Novo Nordisk snags high-dose Ozempic approval, turning up the heat on Lilly's Trulicity

Novo Nordisk’s Ozempic, grappling with Eli Lilly’s Trulicity for supremacy of the GLP-1 diabetes market, hit a snag last year when the FDA refused to review a new dosing regimen over the need for more manufacturing info. After resubmitting its application for higher-dose Ozempic in May, Novo on Monday received the regulator’s blessing.

The FDA has approved a new 2-mg dose of once-weekly Ozempic for adults with Type 2 diabetes, building on the drug’s existing green lights at 0.5 and 1 mg. Diabetes aside, Ozempic is indicated to reduce the risk of major cardiovascular events like heart attack, stroke or death in Type 2 diabetes patients with known heart disease, Novo said in a release.

The approval gives Ozempic patients a range of dosing options to rival Lilly’s Trulicity. Back in September 2020, the Indianapolis-based pharma secured a U.S. nod for Trulicity to include higher 3-mg and 4.5-mg doses on top of the GLP-1 med’s original 1.5-mg offering.

Both drugs have shown they work better in diabetes patients when given at higher doses.

Patients with higher blood sugar at baseline who’ve struggled to meet their glycemic targets “now have an additional option with the greater efficacy of the 2-mg dose,” Michael Radin, M.D., executive director at Novo Nordisk, said in an interview.

Michael Radin, M.D.
(Novo Nordisk/Michael Radin)

Aside from new patients with high A1C, Ozempic 2 mg will enable patients already on Novo’s GLP-1 to stay on the med longer, Radin explained.

“[W]e know that diabetes progresses over time and that many patients, even though they’re doing their best—managing their diabetes with medication, in addition to diet and exercise—their glycemic control needs can shift over time,” he said.

Novo plans to roll out Ozempic 2 mg in the U.S. in 2022’s second quarter. The higher-dose semaglutide injectable is already approved in the EU, Canada and Switzerland.

The FDA’s decision leverages data from Novo’s SUSTAIN FORTE trial, which saw patients on Ozempic 2 mg hit “statistically significant and superior” reduction in HbA1c—a commonly used metric for blood sugar—versus the 1-mg dose at Week 40.

Both doses seemed to be safe and well tolerated, too, Novo added. Gastrointestinal side effects were the most common type seen in the study.

Specifically, 34% of patients on Ozempic 2 mg reported gastrointestinal side effects versus 30.8% in the 1-mg cohort—a “small, small difference” that’s “certainly not a concerning safety signal by any means,” Radin pointed out.

That clean safety profile could play in Ozempic’s favor, given analysts have flagged the greater side effect burden as a potential limiting factor for higher-dose GLP-1 meds.

Novo originally submitted its FDA application for Ozempic 2 mg in January 2021, just a few months after Trulicity’s higher-dose nods. Then, in an unusual turn of events, Novo was slapped with a Refusal to File letter in March—an omen of shortfalls in an approval application.

At the time, Novo said the FDA was seeking additional information about a proposed new manufacturing site, adding that it believed no more clinical trial data would be needed for the label expansion.

The company said it refiled Ozempic 2 mg with the FDA in late May.

“I think what’s really important to remember about that refusal to file letter is it was not based on any clinical or safety concerns with the 2 mg dose,” Radin said. It was “based primarily on needing some additional manufacturing data,” which the company was “able to quickly provide and then refile.”

Recently, Novo’s semaglutide triumvirate of Ozempic, Rybelsus and Wegovy has taken center stage in the company’s quarterly earnings reports. The Danish drugmaker is counting on those new offerings in diabetes and obesity to soften the blow once older GLP-1 med Victoza topples over the patent cliff in the next few years.

For the first time last year, Ozempic’s full-year sales significantly eclipsed those of Victoza. Ozempic snared 33.7 billion Danish krone (about $5 billion) in 2021, more than double the 15 billion Danish krone ($2.2 billion) Victoza nabbed for the year.

Eli Lilly’s Trulicity, meanwhile, snagged $6.41 billion in 2021 sales.