Juxtapid (lomitapide) / Novelion, Chiesi - LARVOL DELTA

Reduction in lipid accumulation, inflammation and hepatocellular carcinoma development after protease-activated receptor 2 inhibition through 1-Piperidinepropionic acid (EASL 2025) - "Human liver organoids were cultured with different steatogenic conditions (Oleic Acid and SB3) and treated with 1-PPA and lomitapide, an inhibitor of VLDL export... 1-PPA treatment reduced lipid accumulation and M2-macrophage polarization in a mouse model of MASH-induced liver carcinogenesis resulting in lower HCC development. 1-PPA treatment affects lipid accumulation stimulating VLDL secretion."

Hepatocellular Cancer • Hepatology • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease • Oncology • Solid Tumor • ARG2 • MRC1 • SERPINB3 • TNFA

Lomitapide modifies high-density lipoprotein function in homozygous familial hypercholesterolaemia. (PubMed, Eur J Med Res) - P3 | "Our report raises the hypothesis that lomitapide promotes lipidation of HDL particles independently of ABCA1 and ABCG1 through a process involving SR-BI pathway. This effect impairs the total efflux process suggesting that lomitapide drives the reverse cholesterol transport through SR-BI receptors in HoFH patients."

Journal • Dyslipidemia • Familial Hypercholesterolemia • Genetic Disorders • Homozygous Familial Hypercholesterolemia • Metabolic Disorders • ABCA1 • ABCG1

A Case with Oligogenic Familial Hypercholesterolemia Treated by Combination Therapy of Statin, Ezetimibe, PCSK9 Inhibitor, and Lomitapide. (PubMed, Intern Med) - "His LDL-cholesterol level was well controlled by the introduction of a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor and lomitapide (approximately 30 mg/dL). Combination therapy is effective in reducing LDL levels."

Journal • Dyslipidemia • Familial Hypercholesterolemia • Genetic Disorders • Homozygous Familial Hypercholesterolemia • Metabolic Disorders • APOE

Renal Safety Assessment of Lipid-Lowering Drugs: Between Old Certainties and New Questions. (PubMed, Drugs) - "Conventional lipid-lowering therapies (LLTs), such as statins, ezetimibe, and fibrates, can control CKD-associated dyslipidemia and, to some extent, prevent major atherosclerotic events in patients with CKD, but their use in clinical practice presents challenges because of the potential renal safety concerns. In recent years, novel therapies with the ability to lower both low-density lipoprotein cholesterol and triglycerides have been introduced to the market (e.g., proprotein convertase subtilisin/kexin type 9 inhibitors, bempedoic acid, lomitapide, volanesorsen) to improve our ability to control lipid abnormalities...The aim of this review was to examine the renal safety profiles of various LLTs, with special reference to novel medications, and to highlight important considerations and guidance for the use of these medications in overt CKD or in patients with some degree of renal function impairment. We underscore the lack of a comprehensive understanding of kidney..."

Journal • Review • Atherosclerosis • Cardiovascular • Chronic Kidney Disease • Dyslipidemia • Metabolic Disorders • Nephrology • Renal Disease

Ovarian expression of functional MTTP and apoB for VLDL assembly and secretion in chickens. (PubMed, Poult Sci) - "Lomitapide and the ApoB-antisense oligonucleotide Mipomersen dose-dependently decreased MTTP activity and VLDL-apoB secretion from cultured follicular cells, while oleate addition or acute heat stress enhanced VLDL-apoB secretion. Ultrastructural images showed VLDL assembly and trafficking toward the secretion route. The findings support the notion that VLDL assembly and secretion within avian ovarian tissues functions as a protective mechanism against fuel and physical stressors to secure follicle development and/or nutritional quality control of yolk for embryo development."

Journal • Dyslipidemia • APOB

RFWD3 Reprograms Nucleotide Metabolism Through PHGDH to Induce Chemoresistance In Osteosarcoma. (PubMed, Adv Sci (Weinh)) - "Despite the improved knowledge of cancer biology, the core determinants of cisplatin (DDP) resistance in osteosarcoma remain unclear and deserve further exploration. It is found that Lomitapide exhibits a significant synergistic anti-osteosarcoma effect when combined with DDP. In conclusion, a specific role of RFWD3 in regulating nucleotide metabolism is revealed and comprised of targetable candidates for overcoming chemoresistance in osteosarcoma."

