UPDATED: NewAmsterdam Pharma resurrects Amgen's old CETP drug with plans to jump into PhIII this year
Eli Lilly thought it found the “holy grail” a decade ago with a CETP inhibitor that lowered bad cholesterol and raised good cholesterol, with others like Merck, Amgen, Roche and Pfizer jumping in the race as well. But when study after study showed the new class of drugs didn’t curb cardiovascular disease, Big Pharma largely abandoned their efforts.
NewAmsterdam Pharma CEO Michael Davidson saw an opportunity last year to resurrect Amgen’s old drug — one of the few that didn’t make it to pivotal studies. And on Wednesday, he unveiled the first positive Phase II results.
When administered along with statins, a 10 mg dose regimen of obicetrapib lowered patients’ bad cholesterol (LDL) levels by a median 51% compared to 7% in the placebo arm, meeting the study’s primary endpoint, Davidson said, hitting a p-value of p=0.0001. Mean decrease in LDL cholesterol was 44% in the obicetrapib arm, versus 4% in the placebo arm, according to the company, a difference which hit a p-value of p<0.0001.
“We learned a lot from those failures,” he said of other CETP attempts. “And now we have a much more effective LDL-lowering drug, more than twice as effective in lowering LDL, and also based on our data so far (it’s) extremely safe.”
Davidson suggested that prior researchers misunderstood the drug’s mechanism: While investigators previously thought CETP inhibitors were beneficial because they boosted good cholesterol (HDL) by large amounts, they now think it’s the reduction to bad cholesterol that leads to benefit.
All 120 patients in the Phase II trial, dubbed ROSE, were already taking maximal doses of high-intensity statins, which work by blocking a substance your body needs to make cholesterol, Davidson said. Patients were divided into three cohorts: a 5 mg group, a 10 mg group, and a placebo group. Both dose groups met the primary endpoint, according to Davidson, who’s working to initiate Phase III trials in Q4. They’re also planning to test obicetrapib in combination with the already approved cholesterol-lowering drug ezetimibe.
“We proved that it’s just as effective, if not more effective, on top of high-intensity statins. So that’s exactly the type of patient population that the FDA wants to see for future development of LDL-c-lowering therapies,” he said.
Amgen shelled out $300 million upfront and over $1 billion in milestones to buy out Dezima Pharma and its sole product, obicetrapib, back in 2015. But the pharma ended up shelving the candidate just two years later, shortly after Eli Lilly, Pfizer, Roche and Merck all walked away from their own CETP drugs.
Last August, Davidson snagged the candidate from Amgen for an undisclosed amount. If he could flip it around for an FDA OK, he said at the time, it would be the “crowning” achievement of his career. In January, a lengthy syndicate led by Morningside Ventures and Forbion put $196 million into a Series A to get the company started.
If all goes well, NewAmsterdam thinks obicetrapib could treat diseases like Alzheimer’s and diabetes. The team is planning to kick off an Alzheimer’s trial in September, and they’ll evaluate diabetes endpoints throughout the upcoming Phase III program.
“We feel we really have the right drug, the right compound that now can fully validate what’s already been genetically validated as a target to lower LDL and cardiovascular risk,” Davidson said.
This article has been updated to include more data provided by NewAmsterdam.