Dive Brief:

• A new study expected to kick off in June will evaluate whether Amgen's cholesterol drug Repatha can cut the risk of cardiovascular events like strokes or heart attacks in patients who — while predisposed — haven't yet experienced such events.
• Amgen expects to enroll around 13,000 patients with coronary artery disease, peripheral arterial disease or other select factors that put them at high risk for cardiovascular events. The study was posted Wednesday on a federal clinical trial database and has a primary completion date scheduled for May 2024.
• In December 2017, Repatha gained U.S. approval as a treatment for preventing heart attack, stroke and coronary revascularization in adults with established cardiovascular disease. The drug is part of a new class of cholesterol-lowering therapies called PCSK9 inhibitors that, while effective, have not seen huge market success because of pushback from payers on their price tags. 

Dive Insight:

Amgen's new trial indicates the company isn't done in its efforts to broaden the market for Repatha (evolocumab), a drug that has yet to live up to its once loftier sales expectations.

The biotech estimates the on-label addressable patient population for Repatha currently sits at 11 million in the U.S. But should it gain approval in the secondary prevention setting for patients who haven't yet had a cardiovascular event, that number could grow by 4.5 million.

Consensus estimates put peak worldwide sales of Repatha at around $2.5 billion, according to investment bank Mizuho Securities.

Wall Street had high hopes for Repatha as well as Sanofi and Regeneron's Praluent (alirocumab) when the drugs came to market more than three years ago. Though initially pegged as soon-to-be blockbusters, sales from the PCSK9 drugs have mostly disappointed as their manufacturers struggled to secure payer coverage.

Last year, Repatha fetched $550 million while Praluent brought in $307 million.

Against those headwinds, Amgen, Sanofi and Regeneron have taken the unusual step of lowering the list prices on their products. Repatha's went from $14,523 to $5,850 in October, while Praluent's came down from $14,625 to $5,850 starting this month.​

So far, Repatha has outpaced its main rival, with Amgen's drug holding a nearly 70% share of total weekly PCSK9 prescriptions, according to data from Iqvia cited by Mizuho. 

A label expansion could help Repatha further solidify that leading position. Yet the new cardiovascular outcomes trial raises several questions.

For instance, Amgen is trying wrap up the study seven months before The Medicines Company completes a similarly structured Phase 3 study called ORION-4, which is testing inclisiran as a secondary prevention treatment for patients who have experienced a cardiovascular event. The issue: that investigation began in October 2018, eight months before Amgen's is slated to begin. 

That goal is ambitious, according to Mizuho's Salim Syed, who noted it's not guaranteed that enough patients in Amgen's study will experience a heart event to meet the company's timeline. 

Syed also theorized that Amgen's trial design implies the big biotech believes ORION-4 will readout positive, with inclisiran hitting on the primary endpoint of a 25% benefit — higher than 15% seen in the FOURIER trial of Repatha that led to its approval as a preventative therapy for adults with a history of cardiovascular disease.