Journal • Oncology • Osteosarcoma • Sarcoma • Solid Tumor • Targeted Protein Degradation • PHGDH • RFWD3

High burden of disease in patients with homozygous familial hypercholesterolemia despite recent advances in therapies and updated guidelines: A real-world study. (PubMed, J Clin Lipidol) - "This real-world study showed that patients with HoFH are undertreated, resulting in suboptimal control of LDL-C levels and a high prevalence of ASCVD."

HEOR • Journal • Real-world evidence • Atherosclerosis • Cardiovascular • Coronary Artery Disease • Dyslipidemia • Familial Hypercholesterolemia • Genetic Disorders • Heart Failure • Homozygous Familial Hypercholesterolemia • Metabolic Disorders • Rare Diseases

Integration of 101 machine learning algorithm combinations to unveil m6A/m1A/m5C/m7G-associated prognostic signature in colorectal cancer. (PubMed, Sci Rep) - "Moreover, six drugs (KU-0063794, temozolomide, DNMDP, ML162, SJ-172550, ML050) from the Cancer Therapeutics Response Portal (CTRP) and five drugs (BIBX-1382, lomitapide, ZLN005, PPT, panobinostat) from the PRSM database were identified for the high-risk group patients. Overall, our developed RMS can accurately predict patients survival outcomes and immunotherapy response, indicating promising application in clinical practice. These findings may offer guidance for the prognosis and personalized treatment of CRC."

IO biomarker • Journal • Colorectal Cancer • Gastrointestinal Cancer • Inflammatory Arthritis • Oncology • Solid Tumor

LILITH: Evaluation of the Effect of Lomitapide Treatment on Major Adverse Cardiovascular Events (MACE) in Patients with Homozygous Familial Hypercholesterolemia (clinicaltrials.gov) - P=N/A | N=72 | Recruiting | Sponsor: Fondazione SISA (Societa Italiana per lo Studio della Arteriosclerosi)

Adverse events • New trial • Cardiovascular • Dyslipidemia • Familial Hypercholesterolemia • Genetic Disorders • Homozygous Familial Hypercholesterolemia • Metabolic Disorders • KRT18

Resistance to conventional drug therapy and good response to lomitapide allowed the identification of a novel bi-allelic semi-dominant monogenic HoFH: a case report. (PubMed, Curr Med Res Opin) - "She is now in good clinical condition and laboratory response with lomitapide, evolocumab, statin, and ezetimibe. Lomitapide proved effective in controlling cholesterol levels, highlighting its value in managing complex FH cases. The literature review further emphasizes the critical need for improved diagnostic approaches to minimize the risk of misdiagnosis."

Journal • Cardiovascular • Dyslipidemia • Familial Hypercholesterolemia • Genetic Disorders • Heterozygous Familial Hypercholesterolemia • Homozygous Familial Hypercholesterolemia • Metabolic Disorders • Myocardial Infarction

X-linked ubiquitin-specific peptidase 11 (USP11) increases susceptibility to Cushing's disease in women. (PubMed, Acta Neuropathol Commun) - "Additionally, virtual screening identified Lomitapide and Nicergoline as potential inhibitors of USP11, reducing POMC expression and ACTH secretion. Thus, USP11 emerges as a potential therapeutic target, and drugs aimed at inhibiting its function could benefit women with Cushing's disease."

Journal • Cushing’s Disease • Endocrine Disorders • POMC-null Obesity • Targeted Protein Degradation • USP1 • USP11

Binding of Selected Ligands to Human Protein Disulfide Isomerase and Microsomal Triglyceride Transfer Protein Complex and the Associated Conformational Changes: A Computational Molecular Modelling Study. (PubMed, ChemistryOpen) - "In the present study, the conformational changes of the MTP complex upon the binding of three selected small-molecule ligands (17β-estradiol, lomitapide and a phospholipid) are investigated based on the available biochemical and structural information by using the protein-ligand docking method and molecular dynamics (MD) simulation...It will be of interest to further explore whether the binding of small molecules can facilitate the conformational transitions of PDI in the future. The molecular and structural insights gained from the present work are of value for understanding some of the important biological functions of PDI and the MTP complex."

Journal • Cardiovascular

Preclinical evaluation of new drug-drug interactions of lomitapide: A proposal for novel mechanism of interaction associated with lipid metabolic changes. (PubMed, Biochem Pharmacol) - "Repeated administration of lomitapide decreased the serum lipid levels and VLDL/LDL-philic drug concentrations, to 20% for amiodarone, to 52% for doxycycline, and to 62% for tetracycline. Collectively, through a series of experiments, we revealed the association between drugs and VLDL/LDL, and their impact on pharmacokinetics. Our study suggested that lomitapide decreases serum concentrations of VLDL/LDL-philic drugs probably due to changes in their absorption kinetics, proposing novel drug-drug interactions associated with lipid metabolic changes."

