1.
Therapeutic Options for Homozygous Familial Hypercholesterolemia: The Role of Lomitapide.
Giammanco, A, Cefalù, AB, Noto, D, Averna, MR
Current medicinal chemistry. 2020;(23):3773-3783
Abstract
BACKGROUND Lomitapide (Juxtapid® in US and Lojuxta® in Europe) is the first developed inhibitor of the Microsomal Triglyceride Transfer Protein (MTP) approved as a novel drug for the management of Homozygous Familial Hypercholesterolemia (HoFH). It acts by binding directly and selectively to MTP thus decreasing the assembly and secretion of the apo-B containing lipoproteins both in the liver and in the intestine. AIMS The present review aims at summarizing the recent knowledge on lomitapide in the management of HoFH. RESULTS The efficacy and safety of lomitapide have been evaluated in several trials and it has been shown a reduction of the plasma levels of Low-Density Lipoprotein Cholesterol (LDL-C) by an average of more than 50%. Although the most common side effects are gastrointestinal and liver events, lomitapide presents generally with a good tolerability and satisfactory patients compliance. Recently, in Europe, to evaluate the long-term safety and efficacy of lomitapide, the LOWER registry (ClinicalTrials.gov Identifier: NCT02135705) has been established in order to acquire informations on HoFH lomitapidetreated patients from "real life" clinical practice. Furthermore, the observation that lomitapide decreases triglyceride levels may be considered for patients affected by severe forms of hypertriglyceridemia who undergo recurrent episodes of pancreatitis and are poor responders to conventional treatment. CONCLUSION Lomitapide represents an innovative and efficacious drug for the treatment of HoFH. Longterm safety data, treatment of pediatric and pregnant HoFH patients and management of severe hypertriglyceridemia still require further investigations.
2.
Successful treatment of chronic hepatitis C virus infection with crushed glecaprevir/pibrentasvir administered via a percutaneous endoscopic gastrostomy tube: case report and review of the literature.
Tanaka, Y, Tateishi, R, Koike, K
Clinical journal of gastroenterology. 2019;(6):588-591
Abstract
Glecaprevir (GLE)/pibrentasvir (PIB) is a direct-acting antiviral regimen approved for patients infected with hepatitis C virus. No data are available on the safety and efficacy of this regimen when crushed and administered through a percutaneous endoscopic gastrostomy (PEG) tube. Here, we report a patient who successfully achieved a sustained viral response after treatment with GLE/PIB administered via a PEG tube. A 41-year-old female with chronic hepatitis C viral infection was referred to our department for treatment. She had a history of spina bifida and hydrocephalus, and she received a PEG tube for nutrition and medication due to an aftereffect of hydrocephalus. She received crushed GLE/PIB treatment through a PEG tube for 8 weeks and achieved a sustained viral response 12, without any treatment-related severe adverse events. This is the first documented case treated with GLE/PIB administered through a PEG tube. Based on this case report and a review of the literature, we discuss the safety and efficacy of direct-acting antiviral treatment via a PEG tube.
3.
Lomitapide and Mipomersen-Inhibiting Microsomal Triglyceride Transfer Protein (MTP) and apoB100 Synthesis.
Blom, DJ, Raal, FJ, Santos, RD, Marais, AD
Current atherosclerosis reports. 2019;(12):48
Abstract
PURPOSE OF REVIEW The goal of this review is to evaluate the role of inhibiting the synthesis of lipoproteins when there is no or little residual LDL-receptor function as in patients with homozygous familial hypercholesterolaemia. Lomitapide is administered orally once a day while mipomersen is given by subcutaneous injection once a week. Lomitapide inhibits microsomal triglyceride transfer protein while mipomersen is an antisense oligonucleotide directed against apoB100. RECENT FINDINGS The pivotal registration trials for lomitapide and mipomersen were published in 2013 and 2010, respectively. More recently published data from extension trials and cohort studies provides additional information on long-term safety and efficacy. The mean LDL cholesterol reduction was 50% with lomitapide in its single-arm open-label registration trial. Mipomersen reduced LDL cholesterol by approximately 25% in its double-blind, placebo-controlled registration study. Both lomitapide and mipomersen therapy are associated with variable increases in hepatic fat content. The long-term safety of increased hepatic fat content in patients receiving these therapies is uncertain and requires further study. Both drugs may cause elevated transaminase in some patients, but no cases of severe liver injury have been reported. Lomitapide may also cause gastrointestinal discomfort and diarrhoea, especially if patients consume high-fat meals and patients are advised to follow a low-fat diet supplemented with essential fatty acids and fat-soluble vitamins. Mipomersen may cause injection-site and influenza-like reactions. The effect of lomitapide and mipomersen on cardiovascular outcomes has not been studied, but circumstantial evidence suggests that the LDL cholesterol lowering achieved with these two agents may reduce cardiovascular event rates.
4.
Abemaciclib: The Newest CDK4/6 Inhibitor for the Treatment of Breast Cancer.
Palumbo, A, Lau, G, Saraceni, M
The Annals of pharmacotherapy. 2019;(2):178-185
Abstract
OBJECTIVE To review the pharmacology, efficacy, and safety of the cyclin-dependent kinase (CDK) inhibitor, abemaciclib, in the treatment of advanced or metastatic breast cancer (MBC). DATA SOURCES Relevant information was identified through a MEDLINE/PubMed (January 2000 to June 2018) literature search. The new drug application, prescribing information, and abstracts and posters from scientific meetings were also reviewed. STUDY SELECTION/DATA EXTRACTION The literature search was limited to human studies published in the English language. Phase 1, 2, and 3 studies evaluating the pharmacology, efficacy, or safety of abemaciclib for breast cancer were included. DATA SYNTHESIS Abemaciclib is an oral, potent, small molecule inhibitor of CDK4 and CDK6 activity, which blocks retinoblastoma tumor suppressor protein phosphorylation and thereby prevents progression through the cell cycle. Three major clinical trials, MONARCH 1, 2, and 3, established the efficacy and safety of abemaciclib for the treatment of hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or MBC. In these trials, response rates were promising, ranging from 19.7% to 59%, and median progression-free survival was significantly prolonged over the control arm in 2 of the trials. Common adverse effects included diarrhea, neutropenia, nausea, abdominal pain, infections, and fatigue. Relevance to Patient Care and Clinical Practice: Although no head-to-head studies have been completed between the CDK4/6 inhibitors, abemaciclib may be an attractive option because of its continuous dosing and ability to be used as monotherapy. CONCLUSIONS Abemaciclib is an effective and well-tolerated treatment for HR-positive, HER2-negative advanced or metastatic breast cancer.