Amgen cholesterol drug hits trial target

A new treatment for patients with extremely high cholesterol levels has hit its primary endpoint – but Amgen has held back from releasing the top line data.

A phase III trial of evolocumab found the drug met its primary endpoint of the percent reduction from baseline at week 12 in low-density lipoprotein cholesterol (LDL-C) in patients with homozygous familial hypercholesterolemia (HoFH). The condition is a rare and serious genetic disorder characterised by severely elevated LDL-C at an early age.

However Amgen would only say the percent reduction in LDL-C was "clinically meaningful and statistically significant", raising questions about just how convincing the results are.

The firm says details of the phase III trial, called TESLA, will be submitted to a future medical conference and for publication.

Amgen's drug is unlikely to win market share to treat the average patient with raised cholesterol levels, as this is dominated by the statin class, where atorvastatin (Pfizer's Lipitor) is now available as a cheap generic.

But in the most hard to treat cases, and in those patients who cannot tolerate statins, Amgen's drug could see significant uptake.

Evolocumab is a monoclonal antibody that is administered by subcutaneous injection once a month or once a fortnight.

The drug works by blocking PCSK9, a protein that keeps LDL levels elevated in the bloodstream. Evolocumab is not the only PCSK9 inhibitor, with rival molecules being developed by Pfizer and by a partnership between Sanofi and Regeneron. The partners released late last year promising phase III data showing their drug alirocumab worked well as a monotherapy – lowering LDL cholesterol three times more than Merck's Zetia (ezetimibe)

Analysts predict the best drugs in the class could achieve peak sales of $3-4 billion, and the rivals are now competing on who can produce the most convincing results and gain market approval first.

Huge trial programme

Amgen are undertaking a very extensive phase III trial programme, evaluating evolocumab in 20 clinical trials, with a combined planned enrollment of nearly 30,000 patients.

No fewer than five studies in the evolocumab phase III programme will provide long-term safety and efficacy data, including the FOURIER trial which will assess whether evolocumab in combination with statin therapy compared to placebo and statin therapy reduces recurrent cardiovascular events in approximately 22,500 patients with existing cardiovascular disease.

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Cholesterol lowering drugs: the race is on!