No cardio protection indication for Novo's semaglutide - yet

Novo Nordisk has blockbuster hopes for its GLP-1 semaglutide type 2 diabetes drug, which is edging towards approval in major markets – but it won't have a cardiovascular protection indication.

While the FDA granted a cardiovascular protection indication for Novo’s already-marketed GLP-1 Victoza last month, Novo must come up with more data to get the coveted  indication for its successor, although the information could be mentioned in the clinical section of the drug's label.

Now Novo is planning a much larger outcomes trial, beginning next year, to get a definitive answer about semaglutide’s cardiovascular benefits.

Its cardiovascular benefits will be of vital importance, as it will enter an increasingly competitive market where Eli Lilly’s newer GLP-1 Trulicity (dulaglutide) has been stealing market share from Victoza.

Analysts EP Vantage forecast that, once approved, semaglutide could reach revenues of $2.24 billion by 2022 - but its success will hinge on just how good its cardio data will be compared to existing players.

A new era in diabetes drugs was ushered in last year when Boehringer Ingelheim and Lilly’s Jardiance (empagliflozin) was granted FDA approval to promote the drug as being able to reduce the risk of cardiovascular death in patients with type 2 diabetes and established cardiovascular disease, as well as lowering blood sugar levels.

This shift stems from FDA requirements calling for cardiovascular safety studies on all diabetes drugs about a decade ago.

But since then pharma companies have been trying to go one step further and develop diabetes drugs that actually protect the heart.

[caption id="attachment_20125" align="alignnone" width="320"] Mads Krogsgaard Thomsen[/caption]

In a London press briefing, Mads Krogsgaard Thomsen, Novo Nordisk’s chief science officer, said that data from the SUSTAIN 6 study wasn’t sufficient to get the cardiovascular benefit mentioned on semaglutide’s label should it get approved.

“We can talk about it, but it must be in the data and not on the label as an indication,” he said.

This is because SUSTAIN 6 was powered to show semaglutide was no worse than placebo when it came to cardiovascular safety.

But the results from the so-called non-inferiority study were much stronger than expected – showing an overall 26% reduction in the major adverse cardiovascular events (MACE) compared with placebo.

This was almost entirely driven by a 39% decrease in non-fatal stroke, with a non-significant (26%) decrease in non-fatal heart attack and no significant difference in the rate of cardiovascular death.

“What we underestimated was the efficacy of semaglutide,” said Krogsgaard Thomsen.

And because of the small number of actual events, a larger sample size is needed to inform regulators and prescribers about the cardiovascular benefits of semaglutide.

Novo Nordisk is already gearing up for the outcomes trial, which will be conducted using the company’s own network of clinical research associates.

“I think we owe it to the scientific community to get the cardiovascular information on the label,” he added.

Semaglutide hasn't been prioritised for accelerated review by the FDA, however. The company filed it with the US regulator last December, and the FDA is expected to give its ruling by 5 December this year.

Merck's Januvia/Janumet failed to show cardio-protective benefits in its own TECOS cv-outcomes trial, though it also showed no increased risk of heart failure. All told, analysts think Merck's franchise will remain the biggest selling type 2 diabetes drug in 2022, thanks also to its convenient pill form.