• About
  • Masthead
  • License Content
  • Advertise
  • Submit Press Release
  • RSS/Email List
  • Write for us
  • Contact us
2 Minute Medicine
No Result
View All Result

No products in the cart.

SUBSCRIBE
  • Specialties
    • Cardiology
    • Chronic Disease
    • Dermatology
    • Emergency
    • Endocrinology
    • Gastroenterology
    • Imaging and Intervention
    • Infectious Disease
    • Nephrology
    • Neurology
    • Obstetrics
    • Oncology
    • Ophthalmology
    • Pediatrics
    • Preclinical
    • Psychiatry
    • Public Health
    • Pulmonology
    • Rheumatology
    • Surgery
  • The Scan
  • Wellness
  • Classics™
    • 2MM+ Online Access
    • Paperback and Ebook
  • Rewinds
  • Visual
  • Partners
    • License Content
    • Submit Press Release
    • Advertise with Us
  • AccountLog-in/out
    • Subscribe
    • Sign-in
    • My account
2 Minute Medicine
  • Specialties
    • Cardiology
    • Chronic Disease
    • Dermatology
    • Emergency
    • Endocrinology
    • Gastroenterology
    • Imaging and Intervention
    • Infectious Disease
    • Nephrology
    • Neurology
    • Obstetrics
    • Oncology
    • Ophthalmology
    • Pediatrics
    • Preclinical
    • Psychiatry
    • Public Health
    • Pulmonology
    • Rheumatology
    • Surgery
  • The Scan
  • Wellness
  • Classics™
    • 2MM+ Online Access
    • Paperback and Ebook
  • Rewinds
  • Visual
  • Partners
    • License Content
    • Submit Press Release
    • Advertise with Us
  • AccountLog-in/out
    • Subscribe
    • Sign-in
    • My account
SUBSCRIBE
2 Minute Medicine
Subscribe
Home All Specialties Cardiology

Lomitapide reduces LDL-C by 38% in patients with devastating homozygous familial hypercholesterolemia

bys25qthea
November 6, 2012
in Cardiology, Chronic Disease
Reading Time: 4 mins read
0
Share on FacebookShare on Twitter

Image: PD/Cholesterol

Key study points:

1. Lomitapide reduces plasma LDL-C by 50% (at 26 weeks) and 38% (at 78 weeks) in patients with homozygous familial hypercholesterolemia.

2. Lomitapide increases hepatic fat content by 8.3% (at 78 weeks).

Primer: Familial hypercholesterolemia (FH) is a genetic disease with clinically detectable elevated plasma low-density lipoprotein cholesterol (LDL-C) levels from the time of birth and results in premature atherosclerosis. The disease is caused by genetic mutations in genes responsible for clearance of the LDL-particle from the blood via the liver. In the most severe and fatal form, homozygous familial hypercholesterolemia (HoFH), the causative mutations reside in both alleles of the LDL-receptor gene (LDLR).

HoFH often presents with the classic findings of xanthelasma palpebrarum, tendon xanthomata, and arcus senilis. Further, the aggressive atherosclerosis associated with HoFH causes significant coronary artery disease, typically requiring numerous surgical interventions including coronary artery bypass grafting (CABG) and angioplasty, and often results in death prior to age 30. Indeed, this grave prognosis highlights the great need for effective LDL-lowering therapies within the HoFH patient population. The current standard of care is comprised of LDL apheresis (for acute LDL reduction only) and pharmacological interventions, including lipid-lowering statins in combination with ezetimibe. However, the efficacy of these pharmacologics are diminished by the dysfunctional LDL-receptors present in HoFH patients, rendering cells unable to remove circulating LDL-particles from the blood.

Lomitapide is a small-molecule inhibitor of the enzymatic microsomal triglyceride transfer protein (MTP) that is vital to the formation of LDL precursor particles. Thus, pharmacologic inhibition of MTP decreases formation of chylomicrons and very-low-density lipoprotein (VLDL) particles resulting in net LDL-particle reduction. Lomitapide does not depend on functional LDL-receptors, unlike statins, where inhibition of HMG-CoA reductase results in the upregulation of hepatic LDL-receptors and increased clearance of circulating plasma LDL-particles. Thus, lomitapide is a promising treatment strategy for HoFH.

RELATED REPORTS

Dual antiplatelet therapy discontinued 9 months after percutaneous coronary intervention associated with improved morbidity and mortality

Concordance of diagnosis of autism spectrum disorder made by pediatricians vs multidisciplinary specialist teams

Cystatin C-based equation without race or sex improves accuracy of GFR estimation

Background reading:

1. An MTP Inhibitor That Normalizes Atherogenic Lipoprotein Levels in WHHL Rabbits [Science]

2. Inhibition of Microsomal Triglyceride Transfer Protein in Familial Hypercholesterolemia [NEJM]

3. Primary disorders of LDL cholesterol metabolism [UpToDate]

This [phase III] trial: This Phase III, non-randomized, unmasked, single arm study evaluated the efficacy and safety of the oral MTP inhibitor, Lomitapide, in patients with homozygous familial hypercholesterolemia (HoFH). 23 men and women at 11 clinical centers with genetically confirmed cases of HoFH entered the trial. A regimen of lipid-lowering medications (Lopitapide + participants current lipid-reduction therapies), apheresis, supplementations of vitamin E and essential fatty acids, and a low-fat diet was initiated and patients were followed for a total of 78 weeks (26 week second phase for drug efficacy, 52 week third phase for safety). Percent change in LDL-C from baseline to maximum dosage Lomitapide (at week 26 of treatment) was noted for each participant. Percent hepatic fat content was also evaluated at baseline and at 6-month intervals due to previous clinical trial findings of increased hepatic fat content with Lomitapide use.

