MariTide Demonstrated up to ~20% Average Weight Loss at 52 Weeks Without a Weight Loss Plateau in People Living With Obesity or Overweight
MariTide is the First Obesity Treatment With Monthly or Less Frequent Dosing to Demonstrate Safe and Effective Weight Loss in a Phase 2 Study
In People With Type 2 Diabetes Living With Obesity or Overweight MariTide Demonstrated up to ~17% Average Weight Loss Without a Weight Loss Plateau and Lowered Average HbA1c by up to 2.2 Percentage Points at 52 Weeks
MariTide Delivered Substantial Improvements Across Cardiometabolic Parameters
Amgen Announces “MARITIME,” a Phase 3 Clinical Development Program in Obesity and Obesity-Related Conditions
THOUSAND OAKS, CA, USA I November 26, 2024 I Amgen (NASDAQ:AMGN) today announced positive data at 52 weeks in a double-blind, dose-ranging Phase 2 study with MariTide (maridebart cafraglutide, formerly AMG 133), an investigational antibody peptide conjugate subcutaneously administered monthly or less frequently. In people living with obesity or overweight without Type 2 diabetes, MariTide demonstrated up to ~20% average weight loss at week 52 without a weight loss plateau, indicating the potential for further weight loss beyond 52 weeks.1 The study also showed people living with obesity or overweight and Type 2 diabetes, who typically lose less weight on GLP-1 therapies, achieved up to ~17% average weight loss, also without a weight loss plateau, and lowered their average hemoglobin A1C (HbA1c) by up to 2.2 percentage points at week 52.1 In summary, in both study populations, a weight loss plateau was not observed, again indicating the potential for further weight loss beyond 52 weeks.
MariTide also demonstrated robust and clinically meaningful improvements in cardiometabolic parameters, including blood pressure, triglycerides and high-sensitivity C-reactive protein (hs-CRP) across doses. There were no significant increases in free fatty acids.
There was no association between the administration of MariTide and bone mineral density changes.
The most common adverse events (AEs) in the Phase 2 study were gastrointestinal (GI) related, including nausea, vomiting and constipation. Nausea and vomiting were predominately mild, transient and primarily associated with the first dose. The incidence of nausea and vomiting was substantially reduced with dose escalation. In the dose escalation arms, for those with symptoms, nausea and vomiting were episodic; generally resolving within a median window of six days for nausea and one to two days for vomiting. The discontinuation rate in the dose escalation arms due to any AE was ~11% and less than 8% for GI-related events. No additional safety signals were identified. In a separate ongoing Phase 1 pharmacokinetic study, additional dosing regimens have been evaluated in a planned preliminary analysis.
“We are very excited by MariTide’s differentiated profile, with clinically meaningful attributes of substantial and progressive weight loss, monthly or less frequent dosing, significant improvements in cardiometabolic parameters and strong reduction of HbA1C,” said Jay Bradner, M.D., executive vice president of Research and Development and chief scientific officer at Amgen. “These results provide us confidence to initiate MARITIME, a Phase 3 program across obesity and a number of related conditions, providing a unique potential new treatment option for patients.”
Data from this Phase 2 study will be presented at a future medical congress and submitted for publication.
The ongoing Part 2 of the Phase 2 study is investigating MariTide beyond 52 weeks to evaluate further weight loss with continued treatment, weight maintenance through less frequent or lower dosing and durability of weight loss after discontinuation of MariTide. More than 90% of eligible patients chose to continue to participate in Part 2 of the study.
MariTide is expected to be delivered as a single dose in a convenient, handheld, patient-friendly, autoinjector device with a monthly or less frequent single-injection administration. MariTide is produced in Amgen’s industry-leading manufacturing network.
Amgen is also advancing its obesity pipeline, which includes both oral and injectable approaches, composed of both incretin and non-incretin mechanisms.
The company announced that it is hosting a webcasted call for the investment community at 5 a.m. PT on Tuesday, Nov. 26, 2024, to provide a MariTide update. The webcast, as with other selected presentations regarding developments in Amgen’s business given by management at certain investor and medical conferences, can be found on Amgen’s website, www.amgen.com, under Investors.
About Obesity
Obesity is a complex biological disease that increases the risk of many other serious diseases and conditions, including Type 2 diabetes, heart failure, kidney disease, sleep apnea, atherosclerotic cardiovascular disease and metabolic dysfunction-associated steatohepatitis. The worldwide prevalence of obesity more than doubled between 1990 and 2022.2 In the U.S., more than two in five adults (42.5%) are living with obesity.3 In 2022, 890 million adults (18 years and older) globally were living with obesity, and 2.5 billion adults were living with overweight.2
Obesity is linked to a marked reduction in quality of life and an array of serious medical complications and conditions.4,5 Despite the breadth of the disease, the formal recognition of obesity as a chronic disease by the American Medical Association (2013) and the European Health Commission (2021), and medical guidelines recommending pharmacologic treatment in appropriate individuals, only 1%-3% of eligible adults in the U.S. are prescribed medication for chronic weight management.6-8
About MariTide
MariTide is a bispecific glucagon-like peptide 1 (GLP-1) receptor agonist and glucose-dependent insulinotropic polypeptide receptor (GIPR) antagonist being investigated for the treatment of obesity and Type 2 diabetes mellitus. As a pioneering antibody-peptide conjugate molecule with a long half-life and dual mechanism of action, MariTide may allow for greater durability or reduce the likelihood of weight rebound after treatment stops. Pre-clinical studies have demonstrated that simultaneously activating GLP-1 and inhibiting GIP pathways had a stronger effect on weight loss than targeting either GLP-1 or GIP receptors alone. Amgen utilized its strong capabilities of human genetics to confirm the benefits of GIPR inhibition.
