Amgen starts to gain upper hand in PCSK9 battle

The introduction of the PCSK9 antibodies Repatha and Praluent from Amgen and Sanofi/Regeneron last year was notable for the unusual circumstances where two potential blockbusters with an identical mechanism found themselves competing head-to-head almost from day one.

While sales figures for the products have yet to emerge, recent prescription data suggest that Repatha is gaining an early lead over Praluent. And this is starting to be reflected in the sellside's 2020 sales forecasts for the two drugs, which EvaluatePharma data show are starting to diverge (see graph below).

Naturally this head-to-head battle focuses interest on the competitive dynamics in this new market segment, which is estimated to be worth $5bn-plus – especially as payers, for once, expect to be in a position to play off one company against the other to extract sizeable price discounts.

Caution should of course be exercised when interpreting prescription trends at an early launch stage – and these could change dramatically when cardiovascular outcomes data become available. Furthermore, given the high cost of these drugs relative to generic statins – both have a gross price over $14,000 per year – US payers have imposed strict utilisation management criteria.

While these criteria are designed to ensure that prescriptions are reimbursed only when written in line with the label – both products have similar indications, though Repatha alone can also treat homozygous familial hypercholesterolaemia – they also strengthen the payer’s hand.

Major outcomes studies are under way for both products, and should report later this year. Amgen expects data from its large event-driven Fourier study as well as its Glagov trial, which measures plaque regression by intravascular ultrasound, to become available in the second half.

Meanwhile, Sanofi and Regeneron expect results from their Odyssey Outcomes study at the end of the year. The two major outcomes trials recruited slightly different populations, so it is not clear whether they can be compared.

Fourier enrolled patients at elevated risk of a cardiovascular event by virtue of lipid parameters alone, while Odyssey Outcomes enrolled patients who had recently experienced an acute coronary event. Both have the same primary endpoint, however: time to CV death, non-fatal myocardial infarction, hospitalisation for unstable angina, non-fatal stroke, or unstable angina requiring coronary revascularisation.

The key ongoing phase III trials in the table below exclude several open-label extensions, safety studies and smaller phase III trials in Asian or paediatric populations. 

Study/patient type Design No. of patients Name Trial ID Primary completion
CVOT in subjects with elevated risk Statin +/- Repatha 27,564 Fourier NCT01764633 H2 2016
Plaque regression measured by IVUS, hypercholersterolaemia Statin/ezetimibe +/- Repatha 970 Glagov NCT01813422 July 2016
Statin intolerant, hyperlipidaemia Repatha vs Ezetimibe 519 - NCT01984424 November 2015
Cognitive health, dyslipidaemia Statin +/- Repatha 1,972 Ebbinghaus NCT02207634 October 2017
CVOT after an acute coronary syndrome Praluent vs placebo 18,600 Odyssey Outcomes NCT01663402 December 2017
High CV risk + severe hypercholesterolemia, inadequately controlled with conventional LMT Praluent (no control) 1,100 - NCT02476006 January 2018
Insulin-using diabetics with hypercholesterolaemia inadequately controlled with max-tol LMT LMT +/- Praluent 500 Odyssey DM-Insulin NCT02585778 February 2017

Another potenital entrant in the PCSK9 class is Pfizer's bococizumab, and that company has just reported a positive result in the first of its six phase III trials with the molecule. The Spire-SI study evaluated LDL-lowering in 184 patients who were intolerant of statins. The other studies are expected to complete throughout 2016.

IP problem

A further issue for Regeneron is a looming US patent infringement case that has been brought by Amgen and is scheduled to start on March 7, involving a seven-day jury trial with a permanent injunction hearing on March 23.

A US broker, Chardan Capital, has conducted an examination of the case with outside IP experts and concludes that Praluent infringes Amgen’s patents. As a result, it expects thatRegeneron, which holds the US rights, will have to negotiate a licence ahead of the trial, to avoid finding itself a worse situation if it were to lose the case. Chardan reckons that Regeneron could have to pay double-digit royalties to Amgen, even under this scanario.  

If this does occur it would obviously affect the profitability of the product and might in turn make the marketing investment harder to justify. But for the time being it is the outcomes data that most observers are looking towards to determine which product could end up strongest in the class.

To contact the writer of this story email Robin Davison at or follow @RobinDavison2 on Twitter

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