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.
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.
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.
Photo: Patrick T. Fallon/Bloomberg, via Getty Images
