Will Hanmi be able to develop its own Saxenda for Koreans?

Hanmi Pharm starts development of its GLP-1 receptor agonist ‘efpeglenatide’ for the obesity indication

Reduced 3.34kg on average in a global Phase III trial as a diabetes drug. domestic. trial design as an obesity drug will be key

Hanmi Pharm has decided to change the development direction for its GLP-1 class drug ‘efpeglenatide.’ Instead of developing it as a diabetes treatment as before, the company plans to develop the drug as an obesity treatment.

 

The industry’s attention was focused on the Global Phase III trial that Sanofi and Hanmi Pharm had conducted with efpeglenatide as a diabetes treatment.

 

The results of the trial, 'AMPLITUDE-M,’ had indirectly confirmed the weight loss effect of efpeglenatide.

 

In the trial, the weight of patients in the U.S.

 

and Europe with diabetes who received 4mg efpeglenatide fell by 3.34kg on average.

 

However, it would be difficult to rashly assume the results as the race or body mass index (BMI) of the participants may differ greatly if a new clinical trial is conducted in Korea for the drug as an obesity treatment.

 

’Just like Saxenda’...

 

Hanmi Pharm changes development direction from antidiabetic→obesity drug Hanmi Pharm announced on the 31st of last month that it will develop efpeglenatide as an obesity treatment.

 

On the 28th of last month, the company submitted an Investigational New Drug (IND) application to the Ministry of Food and Drug Safety for efpeglenatide to conduct a Phase III clinical trial with efpeglenatide as an obesity treatment.

 

The company plans to change the development direction from diabetes treatment to obesity treatment.

 

It is not completely giving up on the development of diabetes treatment, but a company official explained that the company plans to focus its capabilities on developing it as an obesity treatment in the near future.

 

Efpeglenatide is classified as a GLP-1 analogue.

 

GLP-1 analogues have a similar structure to human GLP-1 hormones.

 

This hormone is secreted in response to meal ingestion and enhances insulin secretion by acting on the pancreatic beta-cells and reducing glucagon secretion to bring a glucose-lowering effect.

 

It also acts on the brain to reduce appetite and delay the passage of food to enhance satiety.

 

This is why the drug can work as a diabetes treatment while showing a weight loss effect.

 

Global pharmaceutical companies have long been investigating this unique mechanism of action.

 

Novo Nordisk opened the door to this field with the release of ‘Saxenda.’ Novo Nordisk transformed its diabetes drug, the GLP-1 analogue Victoza, into the obesity treatment Saxenda by changing its dose.

 

Pic of Novo Nordisk

After Saxenda became a global sensation, companies have continued to develop follow-up drugs.

 

Novo Nordisk has released ‘Wegovy,’ a long-acting GLP-1 analog, as its next-generation obesity treatment.

 

Eli Lilly, which owns 'Trulicity' as a GLP-1 analog type diabetes treatment, has developed another next-generation drug, GLP-1/GIP dual agonist ‘Mounjaro.’ Both Wegovy and Mounjaro were received with great attention, to the extent that large shortages of both have occurred in the US since their release.

 

In the case of Mounjaro, the US Food and Drug Administration approved the drug as a diabetes treatment, but the drug is being prescribed to obesity patients off-label.

 

Hanmi Pharm is also on a similar track.

 

Rather than launching efpeglenatide as a latecomer to the diabetes treatment market, which is already saturated with various classes of drugs in the market, the company is known to be seeking to jump into the budding obesity treatment market.

 

Global Phase III trial on efpeglenatide as a diabetes drug showed ‘3.34kg weight reduction' The industry has been paying attention to the results of the global Phase III trial that Hanmi Pharm has conducted with efpeglenatide as a diabetes treatment to indirectly check on the weight loss effect of efpeglenatide.

 

The company had signed a license-out agreement with Sanofi in 2015.

 

At the time, Sanofi led 5 global Phase III trials were conducted on efpeglenatide.

