MK-0616 may soon be obtainable from China — it's a PCSK9 inhibitor; looking for science-minded input

[jg1979]

This peptide could hit the market before long! What would the dosing look like? 40mg per day? Or a lower amount when injected? Any details would be greatly appreciated!

 

[FartfulCodger]

That would be a big deal. Fingers crossed it pans out!

The phase 2b writeup says participants were randomised on a 1:1:1:1:1 basis to MK-0616 at 6 mg, 12 mg, 18 mg, or 30 mg once daily, or to a matching placebo.

Link: https://www.jacc.org/doi/10.1016/j.jacc.2023.02.018

 

[Jfrick11]

jg1979 said:

This peptide could hit the market before long! What would the dosing look like? 40mg per day? Or a lower amount when injected? Any details would be greatly appreciated!

It works by inhibiting PCSK9, and injection isn't the route here. What we're talking about is an oral formulation of the injectable that already exists on the market. Since the injectable carries an enormous price tag, an oral option would deliver major gains in both ease of use and affordability.

Phase 2 trials evaluated 6, 12, 18, or 30 mg taken once per day. Every one of those arms produced clinically meaningful drops in LDL-C and ApoB, with placebo-adjusted reductions exceeding 55% at the 12 mg and higher doses. MK-0616 had a well-tolerated profile, and no overall patterns in AEs emerged across the treatment groups.

Phase 3 is underway, with a 20mg dose as the target.

 

[jg1979]

Jfrick11 said:

jg1979 said:

This peptide could hit the market before long! What would the dosing look like? 40mg per day? Or a lower amount when injected? Any details would be greatly appreciated!

It works by inhibiting PCSK9, and injection isn't the route here. What we're talking about is an oral formulation of the injectable that already exists on the market. Since the injectable carries an enormous price tag, an oral option would deliver major gains in both ease of use and affordability.

Phase 2 trials evaluated 6, 12, 18, or 30 mg taken once per day. Every one of those arms produced clinically meaningful drops in LDL-C and ApoB, with placebo-adjusted reductions exceeding 55% at the 12 mg and higher doses. MK-0616 had a well-tolerated profile, and no overall patterns in AEs emerged across the treatment groups.

Phase 3 is underway, with a 20mg dose as the target.

Yeah, I noticed that afterward. However, no one offers it as an injectable, and the Chinese vendors still don't carry the injectable form. They're leaving a lot of money on the table, though. Plenty of us who are genetically predisposed to elevated LDL would start using it immediately!

 

[Bioexplorer]

J

jg1979 said:

Jfrick11 said:

jg1979 said:

This peptide could hit the market before long! What would the dosing look like? 40mg per day? Or a lower amount when injected? Any details would be greatly appreciated!

It works by inhibiting PCSK9, and injection isn't the route here. What we're talking about is an oral formulation of the injectable that already exists on the market. Since the injectable carries an enormous price tag, an oral option would deliver major gains in both ease of use and affordability.

Phase 2 trials evaluated 6, 12, 18, or 30 mg taken once per day. Every one of those arms produced clinically meaningful drops in LDL-C and ApoB, with placebo-adjusted reductions exceeding 55% at the 12 mg and higher doses. MK-0616 had a well-tolerated profile, and no overall patterns in AEs emerged across the treatment groups.

Phase 3 is underway, with a 20mg dose as the target.

Yeah, I noticed that afterward. However, no one offers it as an injectable, and the Chinese vendors still don't carry the injectable form. They're leaving a lot of money on the table, though. Plenty of us who are genetically predisposed to elevated LDL would start using it immediately!

Yes — for managing lipids, evolocumab has worked better than anything else I've personally used. Switching off a statin brought LDL down roughly 30% and triglycerides roughly 50%. The problem is the price, which stays high even when insurance is decent, and every year the reapproval process is a nightmare because insurers are awful.

There's some guilt in sourcing unlicensed drugs that are still patent-protected, though I think I could live with it if a low-cost copy showed up on the "gray" market. That said, I don't see it happening soon: this is a big, complicated protein, unlike a basic 39-amino-acid peptide. Oh well.

What I'm wondering is whether retatrutide's lipid effects would stack with Repatha, or whether Reta works via the same PCSK9 inhibition route and therefore adds little. I might have an answer in a couple of months.

 

[CathyGoesFar]

Bioexplorer said:

J

jg1979 said:

Jfrick11 said:

jg1979 said:

This peptide could hit the market before long! What would the dosing look like? 40mg per day? Or a lower amount when injected? Any details would be greatly appreciated!

It works by inhibiting PCSK9, and injection isn't the route here. What we're talking about is an oral formulation of the injectable that already exists on the market. Since the injectable carries an enormous price tag, an oral option would deliver major gains in both ease of use and affordability.

Phase 2 trials evaluated 6, 12, 18, or 30 mg taken once per day. Every one of those arms produced clinically meaningful drops in LDL-C and ApoB, with placebo-adjusted reductions exceeding 55% at the 12 mg and higher doses. MK-0616 had a well-tolerated profile, and no overall patterns in AEs emerged across the treatment groups.

Phase 3 is underway, with a 20mg dose as the target.

Yeah, I noticed that afterward. However, no one offers it as an injectable, and the Chinese vendors still don't carry the injectable form. They're leaving a lot of money on the table, though. Plenty of us who are genetically predisposed to elevated LDL would start using it immediately!

Yes — for managing lipids, evolocumab has worked better than anything else I've personally used. Switching off a statin brought LDL down roughly 30% and triglycerides roughly 50%. The problem is the price, which stays high even when insurance is decent, and every year the reapproval process is a nightmare because insurers are awful.