At 26 weeks of treatment, LDL-C decreased 50% (range -62% to -39%; p-value <0.0001). At 78 weeks, LDL-C levels were decreased by 38% (range -52% to -24%; p-value= 0.001). At 26 weeks, mean hepatic fat content increased to 8.6% (range 0-33.6%) from 1.0% (range 0-5.0%) at baseline. Hepatic fat content stabilized at 8.3% (0-19.0%) at 78 weeks. Elevations of ALT and/or AST greater than three times the upper-limit-of-normal occurred in 10 patients during the study. 80% of patients experienced gastrointestinal side effects.

In sum: Significant unmet medical needs exist for the HoFH patient population. This study demonstrated the safety and efficacy of oral Lomitapide for significant reduction of LDL-C and total cholesterol in adult patients with HoFH. Lomitapide may improve overall patient outcomes and survival, and may even reduce severity of cardiovascular disease within this population. However, this study faces several significant limitations. First, the design of the study lacks a control group, thus it is difficult to truly differentiate improvements due to treatment with Lomitapide versus improvements due to the other aspects of the trial regimen (therapy standardization, diet changes, vitamin supplementation, etc.). Further, while the authors followed the study participants for a total of 78 weeks, long-term studies are needed to ensure increased hepatic fat content does not progress to hepatic fibrosis or cirrhosis. Finally, additional studies are needed to address safety and efficacy in children to extend this pharmacologic agent to a younger but equally high-risk patient population.

Click to read the study in [The Lancet]

Click to read an accompanying editorial in [The Lancet]

By [ME] and [MM]

© 2012 2minutemedicine.com. All rights reserved. No works may be reproduced without written consent from 2minutemedicine.com. DISCLAIMER: Posts are not medical advice and are not intended as such. Please see a healthcare professional if you seek medical advice.

Previous Post

Neonatal care not associated with early developmental delays in children born late preterm

Next Post

Omega-3 Fatty Acids not effective in prevention of post-operative atrial fibrillation [OPERA trial] {In the Media}

RelatedReports

Drug-coated balloons are noninferior to drug-eluting stents for treatment of small vessel coronary artery disease
Cardiology

Dual antiplatelet therapy discontinued 9 months after percutaneous coronary intervention associated with improved morbidity and mortality

February 4, 2023
Quick Take: Association of Prenatal Exposure to Air Pollution with Autism Spectrum Disorder
Neurology

Concordance of diagnosis of autism spectrum disorder made by pediatricians vs multidisciplinary specialist teams

February 3, 2023
Intravenous contrast may not increase risk of acute kidney injury
Chronic Disease

Cystatin C-based equation without race or sex improves accuracy of GFR estimation

February 3, 2023
#VisualAbstract: Aldosterone synthase inhibition reduced systolic blood pressure in patients with treatment-resistant hypertension
StudyGraphics

#VisualAbstract: Aldosterone synthase inhibition reduced systolic blood pressure in patients with treatment-resistant hypertension

February 3, 2023
Next Post

Omega-3 Fatty Acids not effective in prevention of post-operative atrial fibrillation [OPERA trial] {In the Media}

No difference in bowel obstruction rates following closure of diverting loop ileostomy via either handsewn or stapler techniques: the HASTA trial

The ALTITUDE trial: Aliskiren increases the risk of adverse events and stroke without any cardiovascular or renal improvements in patients with Type 2 Diabetes

License Our Award-Winning Physician-Written Medical News and Visual Abstracts

2 Minute Medicine is the leading authoritative medical news licensing service, and the only with reports written by practicing doctors.

LICENSE CONTENT

2MM+ Premium Access

No ads & unlimited access to all current reports, over 9000 searchable archived reports, visual abstracts, Weekly Rewinds, and the online edition of The Classics Series™ textbook.

Subscription Options
2 Minute Medicine

2 Minute Medicine® is an award winning, physician-run, expert medical media company. Our content is curated, written and edited by practicing health professionals who have clinical and scientific expertise in their field of reporting. Our editorial management team is comprised of highly-trained MD physicians. Join numerous brands, companies, and hospitals who trust our licensed content.

Recent Reports

  • Dual antiplatelet therapy discontinued 9 months after percutaneous coronary intervention associated with improved morbidity and mortality
  • Concordance of diagnosis of autism spectrum disorder made by pediatricians vs multidisciplinary specialist teams
  • Cystatin C-based equation without race or sex improves accuracy of GFR estimation
License Content
Terms of Use | Disclaimer
Cookie Policy
Privacy Statement (EU)
Disclaimer

© 2021 2 Minute Medicine, Inc. - Physician-written medical news.

  • Specialties
    • Cardiology
    • Chronic Disease
    • Dermatology
    • Emergency
    • Endocrinology
    • Gastroenterology
    • Imaging and Intervention
    • Infectious Disease
    • Nephrology
    • Neurology
    • Obstetrics
    • Oncology
    • Ophthalmology
    • Pediatrics
    • Preclinical
    • Psychiatry
    • Public Health
    • Pulmonology
    • Rheumatology
    • Surgery
  • The Scan
  • Wellness
  • Classics™
    • 2MM+ Online Access
    • Paperback and Ebook
  • Rewinds
  • Visual
  • Partners
    • License Content
    • Submit Press Release
    • Advertise with Us
  • Account
    • Subscribe
    • Sign-in
    • My account

© 2021 2 Minute Medicine, Inc. - Physician-written medical news.

Want more physician-written
medical news?

Join over 10 million yearly readers and numerous companies. For healthcare professionals
and the public.

Subscribe for free today!

Subscription options