[Complimentary] New Amsterdam repositions obicetrapib selectively for advanced cardiovascular disease patients | $NAMS
Assigning a 63.4% overall probability
Given the high expectations of new pharmaceuticals, it’s surprising many drugs receive and may deserve a mulligan, the golf term for a “do over.” Thalidomide originally was introduced in the 1950s as a sedative and then aggressively prescribed for morning sickness in pregnant women. Severe birth defects in thousands of children resulted in the drug being recalled. Yet in the 1990s, researchers successfully resurrected thalidomide to treat cancer and leprosy through its ability to strengthen the immune system.
New Amsterdam Pharma Company N.V.’s obicetrapib does not face the same challenges as thalidomide but it belongs to the cholesteryl ester transfer protein (CETP) inhibitor class of drugs that failed to impress in five phase III trials conducted by Big Pharma. Amgen, Inc. (NASDAQ:AMGN) bought obicetrapib in 2015 and then discarded the drug two years later after a phase III disappointment.
The CETP drugs were designed to block CETP, the glycoprotein that exchanges cholesterol and triglycerides between lipoproteins. When CETP is deficient, high-density lipoprotein (HDL) levels (good cholesterol) are increased and low-density lipoprotein (LDL) levels are decreased. Drug developers believed by modulating CETP the inhibitors could lower LDL levels in patients with cardiovascular disease when added to statin therapy. Unfortunately, the endpoints of the trial designs generally were time to a heart attack and/or mortality. The drugs faltered in those phase III trial designs. New Amsterdam reacquired obicetrapib and set its sights on use of the drug as a distinct, lipid-lowering therapy. We assigns a 63.4 % overall probability New Amsterdam will report positive, topline phase III data from in the phase III Broadway trial.
Key catalysts
Topline data from phase III Broadway trial testing obicetrapib in patients with established atherosclerotic cardiovascular disease
Key catalyst dates
Q4 2024
Overall Probability: 63.4%
Market Demand: 50.0%
Adoption by KOLs: 66.7%
Clinical Trial Progress: 66.7%
Experience & Capital: 70.0%
New Amsterdam describes obicetrapib as a ”preferred LDL lowering therapy to be used in patients at risk of cardiovascular disease for whom existing therapies are not sufficiently effective or well-tolerated.” The company’s most advanced trials test obicetrapib as a lipid mono therapy. In the phase III Brooklyn trial, the drug met its primary endpoint in patients with heterozygous familial hypercholesterolemia (HeFH). Patients in the 352-patient trial, demonstrated a LS (least squares) mean reduction of LDL at 36.3% (p < 0.0001) compared to placebo at day 84. The results were sustained to day 365 with an LS mean LDL reduction of 41.5% (p < 0.0001).
In the phase III Broadway trial, the primary endpoint again is obicetrapib’s ability to reduce LDL compared to the placebo arm at Day 84 with the first secondary outcome measure. Patients in the Broadway trial will have HeFH and/or a history of established advanced atherosclerotic cardiovascular disease (ASCVD). HeFH increases the risk of ASCVD. When untreated, men and women with HeFH have a 30% to 50% risk of a fatal or a nonfatal cardiac event by ages 50 and 60, respectively.
THE EDGE
Patients in both phase III trials of oral obicetrapib will remain on statin therapy at the maximum tolerated dose. In the Broadway trial, the patients’ statin regimen is defined as either atorvastatin at 40 mg or 80 mb or rosuvastatin at 20 mg or 40 mg. Accordingly, obicetrapib again is being tested as a complement to statin therapy but the objective has been changed to demonstrate the drug’s effectiveness to lower LDL, rather than to reduce the frequency and/or time to a heart attack or death.
Statins are an entrenched pharmaceutical option to treat cardiovascular disease. Whether the poor results from past obicetrapib trials were caused by the known problems of statins or obicetrapib will never be known but New Amsterdam appears to be on point by repositioning the drug as an LDL-lowering therapy. More than likely, the label for obicetrapib will call for individual physicians to determine when the drug is appropriate for patients with HeFH and/or ASCVD.
Amgen bought obicetrapib from Dezima, formerly private company based in The Netherlands. New Amsterdam was formed by the previous management of Dezima and Forbion, a co-founding investor of Dezima. New Amsterdam began talks to buy back obicetrapib shortly after the phase III setback at Amgen.
Significantly, New Amsterdam recently appointed Mark C. McKenna and Wouter Joustra to its board. In 2022, McKenna was CEO of Prometheus Biosciences when the company reported compelling clinical results of the company’s immune disease drug PRA-023. Merck (NYSE:MRK) subsequently purchased Prometheus in 2023 for approximately $10.8 billion.
There are no assurances McKenna can work the same terms at New Amsterdam as he did at Prometheus but similarities exist. Both Prometheus and New Amsterdam were advancing drugs in sizeable markets and both had strong data to support safety and effectiveness. Given some of the side effects in the first wave of obicetrapib trials, the safety of the drug reasonably can be questioned. In the New Amsterdam trials, however, patient selection is more precise and the endpoints are aimed at using obicetrapib as an optional adjunctive therapy.
The potential market for obicetrapib now is smaller while the bar for approval may be lower. However, HeFH and/or ASCVD could be the entrée into treating other cardiovascular conditions, rather than the big swing of earlier CETP inhibitors. New Amsterdam is seeking incremental advances
Disclosures
Initiating coverage and a position in NAMS, and may close position prior to or following the expected catalyst date.