Amgen Announces Positive Results At ACC.20/WCC From Phase 3B Study Of Repatha® (Evolocumab) In People Living With HIV Who Have High LDL-Cholesterol
"Certain antiretroviral treatments for HIV can increase LDL-C and change the lipid makeup of people living with HIV. This study increases our overall evidence base for Repatha, but also provides us with a better understanding of cholesterol management for this under-represented patient population," said
Results from the double-blind 24-week study show that in people living with HIV (PLHIV) with hypercholesterolemia or mixed dyslipidemia, monthly treatment with Repatha reduced LDL-C by 56.9% from baseline compared to placebo, meeting its primary endpoint.1 Patients treated with Repatha also demonstrated improved secondary outcomes versus placebo with 71.9% of patients achieving an LDL-C reduction of more than or equal to 50% from baseline and 65.4% of patients achieving an LDL-C of less than 70 mg/dL.1 No new safety concerns were identified in the BEIJERINCK trial.1 The subject incidence of treatment-emergent adverse events was comparable among both groups.1
"Professional guidelines, including most recently those from the
Approximately 38 million individuals live with HIV worldwide, with 1.1 million in
The Phase 3b BEIJERINCK study is part of
About BEIJERINCK Study Design
EvolocumaB Effect on LDL-C LowerIng in SubJEcts with Human Immunodeficiency ViRus and INcreased Cardiovascular RisK (BEIJERINCK) is a double-blind, randomized, placebo-controlled study designed to evaluate the efficacy and safety of 420 mg once-monthly treatment with evolocumab in HIV+ patients with hyperlipidemia or mixed dyslipidemia over 24 weeks. The study enrolled 467 adults with known HIV infection who have received stable HIV therapy for six months or more prior to randomization and have also been treated with maximally tolerated lipid-lowering therapy for four weeks or longer prior to randomization. Both background therapies were not expected to change during the duration of study participation. Statin-intolerant patients were also eligible for the study. Evolocumab-treated patients who completed the 24-week double-blind treatment period were enrolled in an open-label period through the end of the study at week 52.
About Repatha® (evolocumab)
Repatha is a human monoclonal antibody that inhibits proprotein convertase subtilisin/kexin type 9 (PCSK9). Repatha binds to PCSK9 and inhibits circulating PCSK9 from binding to the low-density lipoprotein (LDL) receptor (LDLR), preventing PCSK9-mediated LDLR degradation and permitting LDLR to recycle back to the liver cell surface. By inhibiting the binding of PCSK9 to LDLR, Repatha increases the number of LDLRs available to clear LDL from the blood, thereby lowering LDL-C levels.7
Repatha is approved in more than 70 countries, including the U.S., Japan, Canada and in all 28 countries that are members of the European Union. Applications in other countries are pending.
Repatha is a PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitor antibody indicated:
- to reduce the risk of myocardial infarction, stroke, and coronary revascularization in adults with established cardiovascular disease.
- as an adjunct to diet, alone or in combination with other lipid-lowering therapies (e.g., statins, ezetimibe), for treatment of adults with primary hyperlipidemia (including heterozygous familial hypercholesterolemia [HeFH]) to reduce low-density lipoprotein cholesterol (LDL-C).
- as an adjunct to diet and other LDL-lowering therapies (e.g., statins, ezetimibe, LDL apheresis) in patients with homozygous familial hypercholesterolemia (HoFH) who require additional lowering of LDL-C.
The safety and effectiveness of Repatha have not been established in pediatric patients with HoFH who are younger than 13 years old or in pediatric patients with primary hyperlipidemia or HeFH.
Contraindication: Repatha is contraindicated in patients with a history of a serious hypersensitivity reaction to Repatha. Serious hypersensitivity reactions including angioedema have occurred in patients treated with Repatha.
Allergic reactions: Hypersensitivity reactions (e.g. angioedema, rash, urticaria) have been reported in patients treated with Repatha, including some that led to discontinuation of therapy. If signs or symptoms of serious allergic reactions occur, discontinue treatment with Repatha, treat according to the standard of care, and monitor until signs and symptoms resolve.
Adverse reactions: The most common adverse reactions (>5% of patients treated with Repatha and occurring more frequently than placebo) were: nasopharyngitis, upper respiratory tract infection, influenza, back pain, and injection site reactions.
