Novo Nordisk builds cardio claim case for oral semaglutide

Novo Nordisk’s bid to disrupt the diabetes market with an oral formulation of its GLP-1 agonist semaglutide has advanced again with new data showing it is safe for the heart.

The US requires all new diabetes drugs to have data showing they don’t perform worse than placebo on cardiovascular outcomes, and Novo Nordisk has now presented its assessment of oral semaglutide’s impact on heart health at the American Diabetes Association (ADA) congress.

The good news for the Danish drugmaker is that the data found that the GLP-1 agonist was non-inferior to placebo in the PIONEER 6 trial, with 3.8% of patients taking it experiencing cardiovascular complications (heart attack, stroke or cardiovascular death) versus 4.8% of the control group.

Death from any case was cut in half with oral semaglutide – from 2.8% to 1.4% – although the study wasn’t powered to show anything other than non-inferiority.

All eyes are now on an FDA verdict on the drug, due later this year, as it attempts to take on the established injectable GLP-1 agonist therapies.

Earlier at the ADA, Novo Nordisk reported data from two other studies – PIONEER  2 and 4 – showing respectively that oral semaglutide was better at controlling blood sugar in type 2 diabetes than Eli Lilly/Boehringer Ingelheim’s oral SGLT2 inhibitor Jardiance (empagliflozin), and equivalent to once-its own daily GLP-1 injectable Victoza (liraglutide).

With the new cardiovascular safety data in hand, Novo Nordisk’s task is now to convince regulators that its oral version of semaglutide, as well as its once-weekly injectable formulation Ozempic, can actually improve cardiovascular outcomes.

Arch-rival Eli Lilly has already done so with its once-weekly injectable Trulicity (dulaglutide), showing in the larger and lengthier REWIND study that it could cut major adverse cardiovascular events (MACE) in middle-aged and older people with type 2 diabetes by 12% compared to placebo, including those with and without established heart disease. Lilly has already submitted its REWIND data in the US and Europe.

Novo Nordisk opted not to carry out a large-scale study but is instead relying on bundling together all the data from its trials of oral semaglutide in the hope that the overall picture will support a cardiovascular outcomes claim. It has taken a similar tack with Ozempic, building on the non-inferiority data in the SUSTAIN 6 trial.

That will be important if both products are to make headway in the increasingly competitive GLP-1 agonist market, particularly as Ozempic is still playing catch-up against Trulicity, with first-quarter sales of around $210m and $880m respectively.

The convenience of oral semaglutide will be a draw for patients of course, but that could be less compelling if regulators baulk at including a cardiovascular claim for the product. And while Victoza has been standing up fairly well to Trulicity’s assault thanks to its own heart data, its $3 billion-plus in annual sales could be under threat if regulators add a claim to the label of Lilly’s drug.

Meanwhile, in case Novo Nordisk can’t convince regulators of oral semaglutide’s merits first time around, it has a large-scale cardiovascular outcome study called SOUL in preparation that should get underway later this year.

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