Yes, of course.
I don’t think that clinicians (and behind them, most importantly, payers, so private insurers in the US and governments in the rest of the world) care about ACM. (Unfortunately) I assume that if obicetrapib 1/ reduces LDL as much as statins, 2/ reduces MACE as much as statins, 3/ is associated with fewer side effects and increased adherence, and 4/ costs less than PCSK9i then it’ll persuade clinicians.
PREVAIL trial not scheduled to complete until end of 2026.
So not on market until 2027?
Or would they be able to market in 2025, based on the other phase 3’s that complete by then?
PowerPoint presentation, New insights on CETP inhibition from genetic research and clinical trials, Kastelein, 2023
They should be. These trials are for different indications I think. So obicetrapib could first be approved for HeFH in early 2025 for instance.
Seems their LDL-C concentration is on slightly higher than optimal.
I don’t understand: who are the controls? and these are the HDL and LDL concentrations at which age? at death?
Does anyone know if CETP enzyme can be tested?
@adssx below you find transcript that goes with the powerpoint presentation.
new_insights_on_CETP_inhibition_from_genetic_research_and_clinical_trials.pdf (55.6 KB)
Mendelian randomization, have looked at this in depth, just skimmed the slides after @AnUser shared them.
First slide I pasted above seems to show which variants they are comparing.
This slides also helps with some form of dose response.
Hopefully they will publish it soon (if not already?) and any details not explained in the transcript will hopefully be more clear
Just published: Obicetrapib as an Adjunct to Stable Statin Therapy in Japanese Subjects: Results from a Randomized Phase 2 Trial
This double-blind, randomized, phase 2 trial examined obicetrapib 2.5, 5, and 10 mg/d, compared with placebo, for 8 weeks as an adjunct to stable statin therapy (atorvastatin 10 or 20 mg/d or rosuvastatin 5 or 10 mg/d) in Japanese men and women who had not achieved 2022 Japan Atherosclerosis Society Guidelines and had LDL-C ＞70 mg/dL or non-high-density lipoprotein cholesterol (non-HDL-C) ＞100 mg/dL and triglycerides (TG) ＜400 mg/dL.
In the 102 randomized subjects (mean age 64.8 y, 71.6% male), obicetrapib significantly lowered median LDL-C, apoB, and non-HDL-C, and raised HDL-C at all doses; responses in the obicetrapib 10 mg group were -45.8%, -29.7%, -37.0%, and +159%, respectively (all p＜0.0001 vs. placebo).
Fewer adverse events than placebo, especially for the lower doses:
Treatment-emergent adverse events (TEAEs) were reported by 47 (46.1%) of the 102 participants: 15 (57.7%) in placebo, 9 (36.0%) in obicetrapib 2.5 mg, 8 (32.0%) in obicetrapib 5 mg, and 15 (57.7%)
On Sunday, NewAmsterdam Pharma will present new results as well: 1433-211 / 211 - SYNERGISTIC EFFECT OF OBICETRAPIB AND EZETIMIBE ON CIRCULATING LDL PARTICLES
Can’t wait!
Do we know what the impact on Lp(a) was?
They didn’t measure it (see full text):
Another potential limitation of this study was that it did not measure the effects of obicetrapib on the concentrations of lipoprotein particles or lipoprotein(a) among Japanese subjects. In the Study to Evaluate the Effect of Obicetrapib in Combination with Ezetimibe as an Adjunct to High Intensity Statin Therapy, 10 mg obicetrapib in combination with 10 mg ezetimibe significantly reduced total and small LDL particles by 72% and 95%, respectively, and altered the HDL profile in a manner suggesting it increased cholesterol flux through the HDL fraction. The results from the Randomized Study of Obicetrapib as an Adjunct to Statin Therapy also indicated that 10 mg obicetrapib on top of highintensity statin reduced lipoprotein(a) by 56.5%. In addition to the ongoing cardiovascular outcome trial of obicetrapib mentioned previously, PREVAIL, three other phase 3 trials of obicetrapib are underway, as well as several phase 1 and 2 trials designed to further investigate the effects of obicetrapib on lipoprotein metabolism, and its safety and PK profile in various populations.
ROSE2 met its primary and secondary endpoints, with statistically significant and clinically meaningful reductions in LDL-C and apolipoprotein B (“ApoB”) observed. Statistically significant improvements in lipoprotein(a) (“Lp(a)”), non-HDL cholesterol (“non-HDL-C”) and total and small LDL particles were also observed. In addition, the combination of obicetrapib and ezetimibe was observed to be well-tolerated, with a safety profile observed to be comparable to placebo. With these data in hand, the Company has selected a formulation for a fixed-dose combination tablet and intends to advance the compound into a Phase 3 trial in the first quarter of 2024.
That’s from 2023, nothing new, we already know it decreases LDL etc.
Yes, they mostly repeated results already given in the 2023 paper published in the Journal of Clinical Lipidology.
However, they gave one more result not present in the 2023 paper: “In addition, we observed a median reduction in Lp(a) of 47.2% and 40.2% in the monotherapy and combination arms, respectively.” 
They didn’t give total cholesterol, so I calculated it as HDL-C + NON-HDL-C (in mg/dL):
Very nice 
perhaps the talk at the conference will share additional info too
Nothing, unfortunately, it was just marketing: https://twitter.com/ErinMichos/status/1777085891338735870
Kastelein gave additional information on Twitter, though:
BROOKLYN and TANDEM don’t seem to measure MACE, so I’m surprised. BROADWAY (2,532 participants) does, though:
So, in any case, we’ll have MACE data for obicetrapib by the end of this year. If extremely positive, approval next year? 
(“Looking at individual stages of the process, the averages were 2.3 years for Phase I, 3.6 years for Phase II, 3.3 years for Phase III, and 1.3 years between Phase III and regulatory approval.” [source])
From the phase 2 trial, I understand that obicetrapib (alone or with ezetimibe):
Is this good? A quick search led me to several papers finding an association between higher levels of small HDL and better long-term outcomes:
Or did I misunderstand something?
