What is Amgens drug MariTide?

Obesity is a global health crisis that continues to plague populations worldwide, with staggering statistics indicating that over 70% of adults in the United States are either overweight or obese. Despite the scale of this epidemic, effective treatment options have been limited, leaving millions struggling to manage their weight and associated health complications. However, the tide may be turning as Amgen, a leading biotech company, presents a promising new candidate in the fight against obesity – MariTide, also known as maridebart cafraglutide.

MariTide is a first-of-its-kind bispecific molecule that harnesses the power of two key metabolic pathways to drive significant weight loss. By simultaneously activating the glucagon-like peptide-1 (GLP-1) receptor and antagonizing the glucose-dependent insulinotropic polypeptide (GIPR), MariTide aims to revolutionize the treatment of obesity.

Let’s delve into the science behind MariTide, explore the promising results from Amgen’s clinical trials, and uncover the potential implications of this groundbreaking therapy for millions of individuals grappling with the challenges of obesity.

Understanding the obesity epidemic

Obesity is a complex condition that has reached pandemic proportions globally. According to the World Health Organization (WHO), the worldwide prevalence of obesity has tripled over the past four decades, with nearly 40% of adults classed as overweight and 13% considered obese.

The consequences of this epidemic are far-reaching, with obesity linked to a host of serious medical complications, including type 2 diabetes, cardiovascular disease, certain types of cancer, and even mental health issues. The burden on healthcare systems worldwide is staggering, with estimates suggesting that obesity-related costs account for up to 3% of a country’s total healthcare expenditure.

Despite the widespread recognition of obesity as a chronic disease, the development of effective treatment options has been challenging. Traditional approaches, such as lifestyle modifications and bariatric surgery have had limited success, with the vast majority of individuals struggling to achieve and maintain significant weight loss.

Introducing MariTide: A novel bispecific molecule

Amgen’s drug MariTide represents a groundbreaking approach to obesity treatment, harnessing the power of two key metabolic pathways to drive weight loss. The molecule is designed to simultaneously activate the GLP-1 receptor and antagonize the GIPR, a unique combination that has shown promise in preclinical and early-stage clinical studies.

GLP-1 is a hormone that plays a crucial role in regulating blood sugar levels and appetite. By activating the GLP-1 receptor, MariTide can enhance insulin secretion, slow gastric emptying, and promote feelings of fullness, leading to reduced calorie intake and subsequent weight loss. On the other hand, GIPR antagonism has been identified as a complementary strategy, as it can further enhance the weight-lowering effects by reducing the body’s ability to store excess calories as fat.

The dual action of these two mechanisms is what sets MariTide apart from other obesity treatments currently on the market or in development. By targeting these pathways simultaneously, the molecule aims to deliver a more potent and durable weight loss response, potentially offering a more effective solution for individuals struggling with obesity.

Amgen’s clinical trial findings

Amgen has carried out research to evaluate the safety and efficacy of MariTide, with promising results emerging from their Phase 1 clinical trials. The study published in the journal, Nature Metabolism, enrolled individuals with obesity, but without diabetes and showed significant weight loss outcomes with MariTide.

In the multiple ascending doses (MAD) groups, participants taking MariTide experienced mean per cent changes in body weight ranging from 7.2% at the lowest dose (140 mg administered every four weeks) to 14.5% at the highest dose (420 mg every four weeks), by day 85 of the study. Importantly, the weight loss observed was maintained well beyond the treatment period, highlighting the potential for long-term effects.

The safety profile of MariTide was also encouraging, with the majority of side effects being mild and short lived. The most common were gastrointestinal-related, such as nausea and vomiting, which typically resolved within 48 hours.

These promising Phase 1 results paved the way for Amgen to initiate a Phase 2 dose-ranging study in early 2023, with the results expected in late 2024.

The potential impact of MariTide

The successful development and approval of MariTide could have a great impact on the weight loss drug market.

One of the key advantages of MariTide lies in its dual mechanism of action. By simultaneously targeting the GLP-1 and GIPR pathways, this therapy has the potential to address the complex nature of obesity. This approach could lead to more substantial and sustainable weight loss results, potentially improving overall health and quality of life for individuals struggling with obesity.

A favorable safety profile observed in the Phase 1 trials suggests that MariTide may offer a well-tolerated treatment option, which could enhance patient compliance and long-term success. The ability to maintain weight loss beyond the treatment period is also a significant advantage, as it could help individuals achieve lasting results and reduce the risk of weight regain, a common challenge with many obesity drugs.

If approved, MariTide could potentially expand the treatment landscape for obesity, providing a much-needed alternative for the millions of individuals who have been unable to achieve their weight loss through traditional methods.

The obesity treatment landscape

MariTide is welcomed by healthcare providers and patients alike who continue to struggle with the limitations of existing therapies.

Traditional approaches, such as lifestyle changes and bariatric surgery often fail in delivering sustained weight loss. Pharmacological interventions, while offering more targeted solutions, have historically been let down by modest efficacy, safety concerns, or limited long-term results.

The discovery of GLP-1 receptor agonists, such as Novo Nordisk’s Wegovy (semaglutide) has been a significant improvement in the field, showing the potential of targeting the GLP-1 pathway to increase weight loss. Eli Lilly’s Zepbound (tirzepatide) injection combines the effects of two hormones, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP), to regulate blood sugar levels and promote weight loss. However, even these therapies have room for improvement, as some individuals may not achieve their desired weight loss goals, or may experience challenges with long-term maintenance.

Conclusion

MariTide’s unique dual approach, targeting both the GLP-1 and GIPR pathways, has the potential to address limitations and provide a better solution for obesity management. By using the synergistic effects of these two key metabolic pathways, the therapy aims to deliver more potent and sustained weight loss results for individuals struggling with this chronic condition.

Sources

• AMGEN PRESENTS NEW AMG 133 PHASE 1 CLINICAL DATA AT WCIRDC 2022 – Amgen