Evolocumab

iStock, Kwangmoozaa Amgen has launched a late-stage program to test the feasibility of switching patients from weekly GLP-1 injections to its own investigational obesity asset MariTide, which could open up monthly or more infrequent dosing schedules. In the lucrative and increasingly competitive obesity arena, Amgen isn’t looking to play third fiddle to Eli Lilly and Novo Nordisk. Instead, the California–based pharma is looking to chart a new paradigm with its weight-loss candidate MariTide, providing patients with not just efficacy but also convenience. “I think we are going to be the best monthly or less frequently dosed agent [in obesity],” Murdo Gordon, executive vice president of Amgen’s global commercial operations, told investors during the company’s first quarter earnings call Thursday afternoon. To build the case for MariTide as a top monthly weight-loss option, Amgen launched the Phase 3 MARITIME-Switch study in the first quarter, focusing on patients that are already on weekly GLP-1 treatment, according to a company presentation . “In other words, we will evaluate switching from medicines which are injected 52 times a year to one which can be injected as few as four or six times a year,” CEO Robert Bradway explained on the call. Amgen is also running late-stage programs for MariTide in type 2 diabetes, heart failure and obstructive sleep apnea. These studies, according to Gordon, will position MariTide as an alternative obesity treatment for patients who want to try something new. “Whether they are de novo patients who have yet to attempt a weight loss treatment and they will be new to MariTide, or whether they are on another therapy and they are not achieving the results they like, or they are not enjoying the frequency of injections, or they are having side effects and they want to try another treatment,” he said on the call. “We will, across the business, across the company, be ready to go into that market and compete with all of the other companies that are already there,” Gordon said. MariTide is a bispecific antibody-peptide that works by simultaneously activating the GLP-1 pathway while also disrupting GIP. Amgen has previously claimed that this mechanism not only triggers weight loss but also helps patients keep the pounds off after stopping treatment. Unlike the currently approved treatments, which are dosed weekly for injectables or taken daily for pills, MariTide is, at its most frequent schedule, a monthly injection. Obesity Beyond MariTide: Amgen Makes Portfolio Play Amid Scrutiny of Obesity Prospect Suddenly one obesity asset has come to define Amgen but executives see a fuller portfolio that will bring the big biotech into the future. September 10, 2025 · 5 min read · Nick Paul Taylor Read more In November 2024, Amgen unwrapped Phase 2 data for MariTide, touting an up to 20% reduction in body weight at 52 weeks, an effect that fell on the lower end of what investors had been expecting. Analysts were underwhelmed. Still, the pharma remains confident in the asset, with Gordon on Thursday playing up the “paradigm-changing opportunity” that MariTide presents in the obesity market. Amgen management on the call also described high-level results from a Phase 1 study evaluating a three-step dose escalation of the drug, according to a Friday note from William Blair. “We are encouraged by the additional tidbits on the call on MariTide,” the analysts said, “including the improved tolerability with three-step dose escalation and the initiation of a new switch study, which we believe would support uptake.” Amgen clocked $8.6 billion in first quarter revenues, up 6% year-on-year. Based on first quarter sales, the pharma could have 17 blockbuster products this year and annual sales hitting at least $1 billion, according to a company release on Thursday . These include the lipid-lowering drug Repatha, which emerged as Amgen’s best-selling product at $876 million worldwide—a 34% year-on-year growth. Other top-performing drugs included the osteoporosis drugs Evenity and Prolia, which brought in $562 million and $727 million, respectively.

