Type 1 diabetics will not have an add-on medication to insulin anytime soon. After testing the GLP-1 analogue Victoza in the autoimmune form of the disease, Novo Nordisk has decided that the modest blood-sugar lowering benefit does not justify the increased hypoglycaemia risk.
The decision should cast doubt on whether the only other GLP-1 in active type 1 research, GlaxoSmithKline’s late entry Tanzeum, can outperform Victoza. Patients and specialists will have to look to next year’s phase III readout for Jardiance to find out if a non-insulin medication can help effectively control the disease.
Victoza at 1.2mg and 1.8mg a day with background insulin therapy lowered blood sugar from a baseline of 8.2% to 7.7%, compared with 7.9% for patients taking insulin and a placebo. These doses met a statistical test for non-inferiority, but with a significantly increased risk of hypoglycaemia for which the Danish group did not provide numbers.
Expectations of success had been very low; Bank of America-Merrill Lynch was alone among major analysts to have forecast sales in this indication, $3.9bn by 2023. This would have been a significant addition to type 2 sales, which are now estimated to reach $3.7bn by 2020, according to EvaluatePharma’s consensus. One advantage of the low expectations is that Novo’s decision not to file for approval in type 1 will not change investors’ views of the company.
Victoza has been the pace-setter in the GLP-1 class, but is now seeing its market share chiselled away by later entrants such as Trulicity. As this class and others like the DPP-IVs and SGLT-2s mature, their owners are looking for new niches into which they can fit to expand sales (Upcoming events: Novo, Lilly, Merck and Pfizer look for diabetes edge, July 31, 2015).
Bryan Garnier analyst Eric Le Berrigaud wrote today that a better fit for the type 1 population might be Novo’s Xultophy, a combination of Victoza and the long-acting insulin Tresiba, or weekly GLP-1 semaglutide, which yielded positive phase III data in type 2 diabetics last month (Novo Sustains momentum with first weekly GLP-1 data, July 13, 2015). Neither Xultophy nor semaglutide has any active trials listed in type 1.
Back to insulin
It no doubt comes as a disappointment to patients, however. The only way to control type 1 disease is with insulin, with both basal and mealtime injections necessary to keep near normal insulin levels. Any assistance in achieving tight glycaemic control could help prevent complications.
The next potential milestone for a non-insulin medication could be the readout of Boehringer Ingelheim’s and Lilly’s Ease-2 trial of Jardiance, next year. The InTandem1 trial of the SGLT-1/2 sotagliflozin is also expected next year; that project has long been awaiting a partner, so it has much to prove, but success in inTandem1 could see it yet deliver a licensing deal for Lexicon.
After that, AstraZeneca and Bristol-Myers Squibb’s Farxiga is expected to conclude its type 1 Depict 1 and 2 studies in 2017.
There is not necessarily any reason to believe that the SGLT-1 class will perform any better in type 1 disease. However, Jardiance has surprised by showing a cardiovascular benefit (Cardiovascular radiance for Jardiance, August 21, 2015). Maybe it has another ace up its sleeve.