Emerging Weight Loss Medicines: Investigational Drug Targets Under Study

What happens when researchers look beyond GLP 1 medicines and ask whether other hormones could change the way the body handles fat and energy?

That is where efruxifermin comes into the picture.

Efruxifermin is an investigational medicine designed to mimic the activity of fibroblast growth factor 21, or FGF21, a natural hormone involved in metabolic regulation. It is being developed primarily as a potential treatment for metabolic dysfunction associated steatohepatitis, known as MASH, rather than as a licensed weight loss medicine.

Efruxifermin has not been granted a marketing authorisation in the UK. It is currently being studied in Phase 3 clinical trials, so it is not a medicine that can be routinely prescribed or bought for weight management. Akero Therapeutics, the company developing efruxifermin, describes it as an investigational treatment for MASH.

Its mechanism is also different from that of GLP 1 medicines. Efruxifermin is designed to activate the FGF21 pathway, which is involved in fat, glucose and energy metabolism. This makes it scientifically interesting, particularly in research into MASH and other metabolic conditions, but an interesting mechanism is not the same as a proven or licensed treatment.

This guide looks at how efruxifermin works, why FGF21 has attracted interest, what researchers are studying it for, what clinical trials have shown so far and what remains unknown.

Key things to know

• Efruxifermin is an investigational medicine and is not currently licensed for routine use in the UK.
• It is designed to mimic the activity of FGF21, rather than acting through the GLP 1 pathway.
• Its main clinical development programme is focused on MASH, a metabolic liver disease.
• Efruxifermin is being studied in an ongoing Phase 3 programme called SYNCHRONY.
• Earlier clinical studies have reported changes in liver fat and fibrosis measures, but these results do not establish that efruxifermin is a licensed weight loss treatment.
• Long term safety and effectiveness are still being studied.
• Current licensed weight management medicines are a separate category and have been assessed by regulators for their authorised uses. The MHRA lists several licensed GLP 1 medicines, including semaglutide, tirzepatide and liraglutide.

What Does "Emerging Weight Loss Medicines" Actually Mean?

The phrase can be misleading.

An emerging medicine is not necessarily a medicine that is about to appear in pharmacies. It may still be in early or late stage clinical research, and researchers may be investigating it for a condition other than weight management.

Drug development involves several stages of laboratory research and clinical trials before regulators can decide whether a medicine should be authorised. Even when an investigational medicine produces encouraging results, later trials may produce different findings.

Efruxifermin is a good example. Its current development programme is focused on MASH, while its effects on metabolic measures such as liver fat and body weight have also been studied.

Why are researchers studying new drug targets?

GLP 1 is only one of several biological pathways involved in appetite, energy use, glucose control and fat metabolism.

Researchers are therefore studying other pathways that could potentially affect metabolic diseases. Some investigational medicines are designed to act on a single pathway, while others combine more than one mechanism.

FGF21 is one of these research areas. It is a naturally occurring hormone involved in several aspects of metabolism, which has made it a target for drug development.

The important distinction is that a biological pathway can be scientifically promising without an investigational medicine being proven safe and effective for routine use.

Efruxifermin is not currently available as a routine medicine

Efruxifermin has not received a marketing authorisation from the MHRA. The MHRA's own records list efruxifermin as an investigational substance being studied for MASH, while Akero's current information confirms that its Phase 3 SYNCHRONY programme is ongoing.

This means efruxifermin is not available as a routinely prescribed weight management medicine in the UK.

Clinical trial participation is different from getting a prescription. Trial participants have to meet the study's eligibility requirements and go through the formal trial process.

What Is FGF21, the Hormone Behind Efruxifermin?

What does FGF21 do naturally in the body?

FGF21, or fibroblast growth factor 21, is a hormone involved in regulating several metabolic processes.

It is involved in glucose and lipid metabolism and energy balance. FGF21 works through a receptor system involving fibroblast growth factor receptors and the co receptor beta klotho. Research has shown that beta klotho is important for FGF21 signalling through receptors such as FGFR1c and FGFR3c.

This pathway has attracted interest because it connects hormone signalling with processes involved in how the body handles glucose, fat and energy.

That does not mean that simply increasing FGF21 will automatically produce a particular health outcome. Researchers are still working out how best to use this pathway as a medicine.