There's some guilt in sourcing unlicensed drugs that are still patent-protected, though I think I could live with it if a low-cost copy showed up on the "gray" market. That said, I don't see it happening soon: this is a big, complicated protein, unlike a basic 39-amino-acid peptide. Oh well.

What I'm wondering is whether retatrutide's lipid effects would stack with Repatha, or whether Reta works via the same PCSK9 inhibition route and therefore adds little. I might have an answer in a couple of months.

I have familial hypercholesterolemia and take both reta and Repatha. While on reta alone, my LDL did not decrease, and the reduction I've experienced with Repatha matches what is typically expected.

 

[Bioexplorer]

CathyGoesFar said:

Bioexplorer said:

J

jg1979 said:

Jfrick11 said:

jg1979 said:

This peptide could hit the market before long! What would the dosing look like? 40mg per day? Or a lower amount when injected? Any details would be greatly appreciated!

It works by inhibiting PCSK9, and injection isn't the route here. What we're talking about is an oral formulation of the injectable that already exists on the market. Since the injectable carries an enormous price tag, an oral option would deliver major gains in both ease of use and affordability.

Phase 2 trials evaluated 6, 12, 18, or 30 mg taken once per day. Every one of those arms produced clinically meaningful drops in LDL-C and ApoB, with placebo-adjusted reductions exceeding 55% at the 12 mg and higher doses. MK-0616 had a well-tolerated profile, and no overall patterns in AEs emerged across the treatment groups.

Phase 3 is underway, with a 20mg dose as the target.

Yeah, I noticed that afterward. However, no one offers it as an injectable, and the Chinese vendors still don't carry the injectable form. They're leaving a lot of money on the table, though. Plenty of us who are genetically predisposed to elevated LDL would start using it immediately!

Yes — for managing lipids, evolocumab has worked better than anything else I've personally used. Switching off a statin brought LDL down roughly 30% and triglycerides roughly 50%. The problem is the price, which stays high even when insurance is decent, and every year the reapproval process is a nightmare because insurers are awful.

There's some guilt in sourcing unlicensed drugs that are still patent-protected, though I think I could live with it if a low-cost copy showed up on the "gray" market. That said, I don't see it happening soon: this is a big, complicated protein, unlike a basic 39-amino-acid peptide. Oh well.

What I'm wondering is whether retatrutide's lipid effects would stack with Repatha, or whether Reta works via the same PCSK9 inhibition route and therefore adds little. I might have an answer in a couple of months.

I have familial hypercholesterolemia and take both reta and Repatha. While on reta alone, my LDL did not decrease, and the reduction I've experienced with Repatha matches what is typically expected.

I appreciate that data point. I had hoped Reta would give extra benefit, but should that not happen, I might discontinue Repatha in order to observe what Reta does by itself. When my brother moved from 15mg Tirz to 15mg Reta, his lipids improved dramatically. And yes, I realize that exceeds the maximum Reta dose used in trials.

 

[jg1979]

Bioexplorer said:

CathyGoesFar said:

Bioexplorer said:

J

jg1979 said:

Jfrick11 said:

jg1979 said:

This peptide could hit the market before long! What would the dosing look like? 40mg per day? Or a lower amount when injected? Any details would be greatly appreciated!

It works by inhibiting PCSK9, and injection isn't the route here. What we're talking about is an oral formulation of the injectable that already exists on the market. Since the injectable carries an enormous price tag, an oral option would deliver major gains in both ease of use and affordability.

Phase 2 trials evaluated 6, 12, 18, or 30 mg taken once per day. Every one of those arms produced clinically meaningful drops in LDL-C and ApoB, with placebo-adjusted reductions exceeding 55% at the 12 mg and higher doses. MK-0616 had a well-tolerated profile, and no overall patterns in AEs emerged across the treatment groups.

Phase 3 is underway, with a 20mg dose as the target.

Yeah, I noticed that afterward. However, no one offers it as an injectable, and the Chinese vendors still don't carry the injectable form. They're leaving a lot of money on the table, though. Plenty of us who are genetically predisposed to elevated LDL would start using it immediately!

Yes — for managing lipids, evolocumab has worked better than anything else I've personally used. Switching off a statin brought LDL down roughly 30% and triglycerides roughly 50%. The problem is the price, which stays high even when insurance is decent, and every year the reapproval process is a nightmare because insurers are awful.

There's some guilt in sourcing unlicensed drugs that are still patent-protected, though I think I could live with it if a low-cost copy showed up on the "gray" market. That said, I don't see it happening soon: this is a big, complicated protein, unlike a basic 39-amino-acid peptide. Oh well.

What I'm wondering is whether retatrutide's lipid effects would stack with Repatha, or whether Reta works via the same PCSK9 inhibition route and therefore adds little. I might have an answer in a couple of months.

I have familial hypercholesterolemia and take both reta and Repatha. While on reta alone, my LDL did not decrease, and the reduction I've experienced with Repatha matches what is typically expected.

I appreciate that data point. I had hoped Reta would give extra benefit, but should that not happen, I might discontinue Repatha in order to observe what Reta does by itself. When my brother moved from 15mg Tirz to 15mg Reta, his lipids improved dramatically. And yes, I realize that exceeds the maximum Reta dose used in trials.

So, here's the situation. I've been using Reta, and when I got my bloodwork done on July 7th, my ApoB had gone down by 37 points while my LDL fell by 54 points. The previous panel was from February, and I began Reta in May. These labs were run via Function Health. It appears the intended outcome was achieved. My ApoB remains a bit elevated, but at a weekly dose of 1mg, my overall cholesterol numbers look excellent.