Juxtapid (lomitapide) / Novelion, Chiesi - LARVOL DELTA

MEGF8-mediated GDF8 phosphorylation drives TGF-β hyperactivation in osteoarthritis cartilage degeneration: Mechanism and targeted intervention. (PubMed, Life Sci) - "Virtual screening identified small molecular compounds, including Conivaptan, Noxafil, and Lomitapide, that targeted the complex interface and formed stable conformations with the protein complex, significantly inhibiting the pathological progression of OA. The MEGF8-GDF8-ACVR2B complex is a key switch for TGF-β hyperactivation in OA, and a drug repurposing strategy targeting this interface offers a new direction for the disease-modifying treatment of OA."

Journal • Immunology • Osteoarthritis • Pain • Rheumatology • ACVR2B • EGF • MEGF8 • MMP2 • MMP9 • SMAD2 • TGFB1

Heat stress enhances VLDL secretion in chicken ovarian follicles to potentiate its impact on follicular cell survival and maturation. (PubMed, Poult Sci) - "HS (42°C) for 8 hr (HS8H) or HS3H and following recovery at 37°C to 16 hr (3H13R) upregulated PCNA and/or IL-1β expressions in granulosa (GC) and theca (TH) cells and augmented progesterone (P4) and estradiol (E2) production, respectively. Surprisingly, Lomitapide and Mipomersen rescued TH cell viability at HS8H and 8H8R in association with alleviated lipid, MDA, and ROS accumulations, whereas GCs exhibited improved viability at HS8H, but not at 8H8R and 3H13R in couple with worse depletion of neutral lipids and cholesterol, suggesting that HS operates at VLDL production to alter cellular lipid dynamics to potentiate cell death, while TH cells are more thermoresistant due to a proficient adaption in lipid disposal. In conclusion, HS enhances VLDL production in hierarchical follicles to augment its impacts on follicular cell fate, but routine secretion of VLDL is obligatory to sustain follicle maturation under normal conditions, in which TH cells are highly..."

Journal • IL1B • PCNA

Long-term efficacy and safety of lomitapide in patients with familial chylomicronemia syndrome: Data from an expanded access program. (PubMed, J Clin Lipidol) - P3 | "Lomitapide effectively and safely reduced TG levels in FCS patients with a history of pancreatitis over a nearly 3-year follow-up period. These findings are consistent with those of the open-label trial, despite the use of a lower median daily dose (27 mg). No new safety signals were observed."

Journal • Dyslipidemia • Familial Chylomicronemia Syndrome • Familial Hypercholesterolemia • Genetic Disorders • Homozygous Familial Hypercholesterolemia • Metabolic Disorders • Pancreatitis

A real-world analysis of Lomitapide-associated adverse events: Data from FAERS and CVAROD. (PubMed, Medicine (Baltimore)) - "The early onset of reactions and emergence of novel signals highlight the importance of close monitoring, particularly during treatment initiation. Personalized risk mitigation strategies should be implemented to optimize the safety of Lomitapide therapy in HoFH patients."

Adverse events • Journal • Real-world evidence • Dyslipidemia • Familial Hypercholesterolemia • Genetic Disorders • Hematological Disorders • Homozygous Familial Hypercholesterolemia • Metabolic Disorders • Pain • Pediatrics

Breakthrough LDL-C reduction in a patient with autosomal recessive homozygous familial hypercholesterolemia: Efficacy of evinacumab after LDL-apheresis discontinuation. (PubMed, J Clin Lipidol) - "The introduction of evinacumab, an LDL receptor-independent lipid-lowering therapy, achieved robust and sustained LDL-C reduction, while eliminating the need for LDL-apheresis and reducing the indirect logistical burden of frequent hospital-based treatments in this patient with AR-HoFH."

Journal • Atherosclerosis • Cardiovascular • Coronary Artery Disease • Dyslipidemia • Familial Hypercholesterolemia • Genetic Disorders • Hematological Disorders • Homozygous Familial Hypercholesterolemia • Metabolic Disorders • Myocardial Infarction

PORTRAIT Survey: Patient-Centered Overview Related to Treatment Practices in Lipoprotein Apheresis: Italian Investigating Trajectories. (PubMed, Ther Apher Dial) - "The PORTRAIT survey would like to promote a network to better manage the patients on chronic LA."

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

Lessons from recent clinical trials for the prevention of acute pancreatitis in chylomicronemia syndromes. (PubMed, Curr Opin Endocrinol Diabetes Obes) - "These emerging mechanism-based therapies are reshaping the management of severe hypertriglyceridemia, offering targeted approaches to reduce triglycerides and acute pancreatitis risk. Ongoing studies will clarify long-term safety, durability of response, and optimal patient selection, providing a framework for improved clinical outcomes."