 

However, Sanofi returned all the rights to Hanmi in June 2020.

 

Since then, the company received all clinical data from the 5 trials and has been seeking new commercialization opportunities.

 

One result to note among the 5 trials is one that compared 3 different doses of efpeglenatide with placebo.

 

The trial set the primary efficacy endpoint of the trial as the change in glycated hemoglobin (HbA1c).

 

At the time, Hanmi Pharm had also evaluated the weight change of the patients at 30 weeks and 56 weeks as one of the secondary endpoints of the trial.

 

The trial was conducted on 406 patients in the U.S.

 

and Europe.

 

The mean BMI of the trial participants was 34.2㎏/㎡.

 

The mean BMI by administered doses were: ▲placebo(102 patients) 34.8㎏/㎡ ▲ efpeglenatide 2㎎ (100 patients) 34.4㎏/㎡ ▲ efpeglenatide 4㎎ (101 patients) 33.8㎏/㎡ ▲ efpeglenatide 6㎎ (103 patients) 33.8㎏/㎡.

 

At 30 weeks of administration, the weight loss effect was greatest in the 4mg group.

 

The 102 people in the placebo group lost an average of 1.35 kg.

 

The group that was administered efpeglenatide 2 mg lost an average of 1.01 kg.

 

The mean weight loss was 3.34kg in the 4mg group and 3.19kg in the 6mg group.

 

At 56 weeks of administration, the placebo group lost an average of 1.26kg.

 

The group that was administered efpeglenatide 2 mg lost an average of 0.95 kg.

 

The mean weight loss was 3.24kg in the 4mg group and 1.82kg in the 6mg group.

 

At both the 30th and the 56th week, the weight loss effect tended to be prominent in the 4mg group.

 

Weight loss effect of efpeglenatide as a diabetes treatment in a global Phase III trial (Data: clinicaltrials.gov)

There was no significant difference in the incidence of serious adverse events, including cardiovascular events, between the placebo and control groups.

 

’Development of an obesity treatment tailored to Koreans’...

 

raises interest in the design of the clinical trial Hanmi Pharm had announced that it would develop efpeglenatide into an ‘obesity treatment customized for Koreans,’ It added that it would develop a drug optimized for the BMI of 25 kg/m2, which is the obesity standard for Koreans.

 

Although the specifics of its clinical design have not been disclosed, it is speculated that the trial will recruit and enroll people with a BMI of 25 kg/m2 or higher.

 

This is expected to be somewhat different from the global diabetes Phase III clinical trial that had been conducted on efpeglenatide.

 

In the case of the global clinical Phase III trial, the average BMI was 34.2 kg/m2.

 

In particular, only 112 (27.6%) of the 406 people who participated in the trial had a BMI of less than 30 kg/m2.

 

Another difference is that the previous global Phase III trial for efpeglenatide as a diabetes treatment was conducted mainly on white, black, and Hispanic subjects.

 

Of the total 406 participants, only 5 (1.2%) were Asians.

 

This means that different results may be derived even though the same drug was used due to different demographics.

 

Therefore, industry officials unanimously say that the design of the domestic Phase III clinical trial will determine the success or failure of Hanmi’s development of efpeglenatide as an obesity drug for Koreans.

 

An industry official said, “Although it is the same drug, the target is different and the composition of the clinical participants will also be very different from the previous clinical trials.

 

In the case of Wegovy, a study had shown that the drug demonstrated weight loss in East Asians.

 

In the case of efpeglenatide, the results may also differ depending on the clinical design.” Hanmi is also clearly aware of this.

 

An official from Hanmi Pharm said, "Global pharmaceutical companies that have developed GLP-1-based obesity treatments are competitively announcing the rate of weight loss, but the reported figures are only beneficial to highly obese patients in the West.

 

We will develop an obesity drug customized for Koreans that takes into consideration the body shape and weight of Koreans.”