Customize Consent Preferences

We use cookies to help you navigate efficiently and perform certain functions. You will find detailed information about all cookies under each consent category below.

The cookies that are categorized as "Necessary" are stored on your browser as they are essential for enabling the basic functionalities of the site. ... 

Always Active

Necessary cookies are required to enable the basic features of this site, such as providing secure log-in or adjusting your consent preferences. These cookies do not store any personally identifiable data.

No cookies to display.

Functional cookies help perform certain functionalities like sharing the content of the website on social media platforms, collecting feedback, and other third-party features.

No cookies to display.

Analytical cookies are used to understand how visitors interact with the website. These cookies help provide information on metrics such as the number of visitors, bounce rate, traffic source, etc.

No cookies to display.

Performance cookies are used to understand and analyze the key performance indexes of the website which helps in delivering a better user experience for the visitors.

No cookies to display.

Advertisement cookies are used to provide visitors with customized advertisements based on the pages you visited previously and to analyze the effectiveness of the ad campaigns.

No cookies to display.


Home > Cardiology > AHA 2021 > CVD Risk Reduction > Novel oral PCSK9 inhibitor shows promising results for hypercholesterolaemia

Novel oral PCSK9 inhibitor shows promising results for hypercholesterolaemia

Presented by
Dr Douglas Johns
Conference
AHA 2021
    MK-0616, an oral PCSK9 inhibitor in development, was efficacious in lowering LDL cholesterol in patients with hypercholesterolaemia treated with statins and showed a favourable safety profile across two phase 1 trials. An oral PCSK9 inhibitor could help to overcome treatment barriers, providing cardiovascular risk reductions for patients with hypercholesterolaemia in an earlier phase.

    Dr Douglas Johns (Merck & Co., NJ, USA) mentioned that many patients with hypercholesterolaemia do not reach their LDL cholesterol treatment goals [1]. Although injectable PCSK9 inhibitors demonstrated LDL cholesterol reductions of 50–60%, these therapies are often administered as a last resort only. An oral PCSK9 inhibitor could remove the barriers associated with injectable treatments.

    A first randomised, double-blind, placebo-controlled, in-human trial assessed the safety and tolerability of single doses of MK-0616 ranging from 10 mg to 300 mg in 60 male participants (aged 18–50 years). MK-0616 was generally safe and well tolerated in this population. No serious adverse events (AEs) were reported and only 1 treatment-related discontinuation was observed, a case of maculopapular rash. Drug-related AEs were mostly abdominal discomfort, diarrhoea, dyspepsia, and headache. Free PCSK9 was reduced by more than 80%, regardless of the administered dose of MK-0616. This effect lasted for approximately 24 hours. Free PCSK9 levels returned to baseline levels in 96 hours. In addition, the authors observed that a permeation enhancer (i.e. sodium caprate) improved the absorption of MK-0616 and noted a negative pre-dose food effect.

    A second double-blind, placebo-controlled, phase 1 trial evaluated the LDL-cholesterol lowering capacities of MK-0616 in 40 men and women (aged 18–65 years) treated with statin therapy. Patients were randomised 3:1 to 1 of 3 dosing regimens of MK-0616 or placebo (see Figure). The 14-day result displayed no serious AEs, deaths, or discontinuations. Treatment-related AEs were similar to the reported AEs in the first trial, demonstrating a favourable safety profile of the agent. LDL cholesterol was reduced by a maximum of 65% in all experimental conditions, except for the pre-dose food condition (see Figure). This result suggests that low-dose MK-0616 plus low-dose sodium caprate can achieve a major reduction in LDL cholesterol. Larger clinical trials need to confirm the safety and efficacy of MK-0616 in a diverse population.

    Figure: MK-0616 dosing and LDL-cholesterol change from baseline [1]



    LDL-C, low-density lipoprotein cholesterol; PBO, placebo.

     


      1. Johns DG, et al. The Clinical Safety, Pharmacokinetics, and LDL-Cholesterol Lowering Efficacy of MK-0616, an Oral PCSK9 Inhibitor. LBS06, AHA Scientific Sessions 2021, 13–15 November.

     

    Copyright ©2021 Medicom Medical Publishers



    Posted on