Journal • Dyslipidemia • Hepatology • Hypertriglyceridemia • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • Pancreatitis • Severe Hypertriglyceridemia • ANGPTL3 • FGF21 • LPL

A high-throughput screening approach to discover potential colorectal cancer chemotherapeutics: repurposing drugs to identify novel disruptors of 14-3-3 proteins. (PubMed, Cell Death Dis) - "Terfenadine, penfluridol, and lomitapide have potential to either be repurposed as chemotherapeutics, or more likely, used as starting points for novel lead development. The described assay cascade demonstrates the feasibility of both expanding on these compounds and identifying novel disruptors of 14-3-3ζ to develop pro-apoptotic agents to treat pathogenic aberrant cell growth."

Journal • Colorectal Cancer • Oncology • Solid Tumor • BCL2

Severe Hypertriglyceridemia in Pregnancy: A Case Highlighting Therapeutic Challenges (AHA 2025) - "Prior to conception, she had been treated with a biguanide for diabetes and a combination of fish oil, fenofibrate, and a statin for HTG, which were discontinued for fetal safety. Given the markedly elevated TG level, a multidisciplinary decision was made to urgently reinitiate lipid-lowering therapy with omega-3 acid ethyl esters 4g daily (Lovaza) and subcutaneous insulin glargine...Traditional lipid-lowering agents, including statins, PCSK9 inhibitors, ezetimibe, bempedoic acid, and lomitapide, are generally avoided during pregnancy due to limited fetal safety data...Thus, cardio-obstetric management of high-risk women with metabolic disorders should center around preconception risk assessment, multidisciplinary care, intensive lifestyle modification, selective use of non-statin agents or apheresis, and vigilant monitoring throughout pregnancy. There remains a significant gap in evidence regarding the safety and efficacy of lipid-lowering therapies during pregnancy,..."

Clinical • Diabetes • Dyslipidemia • Gynecology • Hypertriglyceridemia • Obstetrics • Pancreatitis • Severe Hypertriglyceridemia • Type 2 Diabetes Mellitus

Selective Degradation of Excess Free Cholesterol in the Liver by REP-0003 Regresses Atherosclerotic Plaque in Ldlr -/- Mice: A Novel Approach for HoFH (AHA 2025) - "In HoFH patients, statins and PCSK9 inhibitors are ineffective and, while new lipid-lowering therapies including angiopoietin-like 3 inhibitors and lomitapide offer hope, they have not been shown to effectively regress existing plaque, highlighting a critical unmet medical need...At euthanasia, tissues and blood were harvested and assessed for blood chemistries, serum biomarkers, atherosclerotic plaque burden, and histopathology.ResultsCompared with PBS, REP-0003 treatment significantly reduced serum alanine transaminase (ALT) levels by 40.5 ± 3.7% (P<0.01, indicating improved liver health), reduced serum ApoB levels by 23.9 ± 1.0% (P<0.01) and increased HDL free cholesterol fraction by 61.2 ± 5.8% (P<0.01). Versus controls, (a) aortic root plaque cross-sectional area and aortic tree plaque count/area were significantly reduced by 27.2 ± 4.8% (P<0.01) and 25.8 ± 1.8% (P<0.05), respectively, (b) plaque macrophage infiltration via..."

Preclinical • Atherosclerosis • Dyslipidemia • Genetic Disorders • Homozygous Familial Hypercholesterolemia • ANGPTL3 • APOB • CD68 • LDLR

Functional MTTP and apoB for VLDL secretion in chicken ovaries support small follicle development under heat stress. (PubMed, J Therm Biol) - "Lomitapide and Mipomersen augmented lipid accumulation, oxidative stress, inflammatory response, and exacerbated transient impairment of estradiol secretion and cell proliferation in SYFs under 3 h HS and after recovery, but failed to rescue cell viability despite relieved ER and proteostatic stress. In conclusion, routine secretion of VLDL by SYFs serves as an intrinsic mechanism to sustain cell viability and functions to support the whole program required for follicle development, while under HS, this mechanism provisionally rescues steroidogenesis and cell proliferation."

Journal • Inflammation • Targeted Protein Degradation • APOB • CASP3 • CASP7 • IL1B

Breaking barriers: Innovative therapies for managing homozygous familial hypercholesterolemia. (PubMed, Exp Mol Pathol) - "Recent advancements have introduced novel pharmacological agents for treating HoFH (e.g. evolocumab, alirocumab, inclisiran and bempedoic acid), including cholesterol-lowering strategies that function independently of LDL-R such as lomitapide and evinacumab offering significant promise for managing this condition. However, disparities in the treatment of HoFH persist across different regions and countries. In this context, the review provides a comprehensive overview of established treatment modalities and emerging therapeutic agents for individuals with HoFH."

