What are the side effects of MariTide?

Amgen’s obesity drug, MariTide, marks a significant advance in the fight against obesity. This innovative treatment, designed as a once-monthly injection, targets GLP-1 and GIP receptor agonists to help individuals achieve and maintain weight loss. It’s unique mechanism works differently than Novo Nordisk’s Wegovy (semaglutide) or Eli Lilly’s Zepbound (tirzepatide).

As MariTide enters Phase 3 testing, the focus is on its potential to manage obesity and obesity-related conditions, including type 2 diabetes. The following sections will delve into the mechanism of action of this promising drug, and explore the reported side effects from clinical trials.

Understanding MariTide and its mechanism

Amgen’s drug MariTide, also called maridebart cafraglutide represents a novel approach as a weight loss drug and has shown potential in diabetes management. How does it work? Let’s take a look at its mechanism.

Mechanism of action

MariTide functions uniquely by combining two powerful mechanisms: Blocking the GIP receptor and mimicking the gut hormone GLP-1. This dual action not only regulates appetite but also influences body weight and fat mass reduction.

• GIP receptor blockade: MariTide inhibits the action of the GIP (Gastric Inhibitory Polypeptide) receptor, which is known to play a role in energy balance and fat storage
• GLP-1 receptor activation: Simultaneously, the drug mimics GLP-1 (Glucagon-like Peptide-1), a hormone involved in insulin secretion and appetite regulation. This hormone interacts with the hypothalamus and other organs to reduce food intake

Drug design and structure

MariTide is an advanced bispecific molecule, meaning it targets two different pathways. It has been designed by joining a fully human monoclonal anti-human GIPR antagonist antibody to two GLP-1 analogue agonist peptides. This structure allows MariTide to remain in the body longer compared to other weekly weight-loss injections.

• Longevity in the body: The antibody component of MariTide provides it with a longer half-life in the body, enhancing its effectiveness and reducing the frequency of administration
• Bispecific nature: The combination of anti-GIPR monoclonal antibody and GLP-1 receptor agonist in one molecule helps in achieving more significant weight loss than using either agent alone

Clinical development

MariTide is currently undergoing Phase 2 clinical trials, with Amgen focusing on demonstrating its efficacy with a once-monthly injection regimen. Early trials have shown promising results in weight reduction.

• Phase 1 results: In initial human trials, participants showed substantial weight loss, maintaining it for up to five months post-treatment. The highest dose resulted in an average weight loss of 8.2% on Day 92
• Safety profile: While generally well tolerated, the most common side effects noted were gastrointestinal, such as mild nausea and vomiting

Reported side effects from clinical trials

Gastrointestinal issues

Most participants in the clinical trials experienced gastrointestinal symptoms, primarily nausea and vomiting. These side effects were particularly prevalent in those receiving higher doses of MariTide.

• Nausea and vomiting: This was the most frequently reported side effect across various study groups
• Withdrawal due to side effects: In the group receiving the highest dose, four out of eight patients discontinued the study due to these mild gastrointestinal issues

Pancreatic concerns

A notable concern that appeared during the trials was the increase of pancreatic enzymes, which can show pancreatic stress or damage.

• Elevated pancreatic enzymes: Instances of elevated enzymes were observed in one patient in the single-dose group and another in the multiple-dose group, both receiving a 140-mg dose
• Resolution of symptoms: Despite the increase, these enzyme levels returned to normal without the need for clinical intervention, suggesting that the effect might be short lived
• Comparison with other GLP-1 medications

The side effects noted in the MariTide trials were similar to those observed with other medications in the GLP-1 drugs, with gastrointestinal disturbances being the most common.

Weight loss and retention

Patients in the trials not only achieved significant weight loss, but also maintained it for an extended period post-treatment, highlighting MariTide’s potential for long-term obesity management.

• Immediate weight loss: Patients lost up to 14.5% of their body weight within 12 weeks when administered monthly injections
• Long-term effectiveness: Some participants maintained their reduced weight for up to 150 days after discontinuing the drug

Long-term efficacy and safety studies

• Extended duration studies: Amgen is conducting parts of its Phase 2 trial to explore the weight loss sustainability beyond 52 weeks with MariTide. This will provide clearer results on the long-term effectiveness of the drug
• Phase 3 testing: The upcoming Phase 3 trials will further research MariTide’s efficacy in treating obesity, obesity-related conditions, and type 2 diabetes. This phase will be crucial for understanding the long-term safety and potential side effects of the drug

Conclusion

It’s clear that the unique dual mechanism of MariTide shows promise in the treatment of obesity. The encouraging results from early clinical trials, including significant weight loss, give healthcare providers and patients another potential option to aid weight loss. Nevertheless, as we navigate through the side effects, ranging from gastrointestinal issues to concerns about pancreatic enzymes, it is important to be cautious until research becomes clear.

As MariTide advances through the clinical pipeline the significance for patients dealing with obesity is profound. The expected introduction of MariTide to the market around 2028 opens the way for a novel therapeutic option in obesity management.

Sources

• AMGEN PRESENTS NEW AMG 133 PHASE 1 CLINICAL DATA AT WCIRDC 2022 – Amgen
• A GIPR antagonist conjugated to GLP-1 analogues promotes weight loss with improved metabolic parameters in preclinical and phase 1 settings | Nature Metabolism