “These results, along with the favorable tolerability profile we have observed, support our recent initiation of the Hibiscus Study – our Phase 2/3 trial in people living with SCD – and bring us one step closer to a potential new treatment option for those affected by SCD.”
Presentation Details
- Abstract #EP1201: FT-4202 (Etavopivat) improves hematologic and hemolytic parameters in a phase 1 study of patients with sickle cell disease (Robert Clark Brown, M.D., Ph.D)
The e-poster presentation is available as of Friday, June 11, 2021, at 9:00 Central European Summer Time (CEST) and is accessible for on-demand viewing until Sunday, August 15, 2021, on EHA’s virtual congress platform. The abstract and poster presentation are also available on Forma’s website.
Clinical Data Results
In the combined MAD1 (300 mg QD) and MAD2 (600 mg QD) cohorts, 73% (11 of 15) of patients achieved a hemoglobin increase of greater than 1g/dL over baseline; significant improvement in hematologic and hemolytic markers also included decreased absolute reticulocytes (100%, or 15 of 15), decreased LDH levels (73%, or 11 of 15) and decreased indirect bilirubin levels (93%, or 14 of 15). The osmoscan and oxygenscan results from 14 patients showed a statistically significant improvement.
Initial results as of May 24, 2021 in the OLE cohort for eight patients receiving etavopivat treatment (400 mg QD) for at least two weeks indicated a hemoglobin increase of greater than 1 g/dL in 88% (7 of 8), with a mean hemoglobin increase of 1.5 g/dL. Patient data indicated a durable response for those patients receiving treatment beyond two weeks, for up to 12 weeks, with improved hematologic and hemolytic parameters. The improvement in RBC functional health extended beyond the 12-week treatment period; in one patient, improved sickle RBC deformability remained for up to four weeks after treatment discontinuation. These initial OLE data support the combined MAD cohort results and show that daily etavopivat treatment also significantly improved hematologic and hemolytic parameters.
The safety profile in the OLE cohort was consistent with underlying disease. Of note, two patients reported serious adverse events, including one vaso-occlusive crisis and acute chest syndrome, which was not considered related to treatment by the trial investigator. A deep-vein thrombosis (DVT) report was described as possibly related.
Additional results being presented at the conference are measures of RBC functional health, with RBC elongation and point-of-sickling data analysis showing improvements in cell deformability, including durable changes for up to four weeks following treatment. The data show benefits beyond activation of the glycolytic pathway, including enhanced activity of enzymes involved in preventing and repairing oxidative damage and reduced levels of phosphatidyl serine (PS), a marker of membrane damage observed on the surface of sickle RBCs. Early data from the 12-week OLE cohort show favorable systemic biomarkers including lower levels of erythropoietin (EPO), reduced evidence of activation of coagulation (Prothrombin 1.2 and D-dimers) and decreased activation of innate immunity (TNF-a). These biomarkers suggest the potential for a broader benefit to people living with SCD, including the potential to reduce vaso-occlusive crises.
Forma Webcast Today
Forma is hosting a webcast today at 8:00 a.m. ET to discuss these etavopivat results being presented at EHA. The webcast can be accessed in the “News & Investors” section of Forma’s website at www.formatherapeutics.com.
Ongoing Trials
The blinded, randomized, placebo-controlled portion of the ongoing Phase 1 trial is complete. People with SCD are now directly enrolling into the ongoing 12-week OLE cohort receiving 400 mg etavopivat daily.
Forma is currently enrolling adults and adolescents with SCD into the Hibiscus Study, a registrational Phase 2/3 randomized, placebo-controlled, double-blind, multicenter trial to further evaluate the safety and efficacy of etavopivat in this patient population. For more information, please visit https://hibiscusstudy.com/ or clinicaltrials.gov/NCT04624659.
About Sickle Cell Disease (SCD)
SCD is one of the most common single-gene disorders and is estimated to affect approximately 100,000 people in the United States, as well as approximately 30,000 in France, Germany, Italy, Spain and the United Kingdom. The National Institutes of Health (NIH) reports that prevalence is estimated at more than 20 million individuals globally. From 2010 to 2050, the annual number of newborns with SCD is expected to rise globally by approximately one-third.i Despite recent advances in treatment, most patients with SCD still suffer from pain crises, lifelong disability, significant morbidity and reduced quality of life.
About Etavopivat
Etavopivat is a novel investigational selective red blood cell (RBC) pyruvate kinase-R (PKR) activator designed to be a disease-modifying therapy for the treatment of sickle cell disease (SCD). Employing a multimodal approach, etavopivat is designed to work upstream by activating the RBCs’ natural PKR activity to decrease 2,3-DPG levels, which leads hemoglobin to hold on to oxygen molecules longer to reduce RBC sickling. The downstream activity of etavopivat is designed to increase ATP levels, the fuel that provides energy to cells, to improve RBC functional health and survival. Together, these effects are anticipated to increase hemoglobin levels and decrease painful vaso-occlusive crises. In preclinical safety studies, etavopivat did not inhibit aromatase activity or affect steroidogenesis, important biological processes responsible for sexual development. Etavopivat has been granted Fast Track, Rare Pediatric Disease and Orphan Drug designations from the U.S. Food and Drug Administration (FDA), and Orphan Drug Designation from the European Commission based on a positive opinion from the Committee for Orphan Medicinal Products of the European Medicines Agency for the treatment of patients with SCD.
About Forma Therapeutics
Forma Therapeutics is a clinical-stage biopharmaceutical company focused on the research, development and commercialization of novel therapeutics to transform the lives of patients with rare hematologic diseases and cancers. Our R&D engine combines deep biology insight, chemistry expertise and clinical development capabilities to create drug candidates with differentiated mechanisms of action focused on indications with high unmet need. Our work has generated a broad proprietary portfolio of programs with the potential to provide profound patient benefit. For more information, please visit www.FormaTherapeutics.com or follow us on Twitter @FORMAInc and LinkedIn.
i Piel, F. B., Hay, S. I., Gupta, S., Weatherall, D. J., & Williams, T. N. (2013). Global burden of sickle cell anaemia in children under five, 2010-2015: Modelling based on demographics, excess mortality, and interventions. PLOS Medicine, 10(7). Retrieved from link.
SOURCE: Forma Therapeutics
Post Views: 349
