Obicetrapib (CETP inhibitor for dyslipidemia)

The wonder drug:

OBICETRAPIB TARGETS ALL ATHEROGENIC LIPOPROTEINS BEYOND LDL-C 2024

In addition to significantly lowering LDL-C by up to 50.8%, Apo B by up to 29.8%, and non-HDL-C by up to 44.4%, in ROSE2 obicetrapib 10 mg monotherapy compared to placebo significantly decreased total LDL-P, small LDL-P, and sdLDL-C by 54.8%, 92.7%, and 30.9%, respectively. A pooled analysis of Lp(a) demonstrated a placebo-corrected reduction of 57.1%. Obicetrapib plus ezetimibe also significantly reduced total LDL-P (-72.1%), small LDL-P (-95.4%), and sdLDL-C (-44.4%), beyond its significant effects on LDL-C (-63.4%), non-HDL-C (-55.6%), and Apo B (-34.4%). Obicetrapib had an adverse event profile similar to placebo, and it was nearly completely eliminated from circulation within 4 weeks after dosing.

Cholesteryl ester transfer protein inhibition: a pathway to reducing risk of morbidity and promoting longevity 2024

Although the mechanisms are incompletely understood, evidence is mounting for a benefit of CETP inhibition on reducing the risks of type 2 diabetes mellitus and dementia, and most recent data point to an improvement of high-density lipoprotein structure and functionality.
Recent evidence suggests favorable associations between CETP inhibition and reduced risks of several other conditions including age-related macular degeneration, chronic kidney disease, and septicemia.
The increased prevalence of CETP loss-of-function gene variants in centenarians, as well as the potential benefits of CETP inhibition in ASCVD and other conditions associated with aging, suggest lifelong low levels of CETP activity may promote longevity.

When will it be approved?!

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According to NA’s recent presentation, not for a couple more years -

https://ir.newamsterdampharma.com/static-files/e391b584-1a46-45f2-9af8-dbd415d71516

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Thanks!

However this suggests it might be approved earlier based on “LDL-C data 2024E”:

So 2025 at the earliest, otherwise 2026/2027 (or never it trials fail).

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Cross your fingers for an earlier approval date.

Honestly, if you are controlling your lipids through other meds, you can probably wait the 1-3 years for it to get approved.

Waiting for it to be generically available in India might take the longest. Do we know how long it takes from FDA approval until India makes a generic of a drug? 6 months? A year? Years???

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Other meds don’t lower Lp(a) (PCSK9 only a bit) and they don’t eliminate small LDL-P by 95%: Obicetrapib (CETP inhibitor for dyslipidemia) - #52 by adssx

If confirmed, the reduced risk of T2D and dementia would be amazing.

Still worth waiting for the MACE data in 2026.

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NewAmsterdam Pharma to Participate in Upcoming Medical and Investor Conferences in November

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I don’t think it’s so straightforward. Bempedoic Acid is an outlier. I think the BA patent already expired in India, or there is some other reason why it wasn’t granted. In general, India also follows patent terms before generics can be authorized. So, it’s not as though ever drug will launch as a generic in India right away. The difference is that India doesn’t bend over completely for pharma companies and won’t entertain frivolous patent extensions and is perhaps more reserved in granting patents to begin with. Semaglutide’s patent expires in India and China in 2026. It’ll be interesting to see how the market shapes up for that.

You may be right — but the consumer may get lucky. GlobalData, which describes itself as “a leading data and analytics company,” noted in 2022 that “In February 2020, the FDA approved Esperion’s bempedoic acid under the brand name Nexletol and EMA approved it in April 2020 under the brand name Nilemdo.” “Zydus Lifesciences launched a first-in-class oral, non-statin lipid-lowering drug, bempedoic acid, under the brand name Bemdac, for the first time in India in May 2022” and “Within eight days of the launch by Zydus Lifesciences, three companies Sun Pharma, Akum Drugs & Pharmaceuticals Ltd and Cadila Pharma have already announced plans to launch bempedoic acid in India.” " Notably, there are no generics available for bempedoic acid in the US or Europe." “Indian players can launch bempedoic acid in India as there is no valid product patent in India." “Furthermore, none of the Indian players have any partnership with Esperion for bempedoic acid.” “Bempedoic acid has a huge potential in India, based on the overall dyslipidemia patient population and the patients with uncontrolled LDL-c levels.”

This Indian government IP site lists two patents for obi: “OBICETRAPIB FOR TREATMENT OF DEMENTIAS” and “COMBINATION THERAPY OF OBICETRAPIB AND EZETIMIBE FOR USE IN STATIN INTOLERANT PATIENTS”.
https://iprsearch.ipindia.gov.in/PublicSearch/PublicationSearch/Search

If that’s exhaustive, it might mean that Indian pharmas could sell generic obi monotherapy for lipid-lowering whenever they chose to.

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Now peer-reviewed and published: Lower activity of cholesteryl ester transfer protein (CETP) and the risk of dementia: a Mendelian randomization analysis | Alzheimer's Research & Therapy | Full Text

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Nice

Consideration of dementia related traits indicated that lower CETP concentrations were associated higher total brain volume (0.04 per standard deviation, 95%CI 0.02; 0.06), lower risk of LBD (OR 0.81, 95%CI 0.74; 0.89) and Parkinson’s dementia risk (OR 0.26, 95%CI 0.14; 0.48).

That PD OR is incredible

Do you know who that other team is? (Or were you just saying “hopefully will be replicated”?)

It’s PD dementia not PD itself (but still an OK OR for PD, and better than other lipid-lowering therapies).

Ah yes I wasn’t clear and meant “hopefully will be replicated”.

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