Retatrutide

Amgen said its experimental weight loss drug MariTide helped obese patients lose 20% of their weight after a year of treatment with the shot. And while it was touted as a win, the data immediately raised questions about the dose the company will take forward and how it stacks up with competitors. The company plans to start a Phase 3 program, and believes its manufacturing prowess can help it win part of the market share if approved. It also emphasized the monthly dosing for the drug, which is less frequent than approved treatments, and that patients appeared to keep losing weight through the end of the study — suggesting the weight loss effects could grow. This is one of the most anticipated drug readouts of the year — not just for Amgen, but for the biotech market at large. And they come as the Biden administration announced on Tuesday that it wants to have Medicare and Medicaid pay for the drugs — a move worth billions of dollars if the incoming Trump administration follows through. Investors viewed the data as a disappointment, sending the shares $AMGN down almost 12% in early trading. While the results were strong, they don’t appear meaningfully better than what Eli Lilly has reported with Zepbound. Two doses of Lilly’s drug have shown weight loss of 19.5% and 20.9% at 72 weeks. And there’s another high bar to clear after Lilly’s experimental candidate, retatrutide, showed weight loss of 24.2% at 48 weeks. Amgen tested three different doses of MariTide with multiple different dosing methods. And while it highlighted the 20% weight loss, that effect came from the second-highest dose (280 mg) of MariTide, while pooled data of the highest dose (420 mg) appeared to show some percentage points less of weight loss. But the company didn’t provide specific weight loss figures (or side effect rates) for the 420 mg dose arms of the trial. While research chief Jay Bradner said the efficacy data were “comparable” between them, there were questions about exactly why a lower dose appeared to perform better, and what the data look like for the regimen the company takes into Phase 3. Bradner advised analysts on a call after the news was announced to not “read anything into the appearance of the data for 280 versus 420,” citing the larger number of patients in the 420mg arms. There will also be questions about side effects, which Amgen said it was working to curb through changes in dosing. About 11% of patients dropped out of the trial group where Amgen was increasing the dose, and most of them came early on in the trial. Most of those dropouts (8% of patients) were for gastrointestinal side effects like vomiting, nausea and constipation. Amgen reported that 70% of patients in the escalation arms experienced nausea and 40% experienced vomiting. The company emphasized that it believed the side effect profile was manageable. “We have a competitive safety profile. Dose escalation for this medicine works,” Bradner told analysts. Susan Sweeney, head of Amgen’s obesity and related conditions unit, said on a media call that the nausea and vomiting rates “substantially decrease” over a year. Amgen is betting that patients and payers will flock to a less frequent dosing option that could give it an entry point into a market dominated by Novo and Lilly. Their weight loss treatments, Novo’s Wegovy and Lilly’s Zepbound, are administered once weekly, and in some patients come with side effects like nausea and vomiting, in addition to patchy insurance coverage. Amgen’s Phase 2 trial included nearly 600 patients across 11 arms, most of whom had obesity but not type 2 diabetes. The obesity-only patients were randomized to receive either placebo or one of three doses of MariTide every four weeks. Another arm received the highest dose, 420 mg, every eight weeks. Two additional arms tested different titration regimens to get up to 420 mg doses. “We think this is going to be a very attractive option in the marketplace,” Amgen CEO Bob Bradway said. MariTide uses a different mechanism of action than some other drugs. While other products activate the glucose-dependent insulinotropic polypeptide (GIP) receptor, MariTide blocks it. In an interview ahead of the data release, Bradner said that the decision originated out of deCODE genetics, Amgen’s gene-sleuthing subsidiary based in Iceland. “Our scientists discovered that mutations of the GIP receptor protect against obesity, and they protect against many of the obesity-related conditions,” he said. Peptides activating GLP-1 receptors were added to MariTide to “bolster its activity,” Bradner said. Lilly chief scientific officer Dan Skovronsky recently told analysts that he expected Amgen’s efficacy will be a result of the GLP-1 component of the molecule, rather than the GIP antagonism. Tirzepatide, Lilly’s blockbuster weight loss and diabetes treatment, activates both GIP and GLP-1. MariTide’s seemingly contradictory mechanism has been a point of debate among scientists in the field , as the data mark a seminal moment for the potential of GIP antagonism. There have also been concerns that blocking GIP could spur reductions in bone mineral density after a small tranche of Phase 1 data was uncovered earlier this month by analysts at Cantor Fitzgerald, though Amgen has tried to dispel that association. “We measure bone mineral density just like everybody else in our field with these medicines,” Bradner said. “But human genetics supports the idea that a medicine built this way might have no effect on bone mineral density.” In its announcement Tuesday, Amgen said that there had been “no association between the administration of MariTide and bone mineral density changes.” In the upcoming Phase 3 study, Amgen plans to study MariTide in additional obesity-related conditions, which could include sleep apnea, cardiovascular and heart disease, among others. Bradner said ahead of the readout that the Phase 3 program aims to “capture the greatest possible impact and generate the greatest possible value from the MariTide medicine.” Editor’s note: This story has been updated throughout with details from Amgen’s presentations to investors and journalists.

