Chasing Novartis, Amgen ushers Lp(a) drug into phase 3

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Amgen has reported encouraging mid-stage results for its olpasiran candidate for reducing lipoprotein(a) – a risk factor for atherosclerotic cardiovascular disease – and now plans to move ahead swiftly with a phase 3 programme.

Final results of the OCEAN(a)-DOSE trial – published in the New England Journal of Medicine – showed that the small, interfering RNA (siRNA) drug reduced Lp(a) levels compared to placebo at all four doses tested, with doses above 75 mg given every 12 weeks, cutting levels by 95% or more after six months.

Amgen still needs to show that the reduction in Lp(a) is accompanied by lower rates of cardiovascular outcomes, and will endeavour to show that in its phase 3 programme which will start to enrol a target of 6,000 patients starting later this year.

The company reported top-line data from the study earlier this year, without sharing detailed results. It is playing catch-up with a rival Lp(a) targeting antisense drug from Novartis and development partner Akcea, called pelacarsen, which is already in a phase 3 trial called HORIZON with major cardiovascular events (MACE) as its primary endpoint.

Phase 2 results with once-weekly dosing of 20mg pelacarsen showed that 98% of patients achieved a reduction in Lp(a) levels that took them below the 50mg/dL threshold considered to be a risk, prompting Novartis to exercise a $150 million option on the drug in 2019.

Amgen's less frequent dosing could stand in its favour, but the sheer scale of the potential opportunity means that there could be plenty of room in the market for both drugs, if approved.

It is estimated that about 50% of atherosclerotic cardiovascular disease is not driven by LDL-cholesterol – the target of most lipid-lowering drugs, including statins and PCSK9 inhibitors like Amgen's own Repatha (evolocumab) – and that the majority of those cases are Lp(a) driven.

Diet and exercise – as well as current dugs – seem to have minimal influence on Lp(a) levels, along with currently available medicines. In OCEAN(a)-DOSE, most patients were already on other therapies, including statins, PCSK9 drugs, and cholesterol absorption inhibitor ezetimibe.

"Epidemiological research has shown us that Lp(a) is an independent risk factor and is primarily genetically determined," commented David Reese, Amgen's R&D head.

"It has been estimated that up to 20% of people worldwide are living with elevated levels, which are linked to a higher risk for heart disease, stroke, and the potential significant burden on patients with cardiovascular disease," he added.