The clinical goal for people living with obesity or overweight is to achieve weight loss, and to maintain weight thereby improving health. Given the heterogeneity of obesity and the number of people impacted, a variety of approaches will be needed. In addition to MariTide, Amgen is also advancing an obesity pipeline, which includes both oral and injectable approaches, composed of both incretin and non-incretin mechanisms.
About the Phase 2 Study (NCT05669599)
The trial enrolled 592 adults included two Cohorts of people living with obesity or overweight. Cohort A enrolled participants without a diagnosis of Type 2 diabetes, Cohort B participants had Type 2 diabetes. In Part 1, participants in Cohort A (n=465), without Type 2 diabetes, were assigned to one of four monthly fixed dose arms (placebo, 140 mg, 280 mg, 420 mg) or an 8-week 420 mg dose arm. There were also two dose escalation arms with either 4-week or 12-week dose escalation periods to a target dose of 420 mg. Adults in Cohort B (n=127), with type 2 diabetes, were assigned to one of four monthly fixed dose arms (placebo, 140 mg, 280 mg and 420 mg). At the end of Part 1, participants who met eligibility criteria (at least 15% weight loss at week 52 and still taking investigational product) had the option to enter Part 2 of the study.
Part 2 of this Phase 2 study is investigating MariTide beyond 52 weeks. In Part 2, Cohorts from Part 1 were pooled, then re-randomized based on their Part 1 doses to receive either placebo or a fixed monthly dose of 70 mg, 140 mg, 420 mg or a 12-week 420 mg dose. The purpose of Part 2 is to evaluate further weight loss with continued treatment, durable weight loss after discontinuation of MariTide and weight maintenance through less frequent or lower dosing.
For more detailed information about the study, please visit https://clinicaltrials.gov/study/NCT05669599.
We will initiate “MARITIME,” a Phase 3 program in obesity and obesity-related conditions. For more information about participating in our clinical studies, please visit www.maritimestudy.com.
About Amgen
Amgen discovers, develops, manufactures and delivers innovative medicines to help millions of patients in their fight against some of the world’s toughest diseases. More than 40 years ago, Amgen helped to establish the biotechnology industry and remains on the cutting-edge of innovation, using technology and human genetic data to push beyond what’s known today. Amgen is advancing a broad and deep pipeline that builds on its existing portfolio of medicines to treat cancer, heart disease, osteoporosis, inflammatory diseases and rare diseases.
In 2024, Amgen was named one of the “World’s Most Innovative Companies” by Fast Company and one of “America’s Best Large Employers” by Forbes, among other external recognitions. Amgen is one of the 30 companies that comprise the Dow Jones Industrial Average®, and it is also part of the Nasdaq-100 Index®, which includes the largest and most innovative non-financial companies listed on the Nasdaq Stock Market based on market capitalization.
For more information, visit Amgen.com and follow Amgen on X, LinkedIn, Instagram, TikTok, YouTube and Threads.
References
1 The treatment-regimen estimand assessed effects regardless of treatment discontinuation in the intention-to-treat population.
2 World Health Organization. Obesity and overweight fact sheet. https://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight. Updated March 1, 2024. Accessed November 12, 2024.
3 Fryar, C.D., Carroll., M.D., Afful, J. (2020). Prevalence of overweight, obesity, and severe obesity among adults aged 20 and over: United States, 1960–1962 through 2017–2018. NCHS Health E-Stats. www.cdc.gov/nchs/data/hestat/obesity-adult-17-18/obesity-adult.htm.
4 Centers for Disease Control and Prevention. Consequences of Obesity. https://www.cdc.gov/obesity/basics/consequences.html. Accessed November 12, 2024.
5 Hecker J, Freijer K, Hiligsmann M, Evers SMAA. Burden of disease study of overweight and obesity; the societal impact in terms of cost-of-illness and health-related quality of life. BMC Public Health. 2022;22:46.
6 Samaranayake NR, Ong KL, Leung RY, Cheung BM. Management of obesity in the National Health and Nutrition Examination Survey (NHANES), 2007–2008. Ann Epidemiol. 2012;22(5):349–53.
7 Xia Y, Kelton CM, Guo JJ, Bian B, Heaton PC. Treatment of obesity: Pharmacotherapy trends in the United States from 1999 to 2010. Obesity (Silver Spring). 2015;23(8):1721–8.
8 Saxon DR, et al. Antiobesity Medication Use in 2.2 Million Adults Across Eight Large Health Care Organizations: 2009-2015. Obesity. 2019;27:1975-1981.
SOURCE: Amgen
