GLP-1 agonists such as Novo Nordisk’s semaglutide and SGLT2 inhibitors like AstraZeneca’s Farxiga are already butting heads in the treatment of diabetes. But AstraZeneca’s biopharma business president, Ruud Dobber, said he’s not concerned about a potential clash between the two classes as they reach more patients.
At the recent European Society for Cardiology (ESC) congress, Novo showed that Wegovy, or once-weekly semaglutide at the 2.4-mg dose, can significantly improve symptoms of heart failure in some patients.
That could mean additional competition for AZ’s Farxiga because, as Dobber noted, the success of the AZ med is driven in large part by its use in heart failure. But Dobber said he doesn’t view GLP-1 drugs as a threat for the SGLT2 class—at least for now.
Farxiga should be able to hold its own because it’s an oral drug, whereas Wegovy is administered via an injection, Dobber argued. Farxiga also bears an approval for treating chronic kidney disease in patients at risk of progression, while Wegovy has yet to show renal benefits.
In heart failure, Farxiga boasts a broad label and can be prescribed regardless of a patient’s ejection fraction status or body weight. Novo’s new Wegovy win covered only obese patients with heart failure with preserved ejection fraction (HFpEF), although Novo noted that most people with HFpEF are overweight or obese. HFpEF makes up nearly half of all heart failure cases.
Meanwhile, Wegovy’s STEP-HFpEF trial didn’t answer the key question of whether the Novo drug can reduce heart failure events or deaths. As the authors of a New England Journal of Medicine editorial accompanying the STEP-HFpEF data pointed out, those hard endpoints are crucial to determine the eventual roles of GLP-1 agonists and SGLT2 inhibitors in heart failure management.
Those cardiovascular outcomes results typically take a large trial and a long time to obtain, Dobber noted. For its part, AZ’s Farxiga won its heart failure nod based on a phase 3 trial of 6,263 patients. Farxiga will go off patent around 2028.
In a separate trial, Novo’s Wegovy cut the risk of a cardio death, heart attack or stroke by 20% compared with placebo and standard of care in overweight or obese patients with established cardiovascular disease. That trial enrolled 17,604 people and tested the Novo drug for up to five years in people 45 and older. Patients in that trial had cardiovascular disease, but not heart failure.
Farxiga, known as Forxiga in Europe, had its own win to celebrate this past weekend. The ESC just updated its treatment guidelines to recommend SGLT2 inhibitors as first-line treatments for heart failure. The backing will “significantly simplify prescribing of SGLT2s for physicians,” Dobber said.
But AZ’s drug faces competition from within its own class, most notably from Eli Lilly and Boehringer Ingelheim’s Jardiance, which is also approved for heart failure. Tuesday, both drugs appeared among the first 10 drugs up for Medicare price negotiations.
Outside the SGLT2 class, Lilly has a GIP/GLP-1 dual agonist called Mounjaro. The drug is a rising star in diabetes and likely will be approved soon in obesity.
Farxiga is currently the most used SGLT2 inhibitor in the world, but it lags Jardiance in the U.S. with about 30% to 35% market share stateside. And all the publicity around the GLP-1 class has created somewhat of a halo effect for Lilly.
Publicity is nice, but physicians look for products that they’re comfortable with, Dobber said.
“In the end of the day, it comes back to the belief of an individual physician, which product and which indication is most suitable to make the choice,” he said.
AZ has been working on the GLP-1 pathway, too, including with its FDA-approved Bydureon. But the British pharma recently dropped twice-daily cotadutide to focus on its weekly GLP-1/glucagon candidate AZD9550, which is in early stages of development.
Meanwhile, AZ its still focused on advancing Farxiga, and its strategy includes testing various combinations. AZ currently has three Farxiga combinations in phase 2 development, with readouts expected in late 2023 or early 2024, according to Dobber. One combo is testing the inclusion of baxdrostat, which AZ got from its $1.8 billion acquisition of CinCor Pharma earlier this year.
Dobber called baxdrostat and Farxiga a “very attractive combination.” Baxdrostat, a selective aldosterone synthase inhibitor, has shown promise in lowering blood pressure, which is a risk factor for diabetes patients and nondiabetics with kidney disease, he noted.
“Based on the data we’ve seen, we feel bullish and excited that that combination will help a lot of chronic kidney disease patients, irrespective whether they have diabetes or nondiabetes,” the AZ executive said.