The glucagon-like peptide-1 (GLP-1) receptor agonist dulaglutide (Eli Lilly’s Trulicity) is one of the most-efficacious type 2 diabetes (T2D) therapies currently available in the United States and Europe. However, the use of this once-weekly injectable agent is typically restricted to the later lines of therapy due to numerous prescribing restrictions as a result of its high price.

Novo Nordisk is developing semaglutide, also a once-weekly subcutaneous GLP-1 receptor agonist, as a follow-on to its class-leading once-daily agent liraglutide (Victoza). Semaglutide has an amino-acid sequence identical to that of liraglutide but has a different chemical spacer group. Despite semaglutide being structurally similar to liraglutide, it is not always the case that comparable macromolecules will interact with the intended target molecule in similar ways. Fortunately for Novo Nordisk, semaglutide’s SUSTAIN-6 CVOT showed cardiovascular (CV) benefits of the same magnitude as liraglutide’s LEADER CVOT.

SUSTAIN-7 is a head-to-head trial comparing semaglutide to dulaglutide. This 40-week trial investigated the efficacy and safety of 0.5 mg semaglutide compared with 0.75 mg dulaglutide and 1.0 mg semaglutide compared with 1.5 mg dulaglutide, when added to metformin. On August 16, 2017, Novo Nordisk announced the SUSTAIN-7 trial results, showing that T2D patients treated with once-weekly semaglutide experienced a statistically significant and superior reduction in glycated hemoglobin (HbA1c) and body weight compared to treatment with dulaglutide (see table).1 AWARD-6, another head-to-head trial, found that once-weekly dulaglutide is non-inferior to once-daily liraglutide for reduction in HbA1c.2

Head-to-Head Trial (SUSTAIN-7) Comparing Semaglutide to Dulaglutide1

Key end points 0.5 mg semaglutide 0.75 mg dulaglutide 1.0 mg semaglutide 1.5 mg dulaglutide
Reduction in HbA1c from mean baseline HbA1c level of 8.2% 1.5% 1.1% 1.8% 1.4%
Treatment target of HbA1c below or equal to 7.0% 69% 52% 79% 68%
More or equal to 5% body weight loss 44% 23% 63% 30%

Using Decision Resources Group’s proprietary conjoint analysis, we modeled physician preferences for three target product profiles (TPP) in our simulator. TPP 1 (blue) represents liraglutide, TPP 2 (orange) is dulaglutide, and TPP 3 (green) is the emerging therapy semaglutide (see figure).3 Based on responses from 60 U.S. and 31 European endocrinologists, the therapy offering the most significant weight loss, reductions in HbA1c levels from baseline, and, CV benefit, would be the preferred therapeutic option for endocrinologists. As such, TPP 3 (semaglutide) was favored over dulaglutide and class leader liraglutide.

Type 2 Diabetes Market Simulations: Share of Preference of Target Product Profiles (GLP-1 RAs)

Note: Data is based on market simulations performed on a set of TPPs, using importance and attribute-level part-worth utilities derived from analysis of the responses of 60 U.S. and 31 European endocrinologists. Share of preference indicates the probability of each product included in the scenario to be chosen. Last updated November 2017.

Price per day was the attribute deemed, by far, the most important for endocrinologists in both regions. The price per day of all agents in our scenario was similar, thus negating its impact on physicians’ choice of agent. Our simulation points to semaglutide’s potential success in the GLP-1 receptor agonist class. Despite having the same dosing schedule as dulaglutide, semaglutide will be able to capitalize on dulaglutide's inferior weight loss, HbA1c reduction, and current lack of CV outcomes data. The results of our simulation also suggest that semaglutide will be able to capitalize on its improved dosing frequency over the market-leading liraglutide. In addition, in our simulation, the likelihood to prescribe semaglutide correlates with surveyed physicians’ assessment of remaining unmet need; the primary concern was having greater reductions in body weight. While this attribute approximates that of liraglutide, semaglutide has the benefit of once-weekly dosing.

Based on the results of SUSTAIN-7, we believe dulaglutide will struggle to retain its current patient share. Further, even if results from dulaglutide’s REWIND CVOT demonstrate CV benefit on par with that of semaglutide (SUSTAIN-6 CVOT), it still may not be enough to elevate dulaglutide’s status among physicians and payers, unless Eli Lilly is successful with aggressive pricing and reimbursement negotiations with T2D payers and clinical detailing strategies with physicians. Finally, if Teva Pharmaceuticals receives FDA approval to market generic liraglutide, uptake of both dulaglutide and semaglutide will be tempered by the availability of a cheaper version of physicians’ favorite, liraglutide, on the market.

1 https://www.novonordisk.com/media/news-details.2127298.html
2 Once-weekly dulaglutide versus once-daily liraglutide in metformin-treated patients with type 2 diabetes (AWARD-6): a randomised, open-label, phase 3, non-inferiority trial. Dungan, Kathleen M et al. The Lancet, Volume 384, Issue 9951, 1349 - 1357
3 https://insights.decisionresourcesgroup.com/disease/type-2-diabetes/unmet-need/detailed-expanded-analysis/

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