Journal • Review • Atherosclerosis • Cardiovascular • Dyslipidemia • Familial Hypercholesterolemia • Genetic Disorders • Homozygous Familial Hypercholesterolemia • Metabolic Disorders • Transplantation

Contemporary Management of Familial and Multifactorial Chylomicronemia Syndromes in Italy: Insights From the National Lipigen Registry. (PubMed, Arterioscler Thromb Vasc Biol) - "As compared with MCS, patients with FCS showed a more severe phenotype and higher prevalence of LPL variants. Lomitapide and volanesorsen provide better triglyceride control, yet only one-third of FCS were treated with these drugs in the routine clinical practice."

Journal • Atherosclerosis • Cardiovascular • Dyslipidemia • Familial Chylomicronemia Syndrome • Hypertriglyceridemia • Pancreatitis • Severe Hypertriglyceridemia • APOA5

Lomitapide response in a cohort of patients with homozygous familial hypercholesterolemia and the potential influence of MTTP gene variants. (PubMed, Orphanet J Rare Dis) - "This study builds upon previous findings by our group suggesting that variants in the MTTP gene may influence response to lomitapide. This study further presented a number of variants that may be uniquely associated with higher or lower response to lomitapide treatment."

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

Lomitapide enhances cytotoxic effects of temozolomide in chemotherapy-resistant glioblastoma. (PubMed, JCI Insight) - "Concomitant treatment with lomitapide and temozolomide (TMZ) prolonged survival and delayed tumor recurrence in a mouse glioblastoma model, compared with treatment xwith TMZ alone. Our data identified lomitapide as a potential adjunct for treatment of temozolomide-resistant glioblastoma."

Journal • Brain Cancer • Glioblastoma • Glioma • Oncology • Solid Tumor

A Comprehensive Review of the Latest Approaches to Managing Hypercholesterolemia: A Comparative Analysis of Conventional and Novel Treatments: Part II. (PubMed, Pharmaceuticals (Basel)) - "It also examined non-pharmacological interventions and conventional therapies, with a detailed focus on statins and ezetimibe...It explores the mechanisms, clinical applications, safety profiles, and pharmacogenetic aspects of novel agents such as proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors (alirocumab, evolocumab), small interfering RNA (siRNA) therapy (inclisiran), adenosine triphosphate-citrate lyase (ACL) inhibitor (bempedoic acid), microsomal triglyceride transfer protein (MTP) inhibitor (lomitapide), and angiopoietin-like protein 3 (ANGPTL3) inhibitor (evinacumab). These agents offer targeted strategies for patients with high residual cardiovascular risk, familial hypercholesterolemia (FH), or statin intolerance. By integrating the latest advances in precision medicine, this review underscores the expanding therapeutic landscape in dyslipidemia management and the evolving potential for individualized care."

Journal • Review • Atherosclerosis • Cardiovascular • Dyslipidemia • Familial Hypercholesterolemia • Genetic Disorders • Metabolic Disorders • ANGPTL3

Identification of key modules and hub genes for sepsis-induced myopathy using weighted gene co-expression network analysis. (PubMed, Front Genet) - "Additionally, leveraging the Connectivity Map (CMAP) database allowed us to predict six potential pharmacological agents-halcinonide, lomitapide, TG-101348, GSK-690693, loteprednol, and indacaterol-that might serve as therapeutic interventions for SIM. This research advances our understanding of the molecular basis of SIM, presenting new diagnostic biomarkers and potential drug targets. Further studies with larger clinical datasets are warranted to validate these findings and explore the therapeutic potential of the identified drugs."

Journal • Infectious Disease • Inflammation • Myositis • Septic Shock • CXCL10 • IL6 • STAT1

Multimodal Therapy Achieves Secondary Prevention LDL-C Targets in LDL-Receptor Null Homozygous Familial Hypercholesterolemia. (PubMed, JACC Case Rep) - "Effective treatment of homozygous familial hypercholesterolemia requires multimodal lipid-lowering therapies. With currently available treatments it is possible to achieve previously unattainable lowering of LDL-C to prevent vascular disease and the need for liver transplantation."

Journal • Cardiovascular • Coronary Artery Disease • Dyslipidemia • Familial Hypercholesterolemia • Genetic Disorders • Heart Failure • Homozygous Familial Hypercholesterolemia • Metabolic Disorders • Transplantation

Lomitapide, a Microsomal Triglyceride Transfer Protein Inhibitor, in Homozygous Familial Hypercholesterolemia: A Systematic Review and Meta-Analysis of Efficacy and Safety. (PubMed, Cardiovasc Drugs Ther) - "Lomitapide demonstrates substantial efficacy in reducing LDL-C and other atherogenic lipids in HoFH patients, with an acceptable safety profile. These findings support its role as an adjunctive therapy in this population, though further randomized controlled trials are warranted to validate long-term safety and effectiveness."