A new breakthrough could change how high cholesterol is treated, offering a powerful alternative to traditional drugs. Researchers have developed tiny DNA-based molecules that shut down PCSK9—a key protein that keeps “bad” LDL cholesterol circulating in the blood. By blocking this protein, cells can absorb more cholesterol instead of letting it build up in arteries, dramatically lowering levels linked to heart disease.High levels of cholesterol in the bloodstream can lead to hypercholesterolemia, a condition that damages arteries and raises the risk of heart disease. Now, researchers from the University of Barcelona and the University of Oregon have developed a promising new approach to control cholesterol levels, offering a potential new way to combat atherosclerosis, which occurs when fatty plaques build up in artery walls. The research team focused on PCSK9, a protein that plays a central role in regulating levels of low-density lipoprotein cholesterol (LDL-C), often called "bad" cholesterol. They designed a method to block the production of this protein using specialized DNA-based molecules known as polypurine hairpins (PPRH). By suppressing PCSK9, the treatment helps cells absorb more cholesterol, reducing the amount circulating in the blood and limiting buildup in the arteries. Importantly, this approach may avoid the side effects commonly linked to statin medications. The findings were published in the journal Biochemical Pharmacology. The study was led by Carles J. Ciudad and Verònica Noé from the University of Barcelona's Faculty of Pharmacy and Food Sciences and the Institute of Nanoscience and Nanotechnology (IN2UB), working with Nathalie Pamir at the University of Oregon in Portland (United States). Funding came from the Spanish Ministry of Science, Innovation and Universities (MICINN) and the National Institutes of Health (NIH) in the United States. How Polypurine Hairpins Block a Key Cholesterol Protein PCSK9 (protein convertase subtilisin/kexin type 9) has become an important target in recent years for therapies aimed at lowering cholesterol and reducing cardiovascular risk. The protein works by attaching to LDL receptors on cells, limiting their ability to remove cholesterol from the bloodstream. When PCSK9 levels are high, fewer receptors are available, causing LDL cholesterol to accumulate in the blood. Polypurine hairpins (PPRHs) offer a way to interrupt this process at the genetic level. These molecules are short strands of DNA that can bind very precisely to specific DNA or RNA sequences and block gene activity. In this case, PPRHs prevent the PCSK9 gene from being transcribed, which leads to an increase in LDLR receptor levels and improves the body's ability to pull cholesterol out of circulation. As a result, overall cholesterol levels drop and the risk of plaque formation is reduced. The study describes for the first time how two specific PPRHs, called HpE9 and HpE12, reduce both PCSK9 RNA and protein while boosting LDL receptor levels. "Specifically, one of the arms of each chain of the HpE9 and HpE12 polypurines binds specifically to polypyrimidine sequences of exons 9 and 12 of PCSK9, respectively, via Watson-Crick bonds," notes Professor Carles J. Ciudad, from the Department of Biochemistry and Physiology. This interaction blocks gene transcription and interferes with the activity of RNA polymerase or transcription factors. Strong Results in Cells and Animal Models The researchers tested the therapy in laboratory-grown liver cells and in transgenic mice that carry the human PCSK9 gene. The results were significant. "The results show that both HpE9 and HpE12 are highly effective in HepG2 cells. HpE12 decreases PCSK9 RNA levels by 74% and protein levels by 87%. In the case of transgenic mice, a single injection of HpE12 reduces plasma PCSK9 levels by 50% and cholesterol levels by 47% on the third day," says Professor Verònica Noé. A Potential Alternative to Statins Since PCSK9 has become a major target for cholesterol-lowering therapies, several approaches have been developed to block its effects. These include gene-silencing technologies such as siRNAs, antisense oligonucleotides, and CRISPR-based methods. Existing treatments like Inclisiran, an siRNA therapy, and monoclonal antibodies such as evolocumab and alirocumab are already in use. However, PPRHs may offer unique advantages. "PPRHs, especially HpE12, are therapeutic oligonucleotides with many advantages, including low cost of synthesis, stability and lack of immunogenicity. In addition, such a PPRH-based approach against PCSK9 would not lead to side effects such as the myopathies associated with statin therapy," the experts conclude. If confirmed in further studies, this new strategy could provide a safer and more targeted way to lower cholesterol and reduce the risk of heart disease.