Merck's cardiovascular future takes shape as sotatercept overachieves, PCSK9 inhibitor passes phase 2

For years, Merck & Co.’s most consequential clinical updates have often concerned Keytruda, the goldmine cancer treatment that’s redefined success for the company. But a new crop of cardiovascular readouts is continuing to build hope of fresh revenue streams to replace its oncology blockbuster.

Entering the last day of the American College of Cardiology's annual conference, the Big Pharma is trotting out new phase 2 data of its anti-PCSK9 drug, finding that it reduced particular kinds of cholesterol by up to 61% compared to placebo.

Meanwhile, expanded phase 3 data of sotatercept, added onto background therapy, has exceeded the expectations of Chief Medical Officer Eliav Barr, M.D. “It just hits the right receptor,” he said in an interview with Fierce Biotech. 

Sotatercept was the prized jewel in the company’s $11.5 billion purchase of Acceleron Pharma in 2021. The cardio med aimed at treating pulmonary arterial hypertension improved patients’ six-minute walk distance by more than 40 meters after 24 weeks compared to placebo, hitting the primary endpoint of the 323-patient trial.

The therapy also reduced the risk of clinical worsening or death by 84% compared to placebo for a median follow-up of 32.7 weeks, according to the conference presentation. What's more, sotatercept had a slightly lower discontinuation rate due to treatment-related side effects than placebo patients. 

The new data adds to the company’s initial announcement in October that sotatercept had passed the late-stage test with flying colors. Now, the full depth of what Barr has described as the therapy's "Keytruda-like" potential is coming into view. 

It would be premature to predict sotatercept’s ceiling, however, until data from broader pulmonary hypertension studies pour in. Recruitment is ongoing in the company’s phase 2 CADENCE trial testing sotatercept in a subset of patients with pulmonary hypertension due to heart failure. 

“That'll be the first proof of the pudding about whether this drug might have benefit in a broader proportion of patients with pulmonary hypertension,” said Barr.

In the meantime, Merck will likely accelerate the regulatory process off the heels of the data, with the plan to launch the drug in early 2024. A Merck spokesperson says the company intends to apply for priority review of sotatercept with the FDA. 

 

While sotatercept has accrued much of the acclaim for the cardio team, Barr was also riding the high of positive phase 2 data from the company’s oral PCSK9 inhibitor to treat high cholesterol. The trial compared four doses of MK-0616 in patients with high cholesterol compared to placebo; all four were found to significantly reduce LDL cholesterol levels. 

The highest dose of the med reduced levels of this cholesterol by more than 60% compared to placebo and the number of side effects across all dose levels was consistent with placebo. 

The data is naturally a critical checkpoint as Barr and Merck tout the value of the first oral version of the therapy class currently dominated by Amgen’s Repatha and Regeneron’s Praluent. Next on the clinical docket is a phase 3 trial slated for the second half of the year, but Barr also hopes to launch a cardiovascular outcomes trial before year-end as well. 

The combination of both parcels of new data provides critical validation for Merck’s larger strategy as described by executives. Amid rumors of interest in larger acquisitions like Seagen, Merck has tried to tamp down investor frothing by pointing to more strategic buys—like Acceleron—and internal R&D main courses. Barr says this will likely continue and suggests folks shouldn’t hold their breath for a gargantuan acquisition. 

“What we don't want to do, and what we've shied away from, [are these] massive mergers,” he said. “It’s just so disruptive and silly and difficult.”

Editor's note: This story was updated after a Merck spokesperson clarified that the company plans to apply for priority review of sotatercept with the FDA, but has not yet done so.