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Akero data shocks the MASLD/MASH community

Akero releases topline results from its phase 2B trial of 96 weeks of efruxifermin (EFX) treatment in patients with pre-cirrhotic MASH to a surprised community.

First looks suggest that Akero sets a new standard for what is possible in the treatment of liver fibrosis.  While any potential drug approval is still years away, the HARMONY trial indicates that NASH/MASH fibrosis will be treatable with drugs.

EFX is an agonist, a molecule that stimulates the production of the hormone FGF21 which has long been recognized as a potential treatment target with several research efforts working on it. The chart below illustrates how the new data compares to some other molecules under development.


For the science minded a brief overview.

FGF21 (fibroblast growth factor 21) is a hormone that is produced by the liver and adipose tissue. It has a variety of metabolic effects, including:

* **Glucose metabolism:** FGF21 increases insulin sensitivity and glucose uptake in skeletal muscle and adipose tissue. This helps to lower blood sugar levels.
* **Lipid metabolism:** FGF21 decreases lipogenesis (fatty acid synthesis) and increases lipolysis (fatty acid breakdown). This helps to lower triglyceride levels and increase HDL cholesterol levels.
* **Energy expenditure:** FGF21 increases energy expenditure by promoting the browning of white adipose tissue. Brown adipose tissue is a type of fat that burns calories to produce heat.

* **Anti-inflammatory effects:** FGF21 has anti-inflammatory effects in both adipose tissue and the liver.
* **Cardioprotective effects:** FGF21 has cardioprotective effects, including reducing blood pressure and improving heart function.
* **Neuroprotective effects:** FGF21 has neuroprotective effects, including reducing neuronal damage and improving cognitive function.

Its liver specific functions include:

Inhibition of gluconeogenesis: FGF21 inhibits gluconeogenesis, the process by which the liver produces glucose from non-carbohydrate sources. This helps to lower blood sugar levels.
Stimulation of fatty acid oxidation: FGF21 stimulates fatty acid oxidation in the liver. This helps to lower triglyceride levels and increase HDL cholesterol levels.
Inhibition of lipogenesis: FGF21 inhibits lipogenesis, the process by which the liver produces fatty acids. This helps to reduce the accumulation of fat in the liver.
Anti-inflammatory effects: FGF21 has anti-inflammatory effects in the liver. It reduces the production of pro-inflammatory cytokines and increases the production of anti-inflammatory cytokines.
Hepatoprotective effects: FGF21 has hepatoprotective effects, including reducing liver damage and fibrosis.

Overall, FGF21 is a hormone that helps to regulate metabolism and improve insulin sensitivity. It has potential therapeutic applications for the treatment of obesity, type 2 diabetes, and other metabolic disorders.

One of the things that has made FGF21 so appealing is that it is a normal molecule of the body.  By increasing the activity of that system, the opportunity exists to improve the beneficial effects of the hormone without introducing new molecules that may have unwanted side effects.

Akero is the first to convincingly demonstrate the potential of this line of drug development. Don't get too excited as this is a Phase 2b trial.  There is a long way to go before any potential drug could be approved but it demonstrates that fibrosis can be treated.  

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