
A much-hyped CV drug failed, repeatedly. Now, investors are betting nearly $200M on one last PhIII bid
Just under a decade ago, Eli Lilly announced early results for a new drug that lowered bad cholesterol and raised good cholesterol. It was a “holy grail” result, as JAMA put it in a press release, offering a path for a pill that could curb cardiovascular disease, still the leading cause of death in the US. Merck, Amgen, Roche, and Pfizer all jumped in with similar molecules.
And then, beginning in 2015, it all fell apart. The molecules, known as CETP inhibitor, boosted good cholesterol but pivotal study after pivotal study showed they didn’t prevent heart attacks, strokes or other cardiovascular deaths. “CETP inhibitor class finally dies,” ran one 2017 headline, when Merck abandoned its effort.
Now a group of investors has decided to make one last large bid at resurrecting the field. The lengthy syndicate, led by Morningside Ventures and Forbion, has put $196 million into a Series A for NewAmsterdam Pharma, a small Dutch startup that will take Amgen’s old molecule and push it into Phase III later this year.
The new effort centers around one of the only CETP blockers that didn’t make it into pivotal studies. In 2015, months before Lilly’s drug bombed, Amgen paid $300 million upfront and over a billion in milestones to acquire Dezima and its CETP inhibitor obicetrapib. By 2016, they had suspended investment. They put it on the shelf the following year, after Merck waived the white flag.

The new company is led by CSO John Kastelein, one of the scientists who worked on the original obicetrapib trials, and CEO Michael Davidson, who served as CSO of Corvidia Therapeutics before Novo Nordisk bought out the cardio-focused company for upfront $725 million last June.
The two will have to prove that their molecule can work where similar efforts have repeatedly failed.
Davidson, though, says they have good evidence for their approach. Merck’s CETP inhibitor actually succeded in Phase III, but didn’t provide enough benefit for the company to file for approval. Yet new long-term data suggest that, over time, the drug’s benefit increased from a 9% relative risk reduction in preventing cardiac events to a 20% risk reduction.
And he says new genomic data suggest that researchers misunderstood the drug’s mechanism: Investigators originally thought that CETP inhibitors were beneficial because they boosted good cholesterol, HDL, by incredibly high amounts, but they now think that it’s the modest reduction to bad cholesterol, LDL, that drives benefit.
That means you should be targeting the drug in trials to patients with high levels of LDL, Davidson said, which the Big Pharmas didn’t do.
“It’s not CETP inhibition that was the problem,” Davidson told Endpoints News. “It’s the ways drugs were used.”
He also pointed to evidence from early studies that their molecule was better at lowering LDL than others, with fewer side effects. They’ll now get a chance to prove it, with significant funding to push the drug into the notoriously large and expensive trials that cardiovascular trials require. They plan to start those at the end of 2021. They will likely take about two years.
“We have the right drug,” Davidson said. “We have a safe drug.”
Kaiser Foundation Hospitals, BVF Partners L.P., Population Health Partners, LSP Dementia Fund, Peter Thiel, Janus Henderson Investors, Medpace, GL Capital, JVC Investment Partners, and Presight Capital rounded out the syndicate.