LONDON – Five years after offloading it to Amgen Inc. for $300 million, Dutch VC Forbion has reacquired Dezima Pharma BV and its sole product obicetrapib, a cholesterol-lowering drug for patients intolerant to statins. The phase IIb product now forms the basis of Newamsterdam Pharma BV, a startup into which Forbion and co-founders have injected €20 million (US$23.7 million) in seed funding.
The new company is in discussions with the FDA and EMA on the phase III development program and will be raising a “substantial” round before the end of the year.
While it did some work on the synthesis and manufacturing of obicetrapib, Amgen made no headway in clinical development between acquiring the once-daily oral cholesterol ester transferase protein (CETP) inhibitor in September 2015 and axing it in October 2017.
As a result, none of the milestone payments was triggered, said Sander Slootweg, managing partner at Forbion and chair of Newamsterdam.
Amgen is not alone in ditching a CETP program. Indeed, the Thousand Oaks, Calif.-based company blamed its decision on cardiovascular outcomes data from a competitor product. But Slootweg said Forbion and co-investors in Dezima always remained firm believers in obicetrapib.
“When we sold it to Amgen, it was a typically structured deal, with $300 million up front and $1.25 billion in milestones. We’re still waiting for the balance, so when Amgen decided not to pursue development we decided we should try and capture the value and to get a great drug to patients,” Slootweg told BioWorld.
CETP is involved in cholesterol transport. It is responsible for catalyzing the transfer of cholesterol molecules from high-density lipoprotein particles to low-density lipoprotein particles, which eventually contribute to atherosclerosis and to the formation of other lipoproteins.
Slootweg said obicetrapib has the potential to address the market of approximately 32 million people globally whose cholesterol levels are not well-controlled by statins, or who are statin intolerant. “We believe that obicetrapib has megabuster sales potential,” he said.
In the phase IIb 364-patient trial conducted by Dezima, obicetrapib reduced the number of apolipoprotein B-containing particles that constitute LDL-c, with an average lowering of 45 percent at a 5-mg daily dose. The drug was well-tolerated.
The main torch bearer for obicetrapib is John Kastelein, CSO of Dezima and now of Newamsterdam, who is chair of the department of vascular medicine at the Academic Medical Center at the University of Amsterdam. He rescued the drug from the parking lot at Mitsubishi Tanabe Pharma Corp., co-founding Dezima in 2013.
“In my opinion, obicetrapib is a best-in-class CETP inhibitor,” Kastelein said. “We have devised a comprehensive clinical development plan, including a cardiovascular outcomes trial to show all the favorable attributes.”
Amgen’s decision to stop development of obicetrapib came two months after Merck & Co. Inc. reported statistically significant results for its CETP inhibitor anacetrapib at the European Society of Cardiology. Although positive, the effect was rather so-so, showing only a 9% relative risk reduction in an outcomes study involving more than 30,000 patients.
Other casualties in the field include Eli Lilly and Co.’s evacetrapib and Pfizer Inc.’s torcetrapib.
“We’ve taken all the learnings from these other trials and incorporated them into our plans,” Slootweg said. “We don’t intend to make the same mistakes.”
For Newamsterdam, the key lesson from other phase III trials is not to combine CETP inhibitors with high-dose statins, because they interact. Kastelein said this makes obicetrapib an ideal drug for patients who are completely statin intolerant or are on a maximally tolerated but less-than-effective dose.
In the phase IIb trial, obicetrapib reduced LDL-c by up to 69% when combined with a statin; taken alone there were reductions of up to 45%. The outcomes trial Naarden, Netherlands-based Newamsterdam is planning to show if that leads to clinically meaningful reductions in cardiovascular events.
Even at the top the range, in combination with statins, obicetrapib is unlikely to be as effective in reducing LDL-c as antibody-based PCSK9 inhibitors like Amgen’s Repatha (evolocumab) and Sanofi SA/Regeneron Pharmaceuticals Inc.’s Praluent (alirocumab).
In addition to the lower costs and advantages of oral availability, Slootweg said the positioning of obicetrapib will be different. “PCSK9 [inhibitors] focus on people who have already had a heart attack. We will treat patients at risk, who have not had heart disease,” he said.
The financial terms of the acquisition of obicetrapib were not disclosed. However, Slootweg said Newamsterdam has secured rights to the synthesis and manufacturing improvements Amgen had made to the molecule. Mitsubishi Tanabe retains an interest in the product.