Journal • Retrospective data • Review • Atherosclerosis • Cardiovascular • Dyslipidemia • Familial Hypercholesterolemia • Genetic Disorders • Homozygous Familial Hypercholesterolemia • Metabolic Disorders • Pediatrics • APOB

Dyslipidemias as rare diseases. (PubMed, Cas Lek Cesk) - "Thanks to new hypolipidemic drugs such as evinacumab and lomitapide, patients today have a much better prognosis than in the past...Due to new causal metreleptine therapy, we can help patients with managing these metabolic complications significantly...Therapy with volanesorsen leads to a reduction of hypertriglyceridemia, thereby reducing the risk of developing acute pancreatitis. Although these diseases are rare, it is necessary to think about them and diagnose them early. Interdisciplinary cooperation is essential during search and treatment of these patients."

Journal • Atherosclerosis • Cardiovascular • Dyslipidemia • Familial Hypercholesterolemia • Homozygous Familial Hypercholesterolemia • Hypertriglyceridemia • Lipodystrophy • Metabolic Disorders • Pancreatitis • Rare Diseases

Lomitapide for the treatment of pediatric homozygous familial hypercholesterolemia. (PubMed, Expert Opin Pharmacother) - "Safety and tolerability studies are consistent with the known mechanism of lomitapide on the gastrointestinal and hepatic systems, being generally mild and manageable in pediatric patients with HoFH. The results of longer-term safety data are awaited."

Journal • Review • Atherosclerosis • Cardiovascular • Dyslipidemia • Familial Hypercholesterolemia • Genetic Disorders • Homozygous Familial Hypercholesterolemia • Metabolic Disorders • Pediatrics

Liver transplantation for homozygous familial hypercholesterolaemia. (PubMed, Curr Opin Lipidol) - "Liver transplantation provides a more effective means of lowering LDL than currently available alternatives such as apheresis and lomitapide but carries with it an unacceptably high risk of posttransplant morbidity and mortality. This is mainly due to the adverse effects of life-long immunosuppressive drug therapy, which restricts the use of liver transplantation to those HoFH patients in whom optimal medical therapy has failed."

Journal • Cardiovascular • Dyslipidemia • Familial Hypercholesterolemia • Hepatology • Homozygous Familial Hypercholesterolemia • Transplantation

Role of S-palmitoylation in digestive system diseases. (PubMed, Cell Death Discov) - "Decades of investigations have driven the development of a large body of inhibitors targeting zDHHCs and depalmitoylases, such as S-(2-acetamidoethyl) 2-bromohexadecanethioate (MY-D-4), Artemisinin and Lomitapide. This review provides a comprehensive summary of the role of palmitoylation in digestive system diseases, discusses its effect on disease mechanisms. By elucidating the regulatory functions of palmitoylation under these conditions, this review aimed to identify new strategies for the diagnosis and treatment of digestive system disorders."

Journal • Review • Gastroenterology • Gastrointestinal Cancer • Gastrointestinal Disorder • Hepatology • Immunology • Inflammatory Bowel Disease • Metabolic Disorders • Oncology • Solid Tumor

MTP Restricts Steroidogenesis in Leydig Cells by Regulating Srebp2 (ENDO 2025) - "Inhibition of the MTP activity by lomitapide and sgRNA mediated knockdown significantly increased progesterone secretion in mouse Leydig MA10 cells after stimulation with cyclic AMP. In short, these studies identify a negative regulatory role of MTP in steroidogenesis and show that MTP regulates steroidogenesis in Leydig cells by modulating the expression and activity of Srebp2. Inhibition of testicular MTP might be useful to treat hypogonadism in some patients."

Endocrine Disorders • Genetic Disorders • Obesity • APOB

SRSF7 promotes pulmonary fibrosis through regulating PKM alternative splicing in lung fibroblasts. (PubMed, Acta Pharm Sin B) - "In this study, we identified an up-regulation of serine/arginine-rich splicing factor 7 (SRSF7) in lung fibroblasts derived from IPF patients and a bleomycin (BLM)-induced mouse model, and further characterized its functional role in both human fetal lung fibroblasts and mice. Importantly, through drug screening, we identified lomitapide as a novel modulator of SRSF7, which effectively mitigated experimental pulmonary fibrosis. Collectively, our findings elucidate a molecular pathway by which SRSF7 drives fibroblast metabolic dysregulation and propose a potential therapeutic strategy for pulmonary fibrosis."

Journal • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Interstitial Lung Disease • Metabolic Disorders • Pulmonary Disease • Respiratory Diseases • SRSF7