Journal • Preclinical • Dyslipidemia

Laboratory-Engineered Glioblastoma Organoid Culture and Drug Screening. (PubMed, J Vis Exp) - "In this context, we present an advanced human GBM organoid model, the Laboratory Engineered Glioblastoma Organoid (LEGO), and illustrate its use in studying the genotype-phenotype dependencies and screening potential drugs for GBM. Utilizing this model, we have identified lipid metabolism dysregulation as a critical milestone in GBM progression and discovered that the microsomal triglyceride transfer protein inhibitor Lomitapide shows promise as a potential treatment for GBM."

Journal • Preclinical • Brain Cancer • CNS Tumor • Glioblastoma • Metabolic Disorders • Oncology • Solid Tumor

New insights into the management of homozygous familial hypercholesterolemia patients treated with lomitapide: a single-center experience. (PubMed, Front Endocrinol (Lausanne)) - "Besides statins, ezetimibe and PCSK9 inhibitors, lomitapide (an anti-ApoB therapy) was also approved in 2012-2013 as an adjunctive treatment for HoFH. In this context, we decided to report the main available evidence on the management and monitoring of HoFH patients treated with lomitapide and to accompany this literature review with a description of our clinical experience with a subset of six HoFH patients. In conclusion, this paper aims to address an important topic for HoFH-related clinical practice that, to our knowledge, is not yet formally regulated by proper national and/or international guidelines."

Journal • Review • Cardiovascular • Dyslipidemia • Familial Hypercholesterolemia • Gastrointestinal Disorder • Genetic Disorders • Homozygous Familial Hypercholesterolemia • Metabolic Disorders • APOB

Management of a young HoFH patient during pregnancy using Lipoprotein Apheresis (whole blood): A novel experience. (PubMed, Transfus Apher Sci) - "We present a 31-year-old Caucasian pregnant woman with HoFH clinical phenotype on lipid-lowering treatment with Lomitapide and Evolocumab, discontinued during pregnancy. LA with dextran sulfate has been an effective and safe choice for the mother and fetus. Furthermore it was reasonably well tolerated from the beginning of pregnancy management to its conclusion."

Journal • Cardiovascular • Dyslipidemia • Familial Hypercholesterolemia • Genetic Disorders • Homozygous Familial Hypercholesterolemia • Metabolic Disorders

Sex-related differences in response to lomitapide in HoFH: A subanalysis of the Pan-European Lomitapide retrospective observational study. (PubMed, Atherosclerosis) - "Lomitapide demonstrates comparable efficacy in reducing LDL-C levels in men and women with HoFH, with potential sex-specific variations in tolerability."

Journal • Observational data • Retrospective data • Atherosclerosis • Cardiovascular • Dyslipidemia • Familial Hypercholesterolemia • Gastrointestinal Disorder • Genetic Disorders • Homozygous Familial Hypercholesterolemia • Metabolic Disorders

Computational approach towards repurposing of FDA approved drug molecules: strategy to combat antibiotic resistance conferred by Pseudomonas aeruginosa. (PubMed, J Biomol Struct Dyn) - "Also, Lomitapide and Venetoclax showed low bioavailability scores, while Nilotinib, Eltrombopag, and Conivaptan demonstrated higher potential for therapeutic levels. The RMSD, RMSF, Hydrogen bond formation, Radius of gyration, SASA, PCA, DCCM, DSSP and MM-PBSA binding energy calculation along with demonstrated high stability of the MexB-Nilotinib complex with lesser distortions. Our study concludes, that Nilotinib is a potential inhibitor and can be developed as a therapeutic agent against MexB protein for controlling P. aeruginosa infections."

FDA event • Journal • Cystic Fibrosis • Dermatitis • Dermatology • Genetic Disorders • Immunology • Infectious Disease • Nephrology • Pulmonary Disease • Respiratory Diseases

Familial Hypercholesterolemia in Saudi Arabia: Clinical Characteristics and Mortality Rate (ESPE 2024) - "Management included lifestyle changes for all patients (100.0%), liver transplants (23.8%) (stopped all medical therapy after transplant), LDL apheresis (36.9%), 10 patients are on Lomitapide and all were on statins and ezetimibe. This study highlights the severe impact of FH in Saudi Arabia, emphasizing the need for early detection and comprehensive management. The findings underscore the importance of genetic screening, personalized treatment, and proactive family engagement to reduce cardiovascular risks associated with FH. Enhanced public health strategies and healthcare interventions are essential to improve outcomes for FH patients in the region."

