New Insulins, Biosimilars, and Insulin Therapy

Abstract

A dvances in insulin formulations continue to be important for diabetes management, but clinical safety and efficacy need to be established. Today, the increased availability of continuous glucose monitoring already allows a more intricate analysis of clinical insulin action than was previously possible. This permits an assessment of whether these new insulins provide a better means for achieving optimal glycemic control beyond HbA1c, which is increasingly receiving scientific and regulatory acceptance. This comes at a time when rapid developments in the device area, as showcased by the U.S. Food and Drug Administration (FDA) approval of the hybrid closed loop (MiniMed 670G, Medtronic) in September 2016, ask for pharmacological advances to facilitate the development of closed-loop pump systems (i.e., artificial pancreas) potentially being a treatment option for insulin-dependent patients with both type 1 and type 2 diabetes.At the same time insulin may no longer be the only treatment approved for type 1 diabetes, as sotagliflozin (Lexicon/Sanofi), a novel, oral antidiabetic agent has achieved success in several phase 3 clinical trials. Indeed, Jorge Insuasty, senior vice president and head of global development at Sanofi, announced in the summer of 2017 that they will be pursuing regulatory submissions for the adjunct treatment of type 1 diabetes worldwide, which may have a significant impact on the way we treat type 1 diabetes in the future. This year's attention focused on the first-ever next-generation mealtime insulin to be launched globally. Fiasp (NovoNordisk) is the brand name for fast-acting insulin aspart. After the ultra-fast rapid-acting insulin aspart was approved by the European Commission and other authorities early in 2017, it was launched in April in Canada, Germany, and the United Kingdom and will be coming soon to more European countries, while the FDA approval process is still ongoing. At the same time, clinicaltrials.gov lists completed phase 1 trials with Eli Lilly's new ultra-rapid insulin LY900014, which have yet to be published. In contrast, the December 2014 Collaboration Research and License Agreement between Lilly and Adocia for the development of BioChaperone Lispro, Adocia's ultra-rapid insulin for treatment in people with type 1 and type 2 diabetes, was terminated in January 2017.Regarding the long-acting analogs, the year provided evidence for their efficacy in reducing the hypoglycemia risk with the ultra-long-acting insulins Toujeo (Sanofi) and Tresiba (NovoNordisk) as well as for the cardiovascular safety of Tresiba, providing reassuring data for clinical practice.In the second year after the first biosimilar insulin (BioIns) got market approval in the European Union and the United States (not as a BioIns due to the current regulatory situation in the United States), some changes in the insulin marketplace occurred, but nothing overwhelming happened. In the United States some insurance companies switched from Lantus to Basaglar (insulin glargine by Lilly/Boehringer Ingelheim

New Insulins, Biosimilars, and Insulin Therapy

“…The randomized, double-blind, four-period, crossover study, examining PK and PD with a head-to-head comparison of the two rapid-acting insulin analogs Lispro and Aspart and the two ultra-rapid counterparts Liumjev and FiAsp raised the possibility that ultra-rapid Lispro may have a clinical advantage over other bolus insulins. However, the PRONTO clinical trial program, as described previously by Klaff et al, Blevins et al, and Bode et al, showed similar data to the ONSET program for FiAsp (13) with no major effect on HbA1c.…”

“…Efficacy and safety of insulin glargine 300 units/mL (Gla-300) versus insulin glargine 100 units/mL (Gla-100) in children and adolescents (6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)…”

“…Participants from INSTRIDE 1 who completed 52 weeks of reference insulin glargine treatment were randomized 1:1 to the reference sequence (n = 63; insulin glargine for 36 weeks) or to the treatment-switching sequence (n = 64; MYL-1501D [weeks 0-12], insulin glargine [weeks [12][13][14][15][16][17][18][19][20][21][22][23][24], MYL-1501D [weeks [24][25][26][27][28][29][30][31][32][33][34][35][36]). The primary efficacy endpoint used to show equivalence between the two treatment sequences was a change in HbA1c from baseline to week 36.…”