From a pool of the 52-week trial and seven 12-week trials: Local injection site reactions occurred in 3.2% and 3.0% of Repatha-treated and placebo-treated patients, respectively. The most common injection site reactions were erythema, pain, and bruising.
Allergic reactions occurred in 5.1% and 4.7% of Repatha-treated and placebo-treated patients, respectively. The most common allergic reactions were rash (1.0% versus 0.5% for Repatha and placebo, respectively), eczema (0.4% versus 0.2%), erythema (0.4% versus 0.2%), and urticaria (0.4% versus 0.1%).
The most common adverse reactions in the Cardiovascular Outcomes Trial (>5% of patients treated with Repatha and occurring more frequently than placebo) were: diabetes mellitus (8.8% Repatha, 8.2% placebo), nasopharyngitis (7.8% Repatha, 7.4% placebo), and upper respiratory tract infection (5.1% Repatha, 4.8% placebo).
Among the 16,676 patients without diabetes mellitus at baseline, the incidence of new-onset diabetes mellitus during the trial was 8.1% in patients assigned to Repatha compared with 7.7% in those assigned to placebo.
Homozygous Familial Hypercholesterolemia (HoFH): The adverse reactions that occurred in at least two patients treated with Repatha and more frequently than placebo were: upper respiratory tract infection, influenza, gastroenteritis, and nasopharyngitis.
Immunogenicity: Repatha is a human monoclonal antibody. As with all therapeutic proteins, there is a potential for immunogenicity with Repatha.
About Amgen in the Cardiovascular Therapeutic Area
Building on more than three decades of experience in developing biotechnology medicines for patients with serious illnesses, Amgen is dedicated to addressing important scientific questions to advance care and improve the lives of patients with cardiovascular disease, the leading cause of morbidity and mortality worldwide.
This news release contains forward-looking statements that are based on the current expectations and beliefs of
No forward-looking statement can be guaranteed and actual results may differ materially from those we project. Discovery or identification of new product candidates or development of new indications for existing products cannot be guaranteed and movement from concept to product is uncertain; consequently, there can be no guarantee that any particular product candidate or development of a new indication for an existing product will be successful and become a commercial product. Further, preclinical results do not guarantee safe and effective performance of product candidates in humans. The complexity of the human body cannot be perfectly, or sometimes, even adequately modeled by computer or cell culture systems or animal models. The length of time that it takes for us to complete clinical trials and obtain regulatory approval for product marketing has in the past varied and we expect similar variability in the future. Even when clinical trials are successful, regulatory authorities may question the sufficiency for approval of the trial endpoints we have selected. We develop product candidates internally and through licensing collaborations, partnerships and joint ventures. Product candidates that are derived from relationships may be subject to disputes between the parties or may prove to be not as effective or as safe as we may have believed at the time of entering into such relationship. Also, we or others could identify safety, side effects or manufacturing problems with our products, including our devices, after they are on the market.
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The scientific information discussed in this news release relating to any new indications for our products is preliminary and investigative and is not part of the labeling approved by the
- Bocarra F., et al. Evolocumab Use in Patients With Human Immunodeficiency Virus and Dyslipidemia: Primary Results of a Double-Blind, Placebo-Controlled Study (BEIJERINCK). To be presented at ACC Scientific Sessions, Abstract Number 913-08 (2020).
World Health Organization. HIV/AIDS. Available at: https://www.who.int/gho/hiv/en/. Accessed February 2020. Centers for Disease Control and Prevention. HIV Surveillance Report, 2018 (Preliminary); vol. 30. Available at: http://www.cdc.gov/hiv/library/reports/hiv-surveillance.html. Accessed February 2020. Centers for Disease Control and Prevention. Estimated HIV incidence and prevalence in the United States, 2010–2016. HIV Surveillance Supplemental Report 2019;24(No. 1). Available at: http://www.cdc.gov/hiv/library/reports/hiv-surveillance.html. Accessed February 2020.
- Shah AS., et al. Global Burden of Atherosclerotic Cardiovascular Disease in People Living With HIV. Circulation. 2018;138:1100–1112.
American Heart Association. People living with HIV face premature heart disease and barriers to care. Available at: https://newsroom.heart.org/news/people-living-with-hiv-face-premature-heart-disease-and-barriers-to-care. Accessed February 2020.
- Repatha Prescribing Information;
Amgen, Thousand Oaks, CA, 2018.
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