gemcabene (CI-1027) / Beijing SL Pharma, Dong-A - LARVOL DELTA

A Systematic Review of the Randomized Controlled Trials of Gemcabene and Its Therapeutic Uses. (PubMed, Cureus) - "The study concluded that gemcabene was effective as an anti-inflammatory agent and reduced lipid levels and the progression of fibrosis. Hence, further controlled trials are needed to determine its efficacy and safety in human subjects, along with the identification of adverse effects."

Journal • Review • Fibrosis • Immunology

NeuroBo Pharmaceuticals Receives Approval for Amendment of Contingent Value Rights for Gemcabene (PRNewswire) - "NeuroBo Pharmaceuticals, Inc....today announced that it has received approval of an amendment to its Contingent Value Rights (CVR) agreement from a majority of the holders of a majority of the outstanding CVRs, incentivizing the evaluation of Gemcabene as a treatment for COVID-19....'We intend to evaluate Gemcabene both as a stand-alone treatment for COVID-19, and in a treatment combination with ANA001'...'We look forward to achieving multiple value-creating milestones in the coming year, including the data monitoring committee results, the pharmacokinetic (PK) data for the phase 2 trial of ANA001, the top-line data readout from the phase 2 trial of ANA001 to treat COVID-19 and preclinical in vitro data for Gemcabene against COVID-19 variants alone and in treatment combination with ANA001.'"

Licensing / partnership • P2 data • PK/PD data • Preclinical • Infectious Disease • Novel Coronavirus Disease

"$NRBO NeuroBo Pharmaceuticals Receives Approval for Amendment of Contingent Value Rights for Gemcabene https://t.co/Byv7KoDpTF" (@stock_titan)

Gemcabene for the Treatment of Pediatric NAFLD (clinicaltrials.gov) - P2a; N=6; Terminated; Sponsor: Emory University; Completed ➔ Terminated; Terminated due to lack of efficacy and safety concerns.

Clinical • Trial termination • Hepatology • Non-alcoholic Fatty Liver Disease • Pediatrics • APOA1 • APOB • APOE • CRP • IL1B • IL6

[VIRTUAL] An Open-Label Study of Gemcabene in Adults with Familial Partial Lipodystrophy (ADA 2020) - "This limited proof-of-concept study provided evidence that gemcabene has the potential to lower triglycerides in certain FPLD patients at 12 weeks. Heterogeneous patient responses observed in this study might be related to different genetic etiologies; however further studies are needed to understand this phenomenon."

Clinical • Lipodystrophy • Metabolic Disorders • LMNA

Gemcabene Effect in a Phase 2b Study in Hypercholesterolemic Subjects Not Adequately Controlled on High-Intensity or Moderate-Intensity Stable Statin Therapy (ROYAL-1) (ESC 2017) - No abstract available.

Clinical • P2 data • Cardiovascular

"Famous soap opera with gemcabene. It was a torture 😬" (@InsiderBiotech)

Emerging lipid lowering agents targeting LDL cholesterol. (PubMed, Postgrad Med) - "LDL-C lowering agents (statins, ezetimibe and PCSK9 inhibitors) reduce cardiovascular risk in primary and secondary prevention proportionally to LDL-C reduction (23% per 1 mmol/L of LDL). This has prompted the development of new LDL-C lowering drugs in the hope to reduce cardiovascular risk, such as bempedoic acid, inclisiran, gemcabene and evinacumab. Drugs targeting other lipids (triglycerides, HDL-C, lipoprotein (a)), intravascular inflammation or acting by other mechanisms also have a role in atherosclerosis prevention, however, they will not be covered in this review."

Journal

Usefulness of Gemcabene in Homozygous Familial Hypercholesterolemia (from COBALT-1). (PubMed, Am J Cardiol) - "Depending on residual LDL receptor (LDLR) function, most HoFH patients respond modestly to statins, ezetimibe, and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors. Mean change from baseline in LDL-C was -26% (p = 0.004) at Week 4 (300 mg), -30% (p = 0.001) at Week 8 (600 mg), and -29% (p = 0.001) at Week 12 (900 mg). In conclusion, the COBALT-1 study demonstrates gemcabene has potential to significantly reduce LDL-C levels when used as an adjunctive therapy to current lipid-lowering treatment for familial hypercholesterolemia patients."

Journal

Pharmacokinetics of current and emerging treatments for hypercholesterolemia. (PubMed, Expert Opin Drug Metab Toxicol) - "Ezetimibe, icosapent ethyl and the monoclonal antibodies evolocumab and alirocumab have established efficacy and safety. Newer oral agents including pemafibrate and bempedoic acid have generally favorable pharmacokinetics supporting use in a wide range of patients. RNA-based therapies with antisense oligonucleotides are highly specific for their targets and those inhibiting apoB, apoCIII, angiopoietin-like protein 3 and lipoprotein(a) have shown promising results. The small-interfering RNA inclisiran has the notable advantage that a single subcutaneous administration may be effective for up to 6 months. The CV outcome trial results and long term safety data are eagerly awaited for these new agents."