Why not simply use natural FGF21 as a medicine?

One challenge with using natural FGF21 as a treatment is that it does not remain in the body for long enough to provide a practical, sustained treatment effect.

Efruxifermin was designed to address this problem. It is an engineered version of the FGF21 approach that is intended to remain active in the body for longer.

This type of drug design is one reason researchers can turn a naturally occurring hormone into a potential medicine.

How Does Efruxifermin Work?

How is efruxifermin different from natural FGF21?

Efruxifermin is a bivalent Fc FGF21 analogue. In simple terms, it contains two FGF21 molecules linked to an Fc portion that helps extend how long the medicine remains in the body.

The aim is to maintain FGF21 like signalling for longer than the natural hormone would allow. Akero describes the molecule as being engineered to increase its half life and improve receptor engagement.

Efruxifermin has been administered once weekly by subcutaneous injection in clinical trials, including the Phase 2b HARMONY study.

Which receptors does efruxifermin act on?

Efruxifermin is designed to mimic FGF21 signalling through FGFR1c, FGFR2c and FGFR3c in combination with beta klotho.

These receptors form part of the signalling system through which FGF21 produces its biological effects. When the pathway is activated, signals are passed inside cells and can influence metabolic processes.

The science can sound complicated, but the basic idea is fairly straightforward: efruxifermin is designed to copy an existing hormone signal rather than introduce an entirely new biological pathway.

What does agonist mean?

You may see the word "agonist" used when reading about efruxifermin.

An agonist is a substance that binds to a receptor and activates it. In this case, efruxifermin is designed to activate the FGF21 receptor pathway in a way that mimics the activity of the body's natural hormone.

How is this different from GLP 1 medicines?

GLP 1 medicines work through the GLP 1 pathway. They can help people feel fuller and are used for specific conditions, including weight management and type 2 diabetes depending on the medicine. Some newer medicines, such as tirzepatide, also act on another hormone pathway.

Efruxifermin works through the FGF21 pathway instead.

Research into FGF21 suggests that the pathway can affect energy expenditure, glucose metabolism and fat metabolism. However, this does not mean that efruxifermin should be described as a proven alternative to GLP 1 medicines for weight loss.

The two approaches are biologically different, which is one of the reasons researchers are interested in studying them.

What Is Efruxifermin Actually Being Studied For?

Its main focus: MASH

Efruxifermin's current clinical development is focused on MASH, or metabolic dysfunction associated with steatohepatitis.

MASH is a form of metabolic liver disease in which excess fat in the liver is associated with inflammation and liver injury. Over time, some people can develop fibrosis, or scarring, which may progress to cirrhosis.

Efruxifermin is being studied in people with different stages of MASH and liver fibrosis. The current Phase 3 SYNCHRONY programme includes three trials looking at different groups, including people with moderate to advanced fibrosis and people with MASH cirrhosis.

This is important because efruxifermin is not currently a licensed treatment for obesity.

Why does weight come up when discussing efruxifermin?

FGF21 is involved in metabolic processes that include fat and energy metabolism. As a result, researchers have measured body weight and other metabolic outcomes in some studies.

However, these findings should be kept in context.

A medicine being studied for MASH can produce changes in body weight without being a weight management medicine. The condition being treated, the trial design and the main outcomes being measured all matter.

Efruxifermin's current development programme is centred on MASH and liver related outcomes.

What Has Research Found So Far?

What happened in the HARMONY trial?

HARMONY was a randomised, double blind, placebo controlled Phase 2b trial involving adults with biopsy confirmed MASH and stage F2 or F3 liver fibrosis.

Participants received either efruxifermin or placebo, with efruxifermin given once a week by subcutaneous injection. The trial was designed to assess liver related outcomes, including improvement in fibrosis without worsening of MASH.

The initial results showed that some participants receiving efruxifermin achieved the trial's fibrosis improvement endpoint. The 96 week results provided additional data on safety and liver related outcomes, but they do not turn an investigational medicine into an approved treatment.

What about the reported 65% reduction in liver fat?

This figure needs some context.

A 65% reduction in hepatic fat fraction was reported in a separate 12 week Phase 2 study that looked at efruxifermin added to a GLP 1 receptor agonist in people with MASH and type 2 diabetes. The study compared the combination with GLP 1 receptor agonist treatment alone.

