Date: 2015-08-13
Type of information: Results
phase: 1
Announcement: results
Company: Catabasis Pharmaceuticals (USA - MA)
Product: CAT-2054
Action
mechanism: SREBP (Sterol-regulatory element binding proteins) modulator. SREBP (Sterol-regulatory element binding proteins) is a master regulator of lipid and energy metabolism and controls the metabolism of both LDL-C and triglycerides. Important for cholesterol levels, SREBP controls expression of PCSK9, a protein that controls the clearance of LDL-C from circulation through the reduction of the amount of the LDL receptor on the surface of the liver; HMG-CoA reductase, an enzyme that plays a central role in the synthesis of LDL-C in the liver; and ATP citrate lyase, an enzyme in the LDL-C synthetic pathway; and Niemann-Pick C1-like 1 (NPC1L1), which is the critical mediator of cholesterol absorption in the gastrointestinal tract epithelial cells as well as in liver cells. These four proteins impact cholesterol clearance, synthesis and absorption. Important for triglyceride levels, SREBP also controls expression of three proteins: apolipoprotein C3 (ApoC3), angiopoietin-like protein 3 (Angptl3), and angiopoietin-like protein 4 (Angptl4). These proteins inhibit the activity of lipoprotein lipase (LPL) and decrease triglyceride metabolism. We believe that inhibiting SREBP activity in the intestine will lead to an increase in LPL enzyme activity, accelerate clearance of triglycerides and substantially reduce both fasting and postprandial triglyceride levels. CAT-2054 is an eicosapentaenoic acid-niacin conjugate. By modulating the SREBP pathway, CAT-2054 may inhibit production of important cholesterol metabolism proteins, such as PCSK9, HMG-CoA reductase, ATP citrate lyase and NPC1L1.
Disease:
Therapeutic area: Metabolic diseases
Country: USA
Trial
details: This is a 2-part, Phase 1, placebo-controlled, double-blind, randomized, single and multiple ascending dose study. CAT-2054 will be administered either as an uncoated capsule (CAT-2054) or a coated capsule (CAT-2054-C). In Part A, CAT-2054 or placebo is administered as a single dose in a fasting state at 4 dose levels; at 3 dose levels, subjects will return for a second dose of the study drug after a high-fat meal. Additionally, at 1 dose level, CAT-2054-C or placebo will be administered as a single dose in a fasting state, and subjects will return for a second dose of the study drug after a high-fat meal. In Part B, CAT-2054 will be administered as multiple ascending doses at 4 dose levels for 14 consecutive days. In selected cohorts, CAT-2054, CAT-2054-C or CAT-2054 with atorvastatin will be dosed to assess safety in anticipation of future clinical trials. (NCT02374047)
Latest
news: * On August 13, 2015, Catabasis Pharmaceuticals, a clinical-stage drug development company built on a pathway pharmacology technology platform, announced positive top-line Phase 1 clinical trial data for CAT-2054, the Company’s product candidate targeting the Sterol Regulatory Element-Binding Protein (SREBP) pathway for the treatment of hypercholesterolemia. CAT-2054 was well-tolerated with no serious adverse events (AEs) observed in either the single or multiple ascending dose arms of the double-blind, randomized clinical trial. In the multiple ascending dose study, decreases in median LDL-C levels of up to 20% were observed at day 21 in healthy volunteers. Importantly, CAT-2054 was also found to be well-tolerated in combination with atorvastatin, the statin drug most commonly used in the treatment of hypercholesterolemia, and there was no evidence for impact of CAT-2054 on the pharmacokinetics of atorvastatin. The Phase 1 clinical trial was designed to assess the safety, tolerability and pharmacokinetics of single and multiple ascending oral doses of CAT-2054 in 118 healthy volunteers. In the single ascending dose portion of the trial, CAT-2054 was well-tolerated and no serious AEs were reported. No safety signals were observed in laboratory, vital sign or electrocardiogram results following CAT-2054 administration. The observed AEs occurring under fed and fasted conditions at doses up to 500 mg were similar for CAT-2054 and placebo. All reported AEs were mild. In the multiple ascending dose portion of the Phase 1 trial, healthy volunteers received CAT-2054 or placebo at total daily doses ranging from 100 to 750 mg given orally once or twice per day for 14 days. CAT-2054 was also given concurrently with atorvastatin in one cohort. CAT-2054 was well-tolerated with no serious AEs reported. No safety signals were observed in laboratory, vital signs or electrocardiogram results following CAT-2054 administration, and all subjects completed dosing. At the highest doses, the most common AEs were GI-related, all of which were mild. CAT-2054 was also well-tolerated with no safety signals in subjects receiving atorvastatin. There was no evidence of clinically significant changes in atorvastatin pharmacokinetics when co-administered with CAT-2054. Catabasis plans to submit the Phase 1 data for presentation at an upcoming medical meeting.
