Novo Nordisk announced positive results on its pipeline GLP-1 candidate, semaglutide, from the phase IIIa trial, SUSTAIN 4 and 5.
Semaglutide is an experimental analogue of native human glucagon-like peptide-1 (GLP-1) that stimulates insulin and suppresses glucagon secretion in a glucose-dependent manner.
Data from recent trials showed that treatment with semaglutide, administered once-weekly, significantly improved glycemic control, compared to insulin glargine U100, in adults with type 2 diabetes. Results also showed that adults with type 2 diabetes, who were taking metformin with or without sulfonylurea, achieved statistically significant and superior improvements in HbA1c reductions of 1.2% and 1.6% when treated with 0.5 mg and 1.0 mg semaglutide, respectively, versus a 0.8% reduction with insulin glargine U100, from a mean baseline HbA1c of 8.2%.
These results were presented at the American Association of Clinical Endocrinologists 25th Annual Scientific and Clinical Congress (AACE), held in Orlando.
Two new abstracts have been published on semaglutide, a new, acylated, LA GLP-1 analogue with a half-life of 160 h. A pharmacokinetic/pharmacodynamic safety and tolerability study showed pharmacokinetic results compatible with once-weekly dosing and an overall treatment effect on FPG, fasting insulin and fasting glucagon. No safety concerns were identified in this study of healthy subjects. All adverse events were considered mild-to-moderate, the most common being nausea, dyspepsia, vomiting, headache and decreased appetite. No hypoglycemia was reported and no treatment effect was observed on calcitonin. The study also showed reduced hunger and prospective food consumption, as well as increased fullness compared with placebo during standard meals on day 2 (but not day 8). In addition, meal energy intake during an ad lib meal appeared reduced at higher doses on both days 2 and 8. There are no statistical data on the aforementioned parameters in regards to food and energy intake. Mean body weight decreased in all groups, including placebo, at 4 weeks follow-up.
Another study looked at semaglutide at varying doses versus liraglutide or placebo in type 2 diabetes patients in a 12-week, randomized, double-blind, placebo-controlled trial of 411 subjects with a mean A1c of 8.1%. Statistically significant dose-dependent reductions in A1c were seen at all doses of semaglutide ≥0.2 mg as compared with placebo. At higher doses ≥0.8 mg, more subjects reached target A1c <7% than with liraglutide at either 1.2 or 1.8 mg. Body weight was also reduced up to 4.8 kg vs placebo 1.2 kg (p < 0.01 for doses ≥ 0.8 mg). Nausea and vomiting were the most frequently cited adverse events. There were few reports of hypoglycemia in the semiglutide (n = 5) and liraglutide (n = 3) groups without episodes of major hypoglycemia. There were no reports of pancreatitis or treatment-related changes in calcitonin.
The study (SUSTAIN-6) examines the long-term cardiovascular and other safety outcomes of 0.5-mg and 1.0-mg semaglutide, which was administered subcutaneously once weekly and compared with placebo, both in addition to standard of care, in approximately 3,300 people with type 2 diabetes treated for 104 weeks.
“The trial achieved its primary end point of showing noninferiority of major cardiovascular events (MACE) with semaglutide compared with placebo, as well as a statistically significant reduction in cardiovascular risk,” Novo Nordisk said in a press statement. In the trial, around 250 MACE were accrued. The primary end point of the study was defined as the composite outcome of the first occurrence of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. The safety profile of semaglutide in SUSTAIN 6 “was as expected and consistent with previous semaglutide clinical studies,” the company notes.
Mads Krogsgaard Thomsen, executive vice president and chief science officer of Novo Nordisk, added in an interview that, “We are very encouraged by the potential for reduction of CV risk in people with type 2 diabetes with semaglutide based on the results of SUSTAIN-6. In addition to the strong efficacy profile, we have also established the safety profile for semaglutide by concluding the six SUSTAIN trials. “With the strong results from SUSTAIN-6, we look forward to the regulatory filing of semaglutide.”
Semaglutide is also being developed in an oral tablet version for treatment of type 2 diabetes — encouraging phase 2 results were reported with this formulation at the recent ENDO 2016 meeting. And semaglutide is being developed as a once-daily subcutaneous injection for the treatment of type 2 diabetes and weight management, the company adds.
SUSTAIN-6 is the culmination of a global phase 3 clinical development program for semaglutide injection, comprised of six trials and encompassing more than 7000 people with type 2 diabetes.
The other trials were:
- SUSTAIN-1: A 30-week efficacy and safety trial of semaglutide vs placebo in 388 drug-naive people with type 2 diabetes. The results were reported in July 2015.
- SUSTAIN-2: A 56-week efficacy and safety trial of semaglutide vs sitagliptin (Januvia, Merck) once daily as add-on to metformin and/or a thiazolidinedione (TZD) in 1231 people with type 2 diabetes. The results were reported in December 2015.
- SUSTAIN-3: A 56-week efficacy and safety trial of semaglutide vs 2.0-mg exenatide (Bydureon, AstraZeneca) once weekly as add-on to one to two oral antidiabetic drugs in 813 people with type 2 diabetes. The results were reported in September 2015.
- SUSTAIN-4: A 30-week efficacy and safety trial of semaglutide vs insulin glargine once daily as add-on to metformin with or without sulfonylurea in 1089 insulin-naive people with type 2 diabetes. The results were reported in November 2015.
- SUSTAIN 5: A 30-week efficacy and safety trial of semaglutide vs placebo as add-on to basal insulin alone or basal insulin in combination with metformin in 397 people with type 2 diabetes. The results were reported in February 2016.
- At higher doses ≥0.8 mg, more subjects reached target A1c <7% than with liraglutide at either 1.2 or 1.8 mg.
- Body weight was also reduced up to 4.8 kg vs placebo 1.2 kg (p < 0.01 for doses ≥ 0.8 mg).
- There were few reports of hypoglycemia in the semaglutide (n = 5) and liraglutide (n = 3) groups without episodes of major hypoglycemia.
SOURCE: Novo Nordisk Inc.