CAMBRIDGE, MA, USA I June 7, 2016 I Catabasis Pharmaceuticals, Inc. (NASDAQ:CATB), a clinical-stage biopharmaceutical company, today announced top-line results from its Phase 2a clinical trial of CAT-2054 for the treatment of hypercholesterolemia. CAT-2054 is an oral product candidate that inhibits Sterol Regulatory Element-Binding Protein (SREBP), a master regulator of lipid metabolism in the body. The double-blind, placebo-controlled trial assessed the effects of four weeks of treatment with CAT-2054 in patients with hypercholesterolemia on a high-intensity statin. The trial did not meet the primary end point in hypercholesterolemia, reduction in LDL-cholesterol (LDL-C) from baseline. Additional pre-specified analyses included changes in liver function tests (LFTs) to assess potential activity in nonalcoholic steatohepatitis (NASH). In a pre-specified analysis of patients more likely to have NASH, a potentially favorable pattern in LFTs was seen despite relatively low baseline LFT values and short trial duration and needs further investigation. All four doses of CAT-2054 in the trial were generally well tolerated.
In this Phase 2a trial, 153 patients were randomized with 94.8% completing the trial. The most common adverse events (AEs) were nausea, diarrhea and urinary tract infection (9%, 8% and 5% for CAT-2054 versus 3%, 0% and 10% for placebo, respectively), and four patients discontinued because of AEs. There were no treatment-related serious AEs. Catabasis plans to submit the data from this trial for presentation at an upcoming medical meeting.
“While CAT-2054 lowered LDL-C in normal healthy volunteers in its Phase 1 clinical trial, this effect was not observed in this Phase 2a trial in patients with hypercholesterolemia who were also on high-intensity statins,” said Jill C. Milne, Ph.D., Chief Executive Officer of Catabasis. “The trial was well designed and efficiently run, enabling us to quickly determine that we do not expect to invest further in CAT-2054 for hypercholesterolemia. We plan to complete additional analysis of the data and determine the best path forward for CAT-2054 in NASH. Our corporate strategy remains focused on our lead program, edasalonexent (CAT-1004) in Duchenne muscular dystrophy.”
“There is substantial mechanistic support for the role of SREBP in NASH and the recently presented preclinical data with a CAT-2054 analog are compelling. While this trial in a hypercholesterolemic population was not designed to assess NASH signals, the safety and LFTs observations support further exploration in NASH,” said Arun Sanyal, M.D., Professor of Medicine in the Gastroenterology Division of Virginia Commonwealth University Medical Center.
The CAT-2054 Phase 2a trial was a randomized, double-blind, placebo-controlled trial conducted at 31 clinical trial sites that enrolled 153 patients with hypercholesterolemia on statins. After a 4-week run-in on atorvastatin 40 mg, patients were randomized into one of four treatment groups (CAT-2054 250 mg or 400 mg once daily or twice daily) or placebo. The patients in this trial had hypercholesterolemia on statins with LDL cholesterol levels over 70 and less than 190 mg/dL. At baseline, mean LDL levels were 103 mg/dL, 30% of the patients had type 2 diabetes and 60% had metabolic syndrome. After four weeks of dosing with CAT-2054, the maximum LDL-C decrease observed was 7.1% compared to 4.5% with placebo. Additional secondary lipid end points included triglycerides and non-HDL cholesterol and these did not change significantly with treatment. In one pre-specified analysis, in a subset of the patients more likely to have NASH as determined by FIB-4 (Fibrosis-4, a non-invasive scoring system based on several laboratory tests that estimate the amount of scarring in the liver), a potentially favorable pattern in LFTs was seen. In this subset of patients (N=51), from a mean baseline ALT of 26 UL/mL there was a mean reduction in ALT of 3.0 IU/mL across all dosing arms of CAT-2054 compared to a reduction of 0.2 IU/mL with placebo and from a mean baseline AST of 25 IU/mL there was a mean reduction in AST of 2.8 IU/mL for those treated with CAT-2054 compared to an increase of 0.2 IU/mL with placebo.
About CAT-2054
CAT-2054 is an oral small molecule with a novel mechanism of action being developed as a potential treatment for nonalcoholic steatohepatitis (NASH). CAT-2054 inhibits Sterol Regulatory Element-Binding Protein (SREBP), a master regulator of lipid metabolism in the body, which has the potential to reduce liver fat. We have shown in pre-clinical models of NASH that a CAT-2054 analog significantly improves liver inflammation, fibrosis, steatosis and pre-neoplastic lesions. In a Phase 2a trial in patients with hypercholesterolemia, CAT-2054 had no effect on LDL-C levels when co-administered with high intensity statins. In a pre-specified analysis of patients more likely to have NASH, a potentially favorable pattern in liver function tests (LFTs) was seen despite relatively low baseline LFT values and short trial duration and needs further investigation.
About Catabasis
At Catabasis Pharmaceuticals, our mission is to bring hope and life-changing therapies to patients and their families. Our SMART (Safely Metabolized And Rationally Targeted) linker drug discovery platform enables us to engineer molecules that simultaneously modulate multiple targets in a disease. We are applying our SMART linker platform to build an internal pipeline of product candidates for rare diseases and plan to pursue partnerships to develop additional product candidates. For more information on the Company’s drug discovery platform and pipeline of drug candidates, please visit www.catabasis.com.
