On a roll, Novo's star obesity drug Wegovy shows benefits in patients with heart failure

Just a few short weeks after Wegovy posted a major cardio outcomes win, Novo Nordisk has chalked up another heart-related victory for its semaglutide star.

In the phase 3 study STEP HFpEF, semaglutide 2.4 mg (Wegovy’s dose) bested placebo at reducing symptoms and physical limitations in patients with obesity and heart failure with preserved ejection fraction (HFpEF).

Treatment with the drug, a GLP-1 agonist, also led to greater improvements in exercise function and more weight loss versus a dummy drug, according to study results published in The New England Journal of Medicine Friday.

For patients with HFpEF, the heart muscle contracts properly but the ventricles don’t relax. For patients with reduced ejection fraction, the heart muscle doesn’t contract properly. Both conditions cause diminished blood flow.

HFpEF comprises roughly half of all heart failure cases, Novo Nordisk pointed out in a Friday press release. About 80% of people with HFpEF are overweight or obese, which is linked to a higher burden of symptoms, worse physical function and lower quality of life.

In the study, once-weekly semaglutide administered over a year helped patients lose an average of 13.3% of their body weight, versus a 2.6% average loss in the placebo group.

Further, the drug significantly improved patient scores on the Kansas City Cardiomyopathy Questionnaire, a measure of the symptoms and physical limitations of HFpEF. It also helped patients increase their walking distance over a six-minute span.

“Today’s news heralds a possible fundamental paradigm shift in how cardiologists approach HFpEF in people with obesity," Mikhail Kosiborod, M.D., the trial's lead investigator, said in a statement.

The results potentially add a “much needed” option for HFpEF patients, especially for those who are also overweight or obese, Yigal Pinto, M.D., Ph.D., noted in an editorial accompanying the data drop.

“How these findings translate to hard end points remains to be established and will be important in determining the role of GLP-1 agonism as compared with SGLT2 inhibition in patients with heart failure with preserved ejection fraction,” Pinto explained.

This marks Wegovy’s second cardio win in less than a month. Earlier in August, the drug cut the risk of major adverse cardiovascular events by 20% versus placebo and standard of care in large phase 3 trial. Specifically, investigators measured Wegovy’s 2.4-mg dose for its ability to cut the risk of a cardio death, heart attack or stroke.

Based on that trial win, Novo Nordisk said it expects to seek a label expansion to include the cardiovascular risk-reduction data in the U.S. and Europe this year.

Those cardio outcomes could make a big difference in terms of coverage, too.

Analysts at Intron Health opined earlier this month that Medicare is “almost certain” to allow reimbursement of obesity drugs following Wegovy’s prior cardio readout.

Wegovy has enjoyed immense popularity since its debut in 2021, so much so that Novo has periodically had to deal with supply constraints on the obesity blockbuster. 

Only months into Wegovy’s launch, CDMO Catalent’s deliveries of Wegovy were halted after the FDA found various problems at the contract manufacturer's syringe-filling facility in Brussels. The plant shut down again in August 2022 when another FDA inspection found lapses.

More recently, Novo is reported to have tapped Thermo Fisher to help chip in on Wegovy pen filling in North Carolina. 

Novo Nordisk soon plans to launch Wegovy in more countries, though it will do so in a "constrained" manner as it will take years before the company and its partners can meet global demand, CEO Lars Fruergaard Jorgensen told Reuters on Friday.