Journal • PK/PD data

INDIGO-1: A 12-Week Study to Assess the Efficacy Safety and Tolerability of Gemcabene in Subjects With Severe Hypertriglyceridemia (clinicaltrials.gov) - P2; N=91; Completed; Sponsor: NeuroBo Pharmaceuticals Inc.; Active, not recruiting ➔ Completed

Clinical • Trial completion

Lipid-Lowering Agents. (PubMed, Circ Res) - "Lomitapide, mipomersen, AAV8.TBG.hLDLR, inclisiran, bempedoic acid, and gemcabene primarily target LDL cholesterol. Alipogene tiparvovec, pradigastat, and volanesorsen primarily target elevated triglycerides, whereas evinacumab and IONIS-ANGPTL3-L target both LDL cholesterol and triglyceride. IONIS-APO(a)-L targets Lp(a)."

Journal

Gemcabene for the Treatment of Pediatric NAFLD (clinicaltrials.gov) - P2a; N=6; Completed; Sponsor: Emory University; Active, not recruiting ➔ Completed; N=40 ➔ 6

Clinical • Enrollment change • Trial completion

Gemphire Therapeutics shares soar on optimistic phase 2b trial results for gemcabene (Proactiveinvestors) - "Shares of Gemphire Therapeutics...rocketed in pre-market trade Friday after the clinical-stage biopharmaceutical group reported rosy results from a Phase 2b trial assessing how well its drug gemcabene treats patients with severe hypertriglyceridemia...Gemphire shares jumped 146% to US$12.89 in response to the good news."

P2b data • Stock price

Study of Gemcabene in Adults With FPLD (clinicaltrials.gov) - P1/2; N=5; Completed; Sponsor: Elif Oral; Active, not recruiting ➔ Completed; Trial completion date: Jun 2020 ➔ Jul 2019

Clinical • Trial completion • Trial completion date

Gemphire Therapeutics and NeuroBo Pharmaceuticals Announce Merger Agreement to Advance a Neurodegenerative Disease Company (GlobeNewswire, Gemphire Therapeutics Inc.) - Today, Gemphire also announced that the company has signed an out-licensing partnership with Beijing SL Pharmaceutical Co. Ltd. to advance its drug candidate, gemcabene, into the Chinese market. This partnership is expected to provide an upfront gross payment of $2.5 million to Gemphire and back end milestone and royalty payments to the combined company if certain development and commercialization milestones are met.

Clinical • Commercial

Comparative Evaluation of Gemcabene and PPAR Ligands in Transcriptional Assays of Peroxisome Proliferator-Activated Receptors: Implication for the Treatment of Hyperlipidemia and Cardiovascular Disease. (PubMed, J Cardiovasc Pharmacol) - "...Surprisingly, gemcabene showed no or little PPAR-α transactivation compared with reference agonists, which showed concentration-dependent transactivation against human PPAR-α of 2.4- to 30-fold (fenofibric acid), 17-fold (GW590735), and 2.3- to 25-fold (WY-14643)...By contrast, the known agonists, rosiglitazone, indomethacin, and muraglitazar showed strong activation against the mouse, rat, and human PPAR-γ receptors...These data suggest that the peroxisomal effects observed in rodents and the lipid regulating effects observed in rodents and humans are not related to a direct activation of PPAR receptors by gemcabene.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal."

Journal

Recent advances in synthetic pharmacotherapies for dyslipidaemias. (PubMed, Eur J Prev Cardiol) - "...For hypercholesterolaemia, pitavastatin provides a very low dose and potent statin that does not adversely affect glucose metabolism; bempedoic acid acts at a biochemical step preceding hydroxymethylglutaryl-CoA reductase and is not associated with muscular side effects. For hypertriglyceridaemia, pemafibrate displays a unique and selective agonist activity on peroxisomal proliferator activated receptor-α that does not elevate homocysteine or creatinine...Gemcabene, a dicarboxylic acid regulating apolipoprotein B-100, is effective in reducing both cholesterol and triglycerides. Among cholesteryl ester transfer protein antagonists that elevate HDL-C, only anacetrapib reduces cardiovascular events. Probucol stimulates reverse cholesteryl ester transport, lowers LDL-C stabilizing plaques and may lower incidence of cardiovascular events. These agents, which act through novel mechanisms, afford good and potentially safe treatment choices that may increase adherence and the..."

Journal

Study of Gemcabene in Adults With FPLD (clinicaltrials.gov) - P1/2; N=5; Active, not recruiting; Sponsor: Elif Oral; Trial completion date: Mar 2020 ➔ Jun 2020

Clinical • Trial completion date

Study of Gemcabene in Adults With FPLD (clinicaltrials.gov) - P1/2; N=5; Active, not recruiting; Sponsor: Elif Oral; Recruiting ➔ Active, not recruiting; Trial primary completion date: Mar 2020 ➔ May 2019

Clinical • Enrollment closed • Trial primary completion date