REPATHA

What it is

Repatha is a solution for injection containing evolocumab . Repatha is available as a sterile, preservative-free solution containing 140 mg/mL evolocumab in a pre-filled syringe or pre-filled pen, or a 420 mg/3.5 mL solution delivering 120 mg/mL evolocumab in a pre-filled cartridge co-packaged with an automated mini-doser . Repatha binds selectively and with high affinity to PCSK9 and inhibits circulating PCSK9 from binding to the low-density lipoprotein receptor on the liver cell surface, thus preventing PCSK9-mediated LDLR degradation . Increasing liver LDLR levels results in associated reductions in serum low density lipoprotein-cholesterol .

Approved indications

— Reduction of the risk of cardiovascular events (myocardial infarction, stroke and coronary revascularisation) in adults with established cardiovascular disease in combination with an optimally dosed statin and/or other lipid-lowering therapies . — Reduction of low-density lipoprotein cholesterol in adults with primary hypercholesterolaemia (including heterozygous familial hypercholesterolaemia and non-familial hypercholesterolaemia) in combination with a statin or statin with other lipid lowering therapies, or alone or in combination with other lipid-lowering therapies in patients who are statin-intolerant . — Treatment of adults and adolescents aged 12 years and over with homozygous familial hypercholesterolaemia in combination with other lipid lowering therapies .

Dosing overview

No dose adjustment is necessary in patients with renal impairment . No dose adjustment is necessary in patients with mild to moderate hepatic impairment . No dose adjustment is necessary in elderly patients aged 65 years or older .

Key safety warnings

Hypersensitivity reactions (including rash and 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 . In clinical studies, 48 patients (0.3%) out of 17,992 patients treated with at least one dose of Repatha tested positive for anti-evolocumab binding antibodies, but none tested positive for neutralising antibodies . The presence of anti-evolocumab binding antibodies did not impact the pharmacokinetic profile, clinical response, or safety of evolocumab . Common adverse reactions include nausea, injection site reactions, influenza, nasopharyngitis, upper respiratory tract infection, arthralgia, back pain, and rash . Uncommon adverse reactions include urticaria .

Contraindications

Repatha is contraindicated in patients with known hypersensitivity to evolocumab or any of the excipients found in Repatha .

PBS listing

Repatha 140 mg in 1 mL single use pre-filled pen is listed on the PBS with a streamlined restriction at an ex-manufacturer price of A$190.00 .

Regulatory history

Repatha was first registered on the ARTG on 9 December 2015 in two presentations: 140 mg/mL injection solution syringe within a pen injector, and 140 mg/mL injection solution syringe; a 420 mg/3.5 mL injection solution automated mini-doser was added on 3 December 2020 . In March 2016, the PBAC recommended Authority Required listing for homozygous familial hypercholesterolaemia . In November 2017 and March 2018, the PBAC recommended amendments to expand eligibility to include patients with heterozygous familial hypercholesterolaemia who have not achieved adequate control with maximally tolerated statin therapy and ezetimibe . In November 2019, the PBAC recommended Authority Required listing for non-familial hypercholesterolaemia and extension for familial hypercholesterolaemia, noting moderate unmet clinical need and acceptable cost-effectiveness at the proposed price . In July 2022, the PBAC recommended listing for patients with LDL-C levels between 1.8 and 2.6 mmol/L despite optimised treatment with statins and ezetimibe . In March 2024, the PBAC recommended changes to the restriction level and reduction of minimum treatment duration .