Clinical • Late-breaking abstract • Atherosclerosis • Cardiovascular • Dyslipidemia • Familial Hypercholesterolemia • Genetic Disorders • Heart Failure • Hepatology • Homozygous Familial Hypercholesterolemia • Metabolic Disorders

Homozygous familial hypercholesterolemia in Spain. Data from Registry of the Spanish Atherosclerosis Society. (PubMed, J Clin Endocrinol Metab) - "The current situation of HoFH in Spain is better than expected, with marked reductions in LDLc levels with new treatments. In this population, recommended LDLc goals are difficult to achieve despite maximum lipid-lowering therapy. ASCVD has been reduced and delayed by two decades."

Journal • Atherosclerosis • Cardiovascular • Dyslipidemia • Familial Hypercholesterolemia • Genetic Disorders • Homozygous Familial Hypercholesterolemia • Metabolic Disorders • Rare Diseases • APOB

A Budget Impact Analysis of a New Treatment for Adults With Homozygous Familial Hypercholesterolaemia (ISPOR-EU 2024) - "HoFH patients who do not reach their LDL-C goal on lipid lowering therapies (e.g., statins, ezetimibe, apheresis, PCSK9 inhibitors) are eligible for additional treatment with lomitapide...A new scenario with evinacumab estimated the costs if 5% of lomitapide-eligible patients receive evinacumab each year instead... Introduction of a new treatment into NHS England will affect the total costs for treating adults with HoFH compared with current SoC. This should be a consideration when appraising the value of new technologies for the management of HoFH."

Clinical • HEOR • Atherosclerosis • Cardiovascular • Dyslipidemia • Familial Hypercholesterolemia • Homozygous Familial Hypercholesterolemia

Lomitapide: navigating cardiovascular challenges with innovative therapies. (PubMed, Mol Biol Rep) - "Glob Health Med, Efficacy and safety of saroglitazar for the management of dyslipidemia: A systematic review and meta-analysis of interventional studies. Lowering LDL-C levels is important for preventing atherosclerosis, reducing cardiovascular risk, improving endothelial function, and promoting overall cardiovascular health, especially for patients with HoFH Efficacy and safety of a microsomal triglyceride transfer protein inhibitor in patients with homozygous familial hypercholesterolaemia: a single-arm, open-label, phase 3 study. This review paper focuses on research findings regarding the therapeutic benefits of lomitapide, highlighting its effectiveness in lowering cholesterol levels and reducing the risk of CVDs The microsomal triglyceride transfer protein inhibitor lomitapide improves vascular function in mice with obesity."

Journal • Review • Atherosclerosis • Cardiovascular • Dyslipidemia • Familial Hypercholesterolemia • Genetic Disorders • Homozygous Familial Hypercholesterolemia • Metabolic Disorders • Myocardial Infarction • Obesity • APOB

Lomitapide for the treatment of paediatric patients with homozygous familial hypercholesterolaemia (APH-19): results from the efficacy phase of an open-label, multicentre, phase 3 study. (PubMed, Lancet Diabetes Endocrinol) - P3 | "Lomitapide provided a significant, clinically meaningful LDL cholesterol reduction and has the potential to be an efficient, LDL receptor-independent option for paediatric patients with HoFH."

Journal • P3 data • Atherosclerosis • Cardiovascular • Dyslipidemia • Familial Hypercholesterolemia • Gastrointestinal Disorder • Genetic Disorders • Homozygous Familial Hypercholesterolemia • Pediatrics • APOB

Lomitapide for the treatment of homozygous familial hypercholesterolaemia in children. (PubMed, Lancet Diabetes Endocrinol) - No abstract available

Journal • Dyslipidemia • Familial Hypercholesterolemia

Regulation of lipid and serine metabolism by the oncogene c-Myc. (PubMed, Int Rev Cell Mol Biol) - "Here, we report that c-Myc can activate both lipid and serine metabolism against the backdrop of tumor formation, and different therapies like aspirin and lomitapide target the links between c-Myc and metabolism to slow down tumor progression and invasion. Finally, we also summarize the existing knowledge on the involvement of epigenetic pathways and non-coding RNAs in regulating lipid and serine metabolism and c-Myc in tumor cells. Identification of non-coding factors and epigenetic mechanisms present a promising avenue of study that could empower researchers with novel anticancer treatment targeting c-Myc and lipid and serine metabolism pathways!"

Journal • Review • Metabolic Disorders • Oncology • LEP • MYC