Amarin can be forgiven for saying “I told you so”. The company has unveiled unexpectedly positive results from Reduce-It, the make-or-break cardiovascular outcomes study of its fish oil product, Vascepa. Executives will not be alone in celebrating the outcome, five years in the making: investors who took a punt have been rewarded with a huge 250% leap in the company’s share price this morning.
The topline result is surely beyond Amarin’s wildest dreams: Vascepa reduced a patient’s relative risk of a major cardiovascular event by 25%, as compared with placebo. If this figure stands up to scrutiny it could shift the cardiology world’s opinion of certain fish oils – and leave Amarin with a very big product indeed.
The importance of this result can be illustrated by a look at other notable cardiovascular outcomes studies conducted with agents given on top of statins, as Vascepa was in Reduce-It. These trials enrolled different patient populations with different risk profiles so this is far from an apples-to-apples comparison, but it does highlight just how notable Amarin’s achievement is.
|Adding to statins? Notable outcome studies|
|Study||Drug/combination||Population||% reduction in risk of MACE||Trial ID|
|Reduce-IT||Vascepa (EPA plus statin)||High-risk patients with mixed dyslipidemia||25%||NCT01492361|
|Fourier||Repatha (PCSK9 plus statin)||High-risk patients with CV disease||15%||NCT01764633|
|Odyssey Outcomes||Praluent (PCSK9 plus statin)||High-risk ACS patients||15%||NCT01663402|
|Improve-IT||Vytorin (simvastatin plus ezetimibe)||High-risk ACS patients||6.4%||NCT00202878|
|Notes: CAD=coronary arterial disease. Source: company press releases, JAMA Cardiology.|
Only last month the failure of the Ascend trial of a rival fish oil product seemed to solidify the reputation of these pills as weakly efficacious at best. Amarin has long argued that Vascepa is better and different, and could have just proved itself correct (ESC 2018 – Amarin brushes off fish oil concerns, August 29, 2018).
Vascepa is a pure form of eicosapentaenoic acid (EPA) and does not contain docosahexanoic acid (DHA); marine-derived omega-3 products typically include both of these molecules. An important distinction, according to Amarin, is that DHA can cause LDL or “bad” cholesterol levels to rise, something that EPA does not do.
Full results of Reduce-It are due at the American Heart Association’s annual meeting in November, and physicians will be interested to see Vascepa’s impact on lipid profiles and other cardiovascular markers. On a call today Amarin stressed that Vascepa improved several components of a patient’s cardiovascular profile, not just triglyceride levels.
Details on secondary endpoints also remain hugely important to assess the real impact of this study. On the primary endpoint the outcome appears unequivocal: having been powered to show a 15% relative risk reduction, the study hit 25% with a p value of <0.001. Safety and tolerability were consistent with what is already known about the product.
The $2bn jump in Amarin’s market cap illustrates just how valuable investors believe this finding could be. Excitement is also high because the impact could be felt pretty quickly on sales: Vascepa is already on the market to treat severe hypertriglyceridaemia, at a fraction of the price of products like the PCSK9s.
Describing the future strategy for Vascepa as a “volume play not a pricing play”, chief executive John Thero said today that Amarin saw the product as more analogous to statins than “niche but important” products like the PCSK9s.
This would certainly mean a huge new patient population: there are more patients with elevated triglycerides than elevated LDL cholesterol, Mr Thero said. Questions on this afternoon’s conference call centred on the company’s ability to meet a sudden jump in demand, signalling that the financial community was convinced for now, and blockbuster sales forecasts have already emerged from the sellside.
One large cardiology player that will be looking on with interest is Astrazeneca, which has a rival fish product called Epanova that won FDA approval to treat severe hypertriglyceridaemia back in 2014. This has yet to be launched; the company has been focused on manufacturing enough product for an ongoing cardiovascular outcomes study called Strength, a spokesperson told Vantage today.
In reality, Astra has probably gauged that a launch without a cardiovascular claim makes no commercial sense. Strength has enrolled patients with similar risk factors to Reduce-It but is a much larger endeavour, with 13,086 patients to Reduce-It’s 8,179. Results are unlikely to emerge before 2020.
Like Lovaza, the subject of the failed Ascend trial, Epanova is a mixed fish oil product, although the two contain different amounts of EPA and DHA. Whether this is important could finally be answered by the Strength trial, though the fact that Astra felt the need to run such a huge study suggests that it does not expect to see a startling benefit. Like Reduce-It, Strength is testing a 4mg dose of fish oil, versus 1mg in the failed Ascend trial.
Of course, by the time Strength reads out none of this might matter to Amarin – assuming the full Reduce-It data leave little room for doubt. No product with a proven cardiovascular benefit is in the hands of a small company, another fact that will not have escaped investors’ notice this morning.
|Fish oil pharmacology|
|Per 1g capsule||EPA||DPA|
|Source: A Comparative Overview of Prescription Omega-3 Fatty Acid Products; P T. 2015 Dec; 40(12): 826-836, 857.|