At ADA, Sanofi Reveals Data on Proposed Insulin Aspart Biosimilar, SAR341402

Insulin maker Sanofi is currently developing a proposed biosimilar of insulin aspart (NovoLog), made by Novo Nordisk. In 3 late-breaking poster presentations at the American Diabetes Association (ADA) 79th Scientific Sessions, held June 7-11, 2019, in San Francisco, California, researchers presented data on the biosimilar, SAR341402.

First, researchers reported on pharmacokinetic (PK) and pharmacodynamic (PD) study data of the biosimilar versus brand-name NovoLog and NovoRapid in 30 male patients with type 1 diabetes (T1D).¹

Patients were randomized to receive 0.3 U/kg of the biosimilar and each of the reference products in separate periods in this double-blind, 3-treatment, 3-period crossover study. PK and PD were assessed by euglycemic clamp up to 12 hours.

The investigators report that the 90% CIs for the treatment ratios for the primary and main secondary PK and PD end points (peak serum concentration, area under the concentration—time curve [AUC] up to the last measurable concentration, AUC, bodyweight-standardized AUC up to 12 hours, and maximum smoothed glucose infusion rate) were all within the prespecified acceptance margin of 0.80-1.25.

Adverse events were similar among arms, and no safety concerns were noted.

Data were also presented for a phase 3 study of the biosimilar.² The 6-month, randomized, controlled, open-label study compared the biosimilar to the reference insulin in 597 adults with T1D or type 2 diabetes.

Patients were randomized to receive the biosimilar (n = 301) or the reference (n = 296) as multiple daily injections together with insulin glargine. The primary end point was change in glycated hemoglobin (A1C) change, with a prespecified noninferiority margin of 0.3%, from baseline to week 26.

The investigators report that the biosimilar was noninferior to the reference: The change from baseline to week 26 was —0.38 (standard error [SE], 0.042) in the biosimilar arm versus –0.30 (SE, 0.041) in the reference arm.

There were no differences in the percentages of patients reporting hypoglycemia, and immunogenicity and safety profiles were also similar.

Finally, a third team of researchers reported on the safety of the biosimilar when administered through an insulin pump.³

This randomized, open-label, 2-arm crossover study in 45 patients with T1D had a primary endpoint of assessing the number of patients with infusion-set occlusions with the biosimilar versus the reference when using an insulin pump.

The percentage of patients reporting at least one infusion-set occlusion was 32.6% patients receiving the biosimilar and 27.9% of patient receiving the reference. The number of patients with at least 1 event of unexplained hyperglycemia was 72.1% in the biosimilar arm and 74.4% in the reference arm.

According to the investigators, the biosimilar and the reference were both well tolerated, and there was no difference in the safety profiles when used in infusion pumps.

While insulins are currently regulated as drugs and follow-ons in the US context, they will become regulated as biologics and biosimilars in March 2020.

References

1. Kapitza C, Nosek L, Lehmann A, Schmider W, Rotthaeuser B, Nowotny IK. Comparative PK and PD of the rapid-acting insulin aspart SAR341402, NovoLog, and NovoRapid in subject with T1D. Presented at: American Diabetes Association 79th Scientific Sessions; June 7-11, 2019; San Francisco, California. Poster 130-LB.

2. Garg SK, Wernicke-Panten K, Wardecki M, et al. Similar efficacy, safety, and immunogenicity in people with diabetes using SAR341402 or insulin aspart: Gemelli 1 study. Presented at: American Diabetes Association 79th Scientific Sessions; June 7-11, 2019; San Francisco, California. Poster 129-LB.

3. Thrasher J, Polsky S, Hovsepian L, et al. Safety assessment of SAR341402 and NovoLog when administered through an insulin pump. Presented at: American Diabetes Association 79th Scientific Sessions; June 7-11, 2019; San Francisco, California. Poster 137-LB.