It would therefore be misleading to present the 65% figure as a general weight loss result or as a result from the HARMONY trial.

This is an important distinction when reading early drug research. A percentage from one specific trial does not automatically predict what will happen in another group of patients or in routine clinical practice.

What is the SYNCHRONY programme?

SYNCHRONY is Akero's ongoing Phase 3 clinical development programme for efruxifermin.

It consists of three randomised, placebo controlled trials:

• SYNCHRONY Histology is studying people with biopsy defined noncirrhotic MASH and moderate to advanced fibrosis, classified as F2 or F3.
• SYNCHRONY Real World is studying people with noninvasively diagnosed MASH or MASLD across a broader range of fibrosis stages.
• SYNCHRONY Outcomes is studying people with MASH cirrhosis.

These studies are intended to provide more information about the safety and effectiveness of efruxifermin in different groups of people with MASH.

What Do We Still Not Know About Efruxifermin?

This is where it is important to separate research findings from established treatment information.

The Phase 3 programme is still ongoing, so the full picture of long term safety and effectiveness is not yet available. Earlier trials can provide useful evidence, but they cannot guarantee that larger or longer studies will produce the same results.

Researchers are still studying questions such as:

• How effective efruxifermin is across different stages of MASH.
• How its effects hold up over longer periods.
• Which people may respond best.
• What side effects may occur with longer term treatment.
• How its benefits and risks compare with other treatment options.
• Whether future regulatory applications will contain enough evidence for an authorisation.

Until these questions are answered, efruxifermin remains an investigational medicine.

Is Efruxifermin Available in the UK?

What is its current regulatory status?

Efruxifermin is not currently licensed by the MHRA for routine clinical use.

The MHRA's records identify efruxifermin in connection with research into MASH, while the current Phase 3 programme remains ongoing.

So, if you see a website offering efruxifermin as a weight loss medicine for purchase or routine prescription, it should not be confused with an MHRA authorised medicine.

How can someone take part in research?

People who may be interested in participating in research need to go through the relevant clinical trial process.

Eligibility depends on the individual study. This can include factors such as the condition being studied, age, previous treatment, liver health and other medical criteria.

Clinical trials also involve informed consent and monitoring by the research team. Taking part in a trial is therefore very different from ordering an investigational medicine online.

How Is Efruxifermin Different From Weight Management Medicines Available Today?

The biggest difference is regulatory status and what each medicine has been authorised to treat.

Licensed medicines have been assessed by the relevant regulator for specific uses and can be prescribed when a person meets the appropriate clinical criteria. The MHRA currently lists licensed GLP 1 medicines including semaglutide, tirzepatide and liraglutide for specific uses.

Efruxifermin has not reached that stage. Its current development is focused on MASH, and its Phase 3 studies are still ongoing.

That distinction is especially important if you are searching for a medicine that you can access now. An investigational medicine should not be treated as an alternative to a licensed treatment simply because early research has produced interesting results.

Could Efruxifermin Eventually Be Used for Weight Management?

It is too early to say.

Research into FGF21 includes effects on metabolism, and body weight has been measured in some efruxifermin studies. However, future use depends on the evidence generated in clinical trials and on regulatory decisions.

A medicine cannot be described as a licensed weight management treatment until it has received authorisation for that use.

For now, efruxifermin should be understood as an investigational treatment being studied primarily for MASH.

Can Efruxifermin Be Combined With a GLP 1 Medicine?

This has been studied in clinical research.

A Phase 2 study evaluated efruxifermin alongside a GLP 1 receptor agonist in people with MASH and type 2 diabetes. The study reported changes in liver fat and other measures, but this combination remains investigational.

It should not be interpreted as advice to combine medicines. Someone should only use medicines together when that combination has been recommended and monitored by an appropriate healthcare professional.

Medical Disclaimer

This article is for general information only and does not replace individual medical advice.

Efruxifermin is an investigational medicine and is not currently licensed for routine use in the UK. It is being studied primarily for MASH in ongoing clinical trials. Research findings can change as further evidence becomes available, and early trial results do not guarantee future approval or a particular treatment outcome.

If you are concerned about your weight, liver health or a condition such as MASH, speak to a GP or another qualified healthcare professional about your individual circumstances.

Do not buy or use an investigational medicine based on claims made by an online seller or social media account.