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Posted On: 09/05/2024 1:47:50 AM
Post# of 148870
So, speaking of research, I took a look at the citations on that "Expanding the Therapeutic Perspective of CCR5 Blockade" article, and found a couple studies using maraviroc and cenicriviroc for NASH, MASH, MAFLD. I hadn't realized a CCR5 inhibitor had been studied in (I'll call it) MASH before...
Both failed to pass muster. In the AURORA Phase III trial utilizing cenicriviroc "The study did not demonstrate the efficacy of CVC for treating liver fibrosis."
https://pubmed.ncbi.nlm.nih.gov/37061109/.
In the MAVMET trial they tested maraviroc and/or metformin for MAFLD in HIV patients. Primary outcome was change in Liver Fat Fraction after 48 weeks with Mara. “Contrary to our hypothesis, neither Mara or Met, or the combination significantly reduced liver fat. They added the caveat that “Baseline levels of liver fat were lower than predicted.”
https://pubmed.ncbi.nlm.nih.gov/38819839/
Now, I know from Cytodyn’s study of LL in MASH (from the HEATMAP!) that it decreases inflammation in the liver, and reduces fat, but what are the indications that it can deal with fibrosis? Ohm—or any other knowledgable person out there—any data that would suggest a resolution in fibrosis? Clearly, the other two CCR5 inhibitors failed. And this is the kind of thing that could keep me up at night...
Continuing on the NASH/MASH topic, and Cytodyn's place in the landscape, I am concerned the GLP-1 drugs are going to expand into indications like reducing liver fat and addressing general, low-grade inflammation. I read something to the effect that 10% weight reduction leads to a reduction in fibrosis, which would imply that a reasonable loss of body mass will ameliorate the fibrotic liver. They are sure getting a lot of press these days in the Metabolic Syndrome area, and might sort of steal leronlimabs thunder in the anti-inflammatory and MASH space. And the Big Pharma Overlords have all the money and muscle to dominate our poor little mab.
(There's an absurdist/existential play called "Six Characters in Search of an Author." Pirandello, I believe. I think of leronlimab as the "Mab in search of an Indication." God I hope the MSS mCRC or the HIV/Inflammation trials succeed!).
And back to MASH--in terms of other little biotechs, Altimune's pemvidutide--a GLP-1/glucagon dual receptor agonist being tested for weight loss and MASLD--reduced fibrosis in mice. And as noted they are developing it for the MASH space, with Phase IIb results due 1st quarter 2025. AI says chances are good that it can take down fibrosis a notch. So we do have some serious competition above and beyond Madrigal. But if we can show fibrotic reduction we would have an edge... Any thoughts/comments on the above?
Both failed to pass muster. In the AURORA Phase III trial utilizing cenicriviroc "The study did not demonstrate the efficacy of CVC for treating liver fibrosis."
https://pubmed.ncbi.nlm.nih.gov/37061109/.
In the MAVMET trial they tested maraviroc and/or metformin for MAFLD in HIV patients. Primary outcome was change in Liver Fat Fraction after 48 weeks with Mara. “Contrary to our hypothesis, neither Mara or Met, or the combination significantly reduced liver fat. They added the caveat that “Baseline levels of liver fat were lower than predicted.”
https://pubmed.ncbi.nlm.nih.gov/38819839/
Now, I know from Cytodyn’s study of LL in MASH (from the HEATMAP!) that it decreases inflammation in the liver, and reduces fat, but what are the indications that it can deal with fibrosis? Ohm—or any other knowledgable person out there—any data that would suggest a resolution in fibrosis? Clearly, the other two CCR5 inhibitors failed. And this is the kind of thing that could keep me up at night...
Continuing on the NASH/MASH topic, and Cytodyn's place in the landscape, I am concerned the GLP-1 drugs are going to expand into indications like reducing liver fat and addressing general, low-grade inflammation. I read something to the effect that 10% weight reduction leads to a reduction in fibrosis, which would imply that a reasonable loss of body mass will ameliorate the fibrotic liver. They are sure getting a lot of press these days in the Metabolic Syndrome area, and might sort of steal leronlimabs thunder in the anti-inflammatory and MASH space. And the Big Pharma Overlords have all the money and muscle to dominate our poor little mab.
(There's an absurdist/existential play called "Six Characters in Search of an Author." Pirandello, I believe. I think of leronlimab as the "Mab in search of an Indication." God I hope the MSS mCRC or the HIV/Inflammation trials succeed!).
And back to MASH--in terms of other little biotechs, Altimune's pemvidutide--a GLP-1/glucagon dual receptor agonist being tested for weight loss and MASLD--reduced fibrosis in mice. And as noted they are developing it for the MASH space, with Phase IIb results due 1st quarter 2025. AI says chances are good that it can take down fibrosis a notch. So we do have some serious competition above and beyond Madrigal. But if we can show fibrotic reduction we would have an edge... Any thoughts/comments on the above?
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