SOURCE: Catabasis Pharmaceuticals
Post Views: 162
CAMBRIDGE, MA, USA I June 7, 2016 I Catabasis Pharmaceuticals, Inc. (NASDAQ:CATB), a clinical-stage biopharmaceutical company, today announced top-line results from its Phase 2a clinical trial of CAT-2054 for the treatment of hypercholesterolemia. CAT-2054 is an oral product candidate that inhibits Sterol Regulatory Element-Binding Protein (SREBP), a master regulator of lipid metabolism in the body. The double-blind, placebo-controlled trial assessed the effects of four weeks of treatment with CAT-2054 in patients with hypercholesterolemia on a high-intensity statin. The trial did not meet the primary end point in hypercholesterolemia, reduction in LDL-cholesterol (LDL-C) from baseline. Additional pre-specified analyses included changes in liver function tests (LFTs) to assess potential activity in nonalcoholic steatohepatitis (NASH). In a pre-specified analysis of patients more likely to have NASH, a potentially favorable pattern in LFTs was seen despite relatively low baseline LFT values and short trial duration and needs further investigation. All four doses of CAT-2054 in the trial were generally well tolerated.
In this Phase 2a trial, 153 patients were randomized with 94.8% completing the trial. The most common adverse events (AEs) were nausea, diarrhea and urinary tract infection (9%, 8% and 5% for CAT-2054 versus 3%, 0% and 10% for placebo, respectively), and four patients discontinued because of AEs. There were no treatment-related serious AEs. Catabasis plans to submit the data from this trial for presentation at an upcoming medical meeting.
“While CAT-2054 lowered LDL-C in normal healthy volunteers in its Phase 1 clinical trial, this effect was not observed in this Phase 2a trial in patients with hypercholesterolemia who were also on high-intensity statins,” said Jill C. Milne, Ph.D., Chief Executive Officer of Catabasis. “The trial was well designed and efficiently run, enabling us to quickly determine that we do not expect to invest further in CAT-2054 for hypercholesterolemia. We plan to complete additional analysis of the data and determine the best path forward for CAT-2054 in NASH. Our corporate strategy remains focused on our lead program, edasalonexent (CAT-1004) in Duchenne muscular dystrophy.”
“There is substantial mechanistic support for the role of SREBP in NASH and the recently presented preclinical data with a CAT-2054 analog are compelling. While this trial in a hypercholesterolemic population was not designed to assess NASH signals, the safety and LFTs observations support further exploration in NASH,” said Arun Sanyal, M.D., Professor of Medicine in the Gastroenterology Division of Virginia Commonwealth University Medical Center.
The CAT-2054 Phase 2a trial was a randomized, double-blind, placebo-controlled trial conducted at 31 clinical trial sites that enrolled 153 patients with hypercholesterolemia on statins. After a 4-week run-in on atorvastatin 40 mg, patients were randomized into one of four treatment groups (CAT-2054 250 mg or 400 mg once daily or twice daily) or placebo. The patients in this trial had hypercholesterolemia on statins with LDL cholesterol levels over 70 and less than 190 mg/dL. At baseline, mean LDL levels were 103 mg/dL, 30% of the patients had type 2 diabetes and 60% had metabolic syndrome. After four weeks of dosing with CAT-2054, the maximum LDL-C decrease observed was 7.1% compared to 4.5% with placebo. Additional secondary lipid end points included triglycerides and non-HDL cholesterol and these did not change significantly with treatment. In one pre-specified analysis, in a subset of the patients more likely to have NASH as determined by FIB-4 (Fibrosis-4, a non-invasive scoring system based on several laboratory tests that estimate the amount of scarring in the liver), a potentially favorable pattern in LFTs was seen. In this subset of patients (N=51), from a mean baseline ALT of 26 UL/mL there was a mean reduction in ALT of 3.0 IU/mL across all dosing arms of CAT-2054 compared to a reduction of 0.2 IU/mL with placebo and from a mean baseline AST of 25 IU/mL there was a mean reduction in AST of 2.8 IU/mL for those treated with CAT-2054 compared to an increase of 0.2 IU/mL with placebo.
About CAT-2054
CAT-2054 is an oral small molecule with a novel mechanism of action being developed as a potential treatment for nonalcoholic steatohepatitis (NASH). CAT-2054 inhibits Sterol Regulatory Element-Binding Protein (SREBP), a master regulator of lipid metabolism in the body, which has the potential to reduce liver fat. We have shown in pre-clinical models of NASH that a CAT-2054 analog significantly improves liver inflammation, fibrosis, steatosis and pre-neoplastic lesions. In a Phase 2a trial in patients with hypercholesterolemia, CAT-2054 had no effect on LDL-C levels when co-administered with high intensity statins. In a pre-specified analysis of patients more likely to have NASH, a potentially favorable pattern in liver function tests (LFTs) was seen despite relatively low baseline LFT values and short trial duration and needs further investigation.
About Catabasis
At Catabasis Pharmaceuticals, our mission is to bring hope and life-changing therapies to patients and their families. Our SMART (Safely Metabolized And Rationally Targeted) linker drug discovery platform enables us to engineer molecules that simultaneously modulate multiple targets in a disease. We are applying our SMART linker platform to build an internal pipeline of product candidates for rare diseases and plan to pursue partnerships to develop additional product candidates. For more information on the Company’s drug discovery platform and pipeline of drug candidates, please visit www.catabasis.com.
SOURCE: Catabasis Pharmaceuticals
Post Views: 162
