Follow-On Insulin Glargine Shows Similar Safety, Efficacy to Lantus in T1D

In 2017, the FDA granted tentative approval to Merck for its follow-on insulin glargine, Lusduna Nexvue, referencing Sanofi’s Lantus. While the product will only gain final approval once Sanofi and Merck conclude litigation over patent infringement, at the time of its approval, the follow-on met all regulatory standards for safety and efficacy, said Merck.

While US patients with diabetes await the launch of the follow-on, which is expected to offer a welcome cost-savings, newly published data from a 52-week clinical trial in patients with type 1 diabetes (T1D) underscore its similar safety and efficacy to the reference insulin glargine.

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Two previous euglycemic clamp studies demonstrated similar pharmacokinetics and pharmacodynamics between the follow-on and the reference, and a prior study in patients with type 2 diabetes demonstrated similar efficacy and safety over 24 weeks. The current study, a phase 3, randomized, multicenter, multinational, open-label study, compared the products’ safety and efficacy in 499 patients with T1D receiving basal and prandial insulin.

After a run-in period of 2 weeks, patients discontinued their prestudy basal insulin and were randomized to receive either the follow-on or the reference, given once daily at bedtime. The primary efficacy endpoint of the study was the change in baseline of glycated hemoglobin (A1C) at week 24, and the primary safety endpoint was anti-insulin antibody (AIA) development over 24 weeks. In total, 89% (n = 214) of patients in the follow-on group and 92% (n = 237) in the reference group completed the initial 24-week period, and 81% (n = 196) and 86% (n = 222), respectively, completed the full 52 weeks.

Both treatment arms had least squares mean A1C decreases from 8.2% at baseline to approximately 7.5% at week 24, and the treatment difference at week 24 was 0.04% (95% CI, −0.10%-0.19%), meeting criteria for equivalence. The treatment difference at week 52 was similar to that of week 24, at −0.02% (95% CI, −0.18%-0.14%). At weeks 24 and 52, the proportions of patients who achieved target A1C levels were similar in the 2 treatment arms. Total hypoglycemia, nocturnal hypoglycemia, and severe hypoglycemia incidence rates were similar between arms.

The proportion of patients who tested positive AIAs at or before weeks 24 and 52 was similar between groups, with the difference in prevalence at the 2 timepoints being −3.9% (95% CI, −11.8%-4.0%) and −2.1% (−9.8%-5.5%), respectively.

The incidence of adverse events (AEs) was similar between groups, with 89.6% of patients in the follow-on arm having 1 or more AE, and 89.9% of the reference group having 1 or more AE. Serious AEs, AEs leading to discontinuation, and drug-related AEs were also similar between arms, and there were no deaths during the study.

The investigators concluded that their findings demonstrate a high degree of clinical similarity between the follow-on and reference insulin glargine in patients with T1D over 52 weeks of treatment.

Reference

Home PD, Lam RLH, Carofano WL, et al. Efficacy and safety of MK-1293 insulin glargine compared with originator insulin glargine (Lantus) in type 1 diabetes: a randomized, open-label clinical trial. [Published online May 15, 2018.] Diabetes Obes Metab. doi: 10.1111/dom.13354.