Novo Nordisk stokes GLP-1 hopes as weekly semaglutide slashes heart risks by 26%

Novo Nordisk knew its blockbuster GLP-1 diabetes drug Victoza would lose market share to new rival Trulicity and its convenient weekly dosing. But the Danish drugmaker doesn’t intend to let that continue for long.

Its own weekly GLP-1 med, semaglutide, is on tap for an approval filing this year--and now, that drug has proven it can cut the risk of cardiovascular problems by 26%, according to data from the SUSTAIN 6 trial presented on Friday at a medical meeting in Munich. Semaglutide cut stroke risks by 39% and heart attack by 26%, though the latter was statistically nonsignificant.

These are powerful numbers that could help Novo solidify its GLP-1 dominance. The company now plans a longer and larger trial to rack up further evidence, Reuters reports. With 3,300 patients, SUSTAIN 6 involved just two years of treatment and was designed to prove safety rather than benefits.

Victoza itself proved to cut the risk of heart attack, stroke and cardiovascular death together by 13% in its 9,000-patient LEADER trial, which lasted more than three and a half years. Victoza slashed the risk of CV death by 22% and delivered a 15% lower risk of death, period. Victoza patients also saw a 22% lower risk of advanced diabetic kidney disease. 

But semaglutide’s 26% reduction in overall risks--represented by a composite endpoint called MACE--is even more promising, and Novo sees the CV data as an important competitive edge. The follow-up trial would begin as soon as semaglutide is approved.

“[T]he cardiovascular outcomes trial data is very unique,” Novo CMO Todd Hobbs told FiercePharma earlier this year, when asked how semaglutide could hope to compete in the increasingly crowded GLP-1 field, not only with doctors and patients, but cost-conscious payers as well.

“Semaglutide would be the fourth weekly to market,” Hobbs went on to say, at the American Diabetes Association meeting in June, “but the data we’ve seen so far against the weekly competitors is really strong, and we will go to payers with that.”

One red flag did pop up in the SUSTAIN 6 trial, which was presented at the European Association for the Study of Diabetes meeting and simultaneously published by the New England Journal of Medicine: Patients in the semaglutide arm were more likely to develop problems with diabetic retinopathy, an eye disorder that can cause blindness. During the course of the study, 5 semaglutide patients went blind, compared with one in the placebo group.

Novo R&D chief Mads Krogsgaard Thomsen said the larger, follow-up outcomes study would help clarify those risks as it sheds new light on the CV benefits. It “might ‘wash away’ this effect and maybe even show an improvement,” Thomsen optimistically told Reuters on site at the meeting.

Novo knows all too well that the diabetes landscape is getting rocky. Payers are trading discounts and rebates for exclusive or preferred formulary placement, and they’re toughest on competitive drug classes--such as GLP-1, which encompasses meds from GlaxoSmithKline and AstraZeneca, in addition to Lilly, BI and Novo. In one recent disappointment for Novo, Victoza was shut out of Express Scripts’ preferred formulary for 2017, the second year in a row, while its competitor Trulicity nabbed a spot.

Making a case with new trial data can obviously help, and there’s not much better than proof that a diabetes drug doesn’t just control blood sugar, but also offers real benefits to the heart and vascular system.

Victoza and semaglutide aren’t the only diabetes meds to have that proof, however. Eli Lilly and Boehringer Ingelheim’s SGLT2 drug Jardiance was the first diabetes treatment to prove not only safe for the heart, but beneficial, too. In its own outcomes trial, Jardiance cut the risk of cardiac death, heart attack and stroke by 14%, and reduced the risk of cardiac death by a whopping 38%. The two companies have asked the FDA to add that claim to Jardiance’s label, and won narrow backing from an expert advisory panel in June.

Novo has its own hopes for a label claim on Victoza, and, eventually semaglutide. And it’s now prepping for cross-class competition by recruiting patients for a head-to-head study pitting weekly semaglutide against Jardiance. HbA1C levels will be the primary endpoint, and body weight and hypoglycemic events among a list of secondary endpoints.

Novo is also testing an oral version of semaglutide, which would be taken daily. After encouraging Phase II results last year, the drugmaker advanced the oral formulation into Phase III with its PIONEER program. Eight studies are planned as part of that program, including a newly added head-to-head against Victoza, and the first is set to read out next year. A daily injectable is also in development for Type 2 diabetes and weight loss.

That’s a big investment in clinical trials, and Novo is counting on the bet paying off. As Sydbank analyst Soren Lontoft told Reuters, “Semaglutide is one of the drugs which is going to drive growth for Novo Nordisk in the coming years--their entire GLP-1 business in fact.”

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