Pfizer looks likely to be third to market with its PCSK9 inhibitor bococizumab, but it seems determined to make the most of its chance. Amgen’s Repatha and Sanofi/Regeneron’s Praluent are approved but are still awaiting data from their cardiovascular outcomes studies which are important for label expansion and thus greater sales. Boco is expecting results from similar trials as early as next year (see tables below).
If these succeed, boco might not suffer too much for its late entry. Entry itself must come first, though, and this depends on two phase III studies of the drug which are due to report later this year – completing a set of six lipid-lowering trials, four of which have already come in positive.
Repatha on top
Since the launch of the two approved PCSK9 antibodies last year, Repatha seems to be coming out on top so far in a close fight (Amgen starts to gain upper hand in PCSK9 battle, February 3, 2016).
But this could all change with the upcoming cardiovascular outcomes data. Amgen expects results from its Fourier study in the second half of this year, while Sanofi/Regeneron’s CVOT trial, Odyssey Outcomes, has a primary completion date of December 2017.
The first CVOT study of boco, Spire-2, was fully enrolled in April, and Pfizer said it should conclude in the second half of 2017, putting it on a similar timeline to Praluent. If things go Pfizer’s way boco – already Pfizer’s biggest pipeline hope – could see an upgrade, bringing its sales forecast closer to its two approved rivals.
|Top-five PCSK9 inhibitors|
|Project||Company||Status||2022e sales ($m)|
|ALN-PCSsc||The Medicines Company||Phase II||233|
|LY3015014||Eli Lilly||Phase II||11|
Pfizer claims that Spire is the only PCSK9 inhibitor research programme assessing cardiovascular outcomes in a broad range of high-risk patients, including those with diabetes, chronic kidney disease and history of heart attack or stroke.
Fourier, meanwhile, is evaluating patients with cardiovascular disease and Odyssey Outcomes includes those who have recently experienced an acute coronary syndrome. Pfizer will hope that its broader pool of patients could give boco an edge.
|PCSK9 inhibitor cardiovascular outcomes studies|
|Project||Company||Study||No of patients||Trial ID||Primary completion|
|Praluent||Sanofi/Regeneron||Odyssey Outcomes||18,600||NCT01663402||Dec 2017|
Of course, boco first has to get the regulatory go-ahead. This is looking more likely after positive results from two more phase III trials: Spire-FH and Spire-HR, in familial hypercholesterolaemia patients and those at high risk of cardiovascular events respectively. This adds to the success already reported in the Spire SI and Spire-AI studies.
Next up will be Spire-LL and the biggest trial aimed at achieving approval, the 1,900-patient Spire-LDL. Both have primary completion dates of July 2016, according to Clinicaltrials.gov, and both have the primary endpoint of percent change from baseline in low-density lipoprotein cholesterol (LDL-C) at 12 weeks – the same endpoint as the just-reported Spire-HR and Spire-FH.
Back in the statin era meeting these kinds of endpoints used to be enough for broad approval but regulators – and payers – are increasingly demanding evidence that cholesterol-lowering drugs also reduce the incidence of cardiovascular deaths and other events.
Pfizer has been smart in getting its CVOT studies under way well in advance of approval. As the PCSK9 field gets increasingly crowded an advantage here will be invaluable.
|Study||Setting||Trial ID||Primary completion|
|Spire-FH||Heterozygous familial hypercholesterolaemia||NCT01968980||Reported|
|Spire-HR||Hyperlipidaemia or mixed dyslipidaemia at risk of cardiovascular events||NCT01968954||Reported|
|Spire-LDL||Hyperlipidaemia or mixed dyslipidaemia at risk of cardiovascular events||NCT01968967||Jul 2016|
|Spire-LL||Primary hyperlipidaemia or mixed dyslipidaemia at risk of cardiovascular events||NCT02100514||Jul 2016|