SEMGLEE® clinical trials demonstrated highly similar efficacy and safety to LANTUS.
SEMGLEE Efficacy
SEMGLEE offers highly similar clinical benefits compared with LANTUS including duration of action, rate of hypoglycemia and effect on changes HbA1c and fasting plasma glucose from baseline when used as directed.
In the randomized, double blind, phase 3 INSTRIDE trials conducted in patients with type 1 and type 2 diabetes, SEMGLEE and LANTUS demonstrated highly similar results regarding changes in HbA1c, and FPG from baseline.
| INSTRIDE 1 Study Design2 |
|---|
| Primary Endpoint - Change in HbA1c from baseline to week 24. |
| Secondary Endpoints - Included changes in FPG, insulin dose, SMBG and immunogenicity. |
| Multicenter, open-label, randomized, parallel group, 52-week trial. |
| 558 patients with type 1 diabetes, with or without prior insulin
use: 336 males and 222 females, aged 18-65 years, BMI 18.5-35kg/m2. |
| Treated with once-daily insulin glargine for more than 3 months and with HbA1c ≤9.5% at screening. |
| Patients began a 6-week run-in period and were titrated with first reference insulin glargine and then insulin lispro, as needed, to ensure good diabetes control as determined by the investigator. |
| At randomization, there was a 1:1 (unit for unit) conversion of reference insulin glargine to SEMGLEE (100 U/mL of insulin glargine) and of prestudy mealtime insulin to insulin lispro. |
In the INSTRIDE 1 clinical trials, SEMGLEE demonstrated non-inferiority to reference insulin glargine in both adult and pediatric patients with Type 1 Diabetes.1
In the INSTRIDE 1 trial, the mean change in HbA1c from the baseline to week 24 among Type 1 diabetic patients was not non-inferior between SEMGLEE and the reference insulin glargine groups.2
Change in HbA1c from baseline to week 24 in all and insulin-naïve patients with SEMGLEE and reference insulin glargine3
Mean change in fasting plasma
glucose from baseline at week 24 and 52
| INSTRIDE 2 TRIAL DESIGN3 |
|---|
| Primary Endpoint: Based on change in HbA1c from baseline to week 24. |
| Secondary Endpoint: Included changes from baseline in basal insulin dose as well as fasting plasma glucose (FPG), SMBG and immunogenicity. |
| Multicenter, open-label, randomized, parallel group, 24-week trial. |
| 560 patients with type 2 diabetes, 312 males and 248 females,
aged 18-65 years, BMI 18.5-40 kg/m2. |
| For the first 12-weeks, basal insulin was titrated without altering oral antidiabetic drug doses (the most common were metformin, 70.4%,; glimepirides 22.0%, glipizides 14.6% and metformin hydrochloride 11.1%). During the following 12 week maintenance period, all oral antidiabetic treatments were unchanged. |
In the INSTRIDE 2 study, the clinical efficacy (mean change in HbA1c and FPG levels from baseline) of SEMGLEE is comparable to LANTUS in the treatment of hyperglycemia in patients with type 2 diabetes mellitus.
INSTRIDE 3 Trial
The FDA’s approval of SEMGLEE as biosimilar to, and interchangeable with LANTUS, is based on evidence that showed the products are highly similar and that there are no clinically meaningful differences between SEMGLEE and LANTUS in terms of safety, purity and potency (safety and effectiveness).4
The evidence also showed that SEMGLEE can be expected to produce the same clinical result as LANTUS in any given patient and that the risks in terms of safety or diminished efficacy of switching between SEMGLEE and LANTUS is not greater than the risk of using LANTUS without such switching.4
| INSTRIDE 3 TRIAL DESIGN4 | |
|---|---|
| Primary Endpoint: Change in HbA1c from baseline to week 36. | |
| Secondary Endpoints: Change from baseline in fasting plasma glucose (FPG), eight-point self-monitored blood glucose (SMBG) profile and insulin dose per unit body weight, and immunogenicity at week 36, in addition to occurrence of hypoglycaemic events (30-day rate), nocturnal hypoglycaemic events, and adverse events (AEs). | |
| Multicenter, open-label, randomized, parallel-group, phase 3 study. | |
| Individuals who successfully completed 52 weeks of reference insulin glargine treatment in the INSTRIDE 1 study and provided written informed consent were eligible, for a total of 127 participants with T1DM randomized: 64 to MYL-1501D and 63 to reference insulin glargine, 77 males, 50 females, aged 18-65 years, BMI 18.5-40 kg/m2. | |
| The reference insulin glargine sequence group continued reference insulin glargine for 36 weeks. The treatment-switching sequence group received SEMGLEE for weeks 0 to 12, reference insulin glargine for weeks 12 to 24, and SEMGLEE for weeks 24 to 36; after week 36, all participants resumed their baseline treatment and had a safety follow-up visit at week 40. |
INSTRIDE 3 shows that switching patients between SEMGLEE and LANTUS resulted in equivalent efficacy and safety.
Overall incidences of any hypoglycemic event or nocturnal hypoglycemic event were comparable between the groups who switched between SEMGLEE and LANTUS and who received only LANTUS over a 36-week period, with no significant difference observed between treatment sequences at any visit. Overall, immunogenicity profiles were comparable between the SEMGLEE switch group and LANTUS-only treatment sequences.
References:
- SEMGLEE® (insulin glargine-yfgn) injection. Prescribing Information. 2023. Biocon Biologics Inc. Cambridge, MA.
- Blevins TC, Barve A, Sun B, Ankersen M. Efficacy and safety of MYL-1501D vs insulin glargine in patients with type 1 diabetes after 52 weeks: Results of the INSTRIDE 1 phase III study. Diabetes Obes Metab. 2018;20(8):1944‐1950.
- Blevins TC, Barve A, Sun B, et al. Efficacy and safety of MYL-1501D versus insulin glargine in patients with type 2 diabetes after 24 weeks: Results of the phase III INSTRIDE 2 study. Diabetes Obes Metab. 2019;21(1):129‐135.
- Blevins, Thomas & Barve, Abhijit & Raiter, Yaron & Aubonnet, Patrick & Athalye, Sandeep & Sun, Bin & Muniz, Rafael. (2019). Efficacy and Safety of MYL‐1501D Versus Insulin Glargine in Patients With Type 1 Diabetes Mellitus: Results of the INSTRIDE 3 Phase 3 Switch Study. Diabetes, Obesity and Metabolism. 22. 10.1111/dom.13904.
- FDA News Release. FDA Approves First Interchangeable Biosimilar Insulin Product for Treatment of Diabetes. https://www.fda.gov/news-events/press-announcements/fda-approves-first-interchangeable-biosimilar-insulin-product-treatment-diabetes
