Novo Nordisk's high-dose Ozempic stalls at FDA's door on lack of manufacturing data

The FDA has sent a refusal to file letter to Novo Nordisk for its application of Ozempic at an increased dosing strength, requesting more manufacturing data. (Novo Nordisk)

Novo Nordisk’s been eyeing a weekly dosing regimen for its GLP-1 diabetes med Ozempic to better compete with Eli Lilly’s rival drug Trulicity. But that quest has hit a setback.

The FDA refused to review the new dosing regimen—an unusual step indicating serious shortfalls in an approval application. To file again, Novo needs to offer up more manufacturing data, the Danish drugmaker said Monday.

The Type 2 diabetes injection is currently approved at 0.5-mg and 1-mg doses given once a week. The new dose would be 2 mg weekly and could set Novo up to fend off a forthcoming Lilly drug, tirzepatide, in addition to Trulicity.

The agency is looking for additional information about a proposed new manufacturing site, Novo said, adding that it believes no more clinical trial data will be needed for approval of the label expansion.

The company said it plans to resubmit the application in the second quarter of 2021.

RELATED: Novo Nordisk, following in Lilly's Trulicity footsteps, files higher Ozempic dose for diabetes

The site in question is located in Novo’s home country, Denmark, a company spokesperson said. The company last year made a series of investments in upgrading and expanding its production facilities in Kalundborg, Denmark, which are responsible for making active pharmaceutical ingredients for its diabetes drugs.

COVID-19 has delayed or derailed several drug approvals as the FDA’s limiting its on-site manufacturing inspections during the pandemic. But the current FDA refusal-to-file letter isn’t related to an inspection, the spokesperson said.

Novo filed the stronger 2-mg dose in January, shortly after Lilly added the higher 3-mg and 4.5-mg doses to the U.S. label of its rival once-weekly GLP-1 drug Trulicity.

RELATED: Novo Nordisk plots $1.3B in spending as it expands API production—and advances new oral meds

Bernstein analyst Ronny Gal has projected that the low doses will be the “workhorse” versions of the two drugs, but the increased efficacy with higher doses could help the companies reach patients whose glucose levels aren’t adequately managed by the lower doses. In a tight race for leadership in the U.S. GLP-1 market, every additional expansion counts.

For now, Novo’s GLP-1 franchise—which also includes its older Victoza and Ozempic’s sister oral drug Rybelsus—holds a small lead, with total U.S. GLP-1 market share of 49.8% as of January, ahead of Trulicity’s 44.7%. Ozempic and Trulicity were also neck and neck in new-to-brand share, according to a Novo Nordisk presentation last month based on IQVIA data.

RELATED: Lilly has its Ozempic-beating data from a head-to-head diabetes trial. Should Novo Nordisk be worried?

Besides the existing options, Lilly has dual GIP/GLP-1 candidate tirzepatide in the works, making its higher-dose Ozempic even more important, competitively speaking. Tirzepatide just topped Ozempic in a head-to-head phase 3—at least at the current FDA-approved doses—at reducing blood sugar levels and body weight. 

Buoyed by its GLP-1 franchise’s fast growth, Novo expects DKK 8 billion ($1.28 billion) in capital spending this year, mainly to add capacity for diabetes APIs at existing sites, the company said in February.

The company already has a new $2 billion API production facility in Clayton, North Carolina. Novo broke ground on that 825,000-square-foot plant in 2016 and has said it expects to win approval to produce for the U.S. market this year.

On top of the 2-mg regimen of Ozempic for diabetes, Novo also awaits an FDA decision on a 2.4-mg version of the under-the-skin semaglutide drug as an obesity treatment. In addition, it has begun a phase 3 trial with Rybelsus, or oral semaglutide, at the higher 25-mg and 50-mg doses, compared with the currently approved 14-mg strength.