Highly anticipated Phase 2 data for Amgen’s obesity drug show that on average, participants lost about 20% of their weight after one year of treatment, results that put the experimental medicine in the ballpark of blockbuster Eli Lilly product Zepbound. Zepbound and Novo Nordisk’s Wegovy are both administered as weekly injections. Amgen’s drug, maridebart cafraglutide, or MariTide, was tested with doses administered monthly or even less frequently. In the consumer-driven obesity drug market, some analysts say comparable weight loss with the convenience of less frequent dosing could make MariTide stand apart from peer injectable weight-loss medications. The weight loss Amgen reported Tuesday did not plateau, which the company says indicate the potential for even greater weight loss with longer treatment. The pharmaceutical giant plans to publish a fuller picture of the Phase 2 results and present them at a future medical conference. But with the encouraging preliminary data in hand, Amgen said it is preparing to advance MariTide to Phase 3 testing. presented by Market Trends to Watch for Health Systems and Their Specialty Pharmacies The future looks bright for the integrated specialty pharmacy model – for health systems, providers, and most importantly, for patients. By Jake Gaffey, MBA, Chief Strategy Officer at Shields Health Solutions Wegovy and Zepbound are both peptide drugs designed to bind to and activate the GLP-1 receptors. Zepbound is designed to activate a second target called GIP. MariTide is a peptide antibody conjugate. Similar to Zepbound, it offers a dual mechanism of action by targeting both the GLP-1 and GIP receptors. But rather than activating GIP the way Zepbound does, MariTide blocks this receptor. Amgen also says its drug is designed with a long half-life, which enables longer dosing intervals. The Phase 2 test enrolled 592 adults who were living with obesity or overweight. Four doses of the study drug were evaluated. The 20% average weight loss was reported for the cohort who did not have diabetes. In study participants diagnosed with type 2 diabetes, the average weight loss was 17%. In these diabetes patients, treatment with MariTide also led to a 2.2 percentage point reduction, at 52 weeks, in hemoglobin A1C, a measure of blood sugar levels. On measures of safety and tolerability, Amgen’s drug appears to be in line with its peers. Gastrointestinal problems were the most commonly reported adverse events in the Phase 2 study. Amgen said these problems were classified as mild and transient, primarily associated with the first dose. Amgen noted that there was no association between MariTide and changes to bone mineral density, a concern that was raised earlier this month after the inadvertent disclosure of Phase 1 data from a spreadsheet suggested the drug led to bone density changes. The reported weight reductions for MariTide are greater than what was achieved in clinical trials of Novo Nordisk’s Wegovy and on par with Lilly’s Zepbound. But it’s worth noting that Lilly is also developing a next-generation weight loss drug called retatrutide, a peptide engineered to hit three metabolic targets to spark weight loss. In Phase 2 results reported last year and published in The New England Journal of Medicine, treatment with the drug for 48 weeks led to an average 24.2% reduction in weight. Sponsored Post The Funding Model for Cancer Innovation is Broken — We Can Fix It Closing cancer health equity gaps require medical breakthroughs made possible by new funding approaches. By Eve McDavid - CEO of Mission-Driven Tech In a note sent to investors, William Blair analyst Matt Phipps said the weight loss marks posted by MariTide are below market expectations, but the firm still sees potential for the drug. While the addition of a lower initial step-up dose resulted in rates of nausea and vomiting that appear higher than what has been reported with Zepbound and Wegovy, Phipps said these adverse events are largely limited to the first dose, and the overall severity or duration of these problems appear similar to the GLP-1 class. Therefore, MariTide’s ability to offer comparable efficacy and tolerability but with significantly longer dosing intervals still represents a blockbuster opportunity. “Overall, we believe MariTide continues to show a differentiated profile versus currently approved GLP-1 therapies or those in late-stage development, largely due to the ability to be administered with significantly less frequency,” Phipps said. “We believe this will be appealing in what is largely becoming a consumer-driven market, and combined with manufacturing advantages will result in meaningful market share despite being several years behind in development.” But to Leerink Partners’ Thomas Smith, the failure of Amgen’s drug to show differentiation removes a competitive threat to Viking Therapeutics. Viking’s VK2735 also targets and activates the GLP-1 and GIP receptors. In addition to a weekly injectable formulation, Viking is also developing a once-daily oral version of the drug. The ability to offer both injectable and oral formulations is the differentiator that Smith sees could make Viking’s drug best in class. Injectable VK2735 is currently in Phase 3 testing. Viking reported encouraging Phase 1 data for the oral formulation earlier this month. “We believe the MariTide results removed one of the competitive data overhangs for [Viking], and we continue to see [subcutaneous] VK2735 as one of the most promising GLP-1/GIP dual agonist compounds currently in development based on an attractive balance of efficacy and tolerability,” Smith wrote. The MariTide results at one year are from part 1 of the Phase 2 study. Part 2 is evaluating further weight loss with continued treatment and the durability of weight loss after discontinuation of the drug. This second part is also evaluating weight maintenance with less frequent or lower dosing. Amgen said more than 90% of eligible patients from part 1 chose to continue to part 2 of the study.