Novo's high-dose Rybelsus win tees up regulatory filings—and new rivalries

Even as Novo Nordisk rides the momentum of Rybelsus' hot launch, the company is testing higher-dose versions of the diabetes drug that could broaden its reach in a competitive market. Now, as part of the effort, the company is declaring a late-stage win.

In a phase 3 trial called PIONEER PLUS, Novo's oral semaglutide at 25-mg and 50-mg doses outperformed the approved 14-mg dose, the drugmaker said in a release Friday. Specifically, the experimental doses helped more patients achieve reductions in their HbA1c levels and body weight compared with an approved version of Rybelsus.

The trial tested oral semaglutide, also known as Rybelsus, for 68 weeks at three doses as an add-on treatment to other oral diabetes regimens in patients who needed "treatment intensification," Novo said.

At 52 weeks, both of the higher Rybelsus doses showed a statistically significant reduction of HbA1C, meeting the trial's primary endpoint, Novo said.

For patients with mean baseline HbA1c levels of 9%, those who received the 25-mg and 50-mg doses of oral semaglutide saw reductions of 1.9 percentage points and 2.2 percentage points, respectively. Those figures came in higher than the 1.4 percentage point reduction for the approved Rybelsus dose.

As for body weight changes, patients treated with the 25-mg and 50-mg doses experienced weight loss of 7 kg and 9.2 kg during the study, respectively, compared with 4.5 kg for the approved dose. Patients entered the study with a mean weight of 96.4 kg.

Novo said all doses "appeared to have a safe and well-tolerated profile." The company noted that gastrointestinal adverse events, the most common type during the study, occurred most frequently during dose escalation and happened more often for patients taking the higher doses of the drug. Novo said the "vast majority" of those side effects were mild to moderate and resolved over time.

With the trial win, the company said it plans to seek regulatory approvals for the higher doses in the U.S. and Europe this year. Beyond those markets, the company said the global launch "is contingent on portfolio prioritisations and manufacturing capacity."

In a note to clients, analysts with ODDO BHF wrote that the results are "really good and place the product in direct competition" with Novo's own injectable diabetes drug Ozempic and Eli Lilly's rival Mounjaro. Novo has another phase 3 trial testing the highest oral semaglutide dose in obesity patients, the ODDO team noted.

Rybelsus is one of Novo Nordisk's key launches right now, turning in sales of around $1.63 billion last year. That was more than double the drug's haul from 2021, making it the company's second-biggest growth driver in 2022 behind injectable diabetes drug Ozempic.