What Is Petrelintide?

Danish biotech Zealand Pharma is working on the next generation of weight loss treatment. In a recent press release this month, Denmark based Zealand Pharma announced they were entering a joint collaboration and license agreement with Roche Pharmaceuticals to develop and bring to market petrelintide as a future weight management drug.

Early stage clinical trials of petrelintide which mimics the hormone amylin is showing promising weight reduction with results comparable to GLP-1 receptor agonist, such as Novo Nordisk’s Wegovy (semaglutide) and Eli Lilly’s Zepbound, but potentially offering a better patients experience. Lets take a deeper look into this potential new obesity drug.

? What is the mechanism of action of amylin?

Petrelintide belongs to a class of drugs that bind to and activate the amylin receptor called long-acting amylin analogues. This once-weekly subcutaneous administration drug is a peptide designed to be a long-acting version of amylin, a hormone in the body that plays a role in regulating blood sugar and appetite. Activating the amylin receptor is intended to restore sensitivity to leptin, a hormone that signals satiety. Rather than suppressing appetite, Zealand says its drug helps patients feel full faster.

? Why is amylin important?

Amylin is a pancreatic peptide hormone that is released by the pancreas at the same time as insulin. Amylin was first identified in 1987. Petrelintide also known scientifically as ZP8396 and as a 36-amino-acid acylated peptide is based on the peptide sequence of human amylin.

Amylin can be described as a sidekick to insulin. It starts working during and after meals. The hormone instructs the liver to release less glucagon (a stored sugar), which helps prevent blood glucose spikes. It also slows gastrointestinal emptying, helping to curb the appetite.

So what happens when your body isn’t making enough amylin? Bigger glucose spikes and increased hunger, driving weight gain.

? What are the potential benefits of using petrelintide for weight management?

Zealand and Roche hope to offer weight loss results comparable to GLP-1 drugs while offering better tolerability. Gastrointestinal side effects are common with GLP-1 drugs, leading many patients to stop treatment. The weight loss from these drugs includes muscle reduction as well as fat reduction which affects the patient experience. Targeting amylin is hoped to preserve muscle.

? What are the results of the petrelintide clinical trial?

In a 16-week, Phase 1, multiple ascending dose (MAD) clinical trial, Zealand reported that petrelintide led to an average 8.3% loss in body weight for the highest of three doses tested, versus a 1.7% average weight loss for the placebo group. All gastrointestinal adverse events were mild, except for two moderate nausea and vomiting events reported in one participant who discontinued treatment.

The MAD trial showed no serious or severe adverse events (AEs) and no withdrawals from treatment. The most frequent related adverse events were decreased appetite, early satiety, food aversion and nausea. These all were mild, transient and most had an onset within 2 days of the first dose.

Nausea occurred in three subjects treated with petrelintide, with one also reporting vomiting, no other subjects reported vomiting. There were no reports of injection site reactions and no subjects developed anti drug antibodies.

These results were presented at the Obesity Society Annual Meeting (ObesityWeek) in 2024.

? Conclusion

Amylin analog petrelintide is emerging as an important therapeutic option for chronic weight management. The drug is unlikely to be released or face regulatory approval for several years, as Zealand noted testing for petrelintide is still in its early clinical development. Obesity is one of the greatest healthcare challenges faced by society, but there is new hope with petrelintide ahead.

Sources

• Scientific publications – Pipeline – Zealand Pharma
• PowerPoint Presentation
• zp8396-phase1-mad-part-1-obesityweek-2023.pdf