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Insulin glargine ‘biosimilar’ meets clinical efficacy in type 2, type 1 diabetes
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SAN FRANCISCO — A new insulin glargine drug, LY2963016 — or LY IGlar — produced results equivalent to an existing insulin glargine product in patients with type 1 diabetes and patients with type 2 diabetes, according to a presenter at the American Diabetes Association’s 74th Scientific Sessions.
“Versions of biologic drugs such as insulin analogs cannot be made identical to the originators; not like the generics that can be generated as identical chemical products. But biologics can be made similar,” Julio Rosenstock, MD, director of the Dallas Diabetes and Endocrine Center, said during his presentation. “In the United States, the originator insulin glargine was approved as a drug through an NDA pathway so a similar version like LY is also required to go through an NDA pathway 505. For this reason, LY in the United States will not be designated by the FDA as a biosimilar, although in other geographies it can be referred to as a biosimilar.”
Rosenstock said, “LY is an insulin glargine product with an identical amino acid sequence to the originator insulin glargine. Even with identical primary structure, protein-based biological manufactured by these processes must be shown to be clinically similar and it has to have a totality of evidence for obtaining regulatory approval.”
Indicated for type 2 diabetes
Rosenstock presented data from the ELEMENT 2 study, a 24-week, phase 3, randomized, double-blind, parallel study conducted to compare efficacy and safety of LY IGlar and insulin glargine, with the main endpoint being non-inferiority (0.3% margin) as measured by change in HbA1c from baseline to 24 weeks in type 2 diabetes on ≥2 oral anti-hyperglycemic medications.
Participants in the study were insulin-naïve (HbA1c ≥7.0% to ≤11.0%) or previously taking insulin glargine (HbA1c ≤11.0%).
At the end of the study, the LY IGlar group (n=376) had an HbA1c of 7.04% and the insulin glargine group (n=380) had an average HbA1c of 6.99%, both similarly significant changes from baseline and non-inferior to one another.
“LY Glargine compared to the originator glargine demonstrated similar glucose-lowering effects, insulin dosages, changes in body weight, hypoglycemia incidence and event rate, adverse event profile, allergic injection reactions and antibody formation,” Rosenstock said. “LY insulin glargine, compared with originator insulin glargine in combination with oral agents provide equivalent efficacy and safety profiles with no clinically meaningful differences in patients with type 2 diabetes.
Secondary efficacy, including fasting plasma glucose and insulin dose, and safety outcomes, including hypoglycemia, were similar between the two groups, as were adverse events.
Efficacy in type 1 diabetes
In another study, Thomas Blevins, MD, ECNU, FACE, FNLA, of Texas Diabetes and Endocrinology in Austin, Tx., presented similar results in patients with type 1 diabetes comparing LY IGlar to insulin glargine, both in combination with pre-meal insulin lispro.
Blevins presented ELEMENT 1, a 52-week, phase 3, randomized, open-label, parallel study in patients with HbA1c ≤11.0 %.
Both those treated with LY IGlar (n=267) and originator insulin glargine (n=268) had within-group significant (P<.001) decreases in mean HbA1c values from baseline, Blevins said. The HbA1c difference at 24 weeks was 0.108% and 0.020% at 52 weeks both which met the pre-specified non-inferiority targets of <0.4 and <0.3%, he told Endocrine Today.Additionally adverse events such as hypoglycemia were similar between treatment platforms, Blevins showed.
“LY insulin glargine compared with insulin glargine, used in combination with insulin lispro, provided equivalent efficacy and a similar safety profile and no clinically meaningful differences in patients with type 1 diabetes,” Blevins said.
Immunogenicity
In a final presentation, Mark A. Deeg, MD, PhD, senior medical officer at Eli Lilly, showed that in both populations, the new drug showed similar immunogenicity to the existing insulin glargine. Using the studies presented by Blevins and Rosenstock, Deeg and colleagues measured anti-insulin glargine antibodies, showing similar detectable antibodies at baseline and throughout treatment in both studies.
Treatment-emergent antibody responses (TEAR) and treatment-emergent allergic events showed no differences between the treatment groups in either study, he confirmed.
“Patients with type 1 and type 2 diabetes showed no treatment differences in proportion of detectable antibodies at baseline and throughout treatment period; incidence of TEAR, relationships between TEAR status and clinical outcomes including HbA1c, basal insulin dose or hypoglycemic rates and no difference in respect to incidence of treatment-emergent allergic events,” Deeg said. “In conclusion, LY insulin glargine and insulin glargine are similar in their immunogenicity profile with respect to efficacy and safety in patients with type 1 and type 2 diabetes.”
For More Information:
Rosenstock J. Abstract 64-OR. Presented at: American Diabetes Association’s 74th Scientific Sessions; June 13-17, 2014; San Francisco.
Blevins T. Abstract 69-OR. Presented at: American Diabetes Association’s 74th Scientific Sessions; June 13-17, 2014; San Francisco.
Deeg MA. Abstract 70-OR. Presented at: American Diabetes Association’s 74th Scientific Sessions; June 13-17, 2014; San Francisco.
Disclosures: These studies were sponsored by Eli Lilly and all authors report financial relationships with the company and other manufacturers.
Perspective
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Matthew C. Riddle Jr., MD
I’m very glad that some direct studies of a biosimilar preparation with an existing glargine formulation has been done and presented. It is the first time.
My opinion is there is no real reason that biosimilars can’t be very clinically effective and safe and scientifically validated with studies like this. We all expect this to happen.
The questions about their use have to do with regulatory approval and consistency of manufacturing quality over time. Those questions haven’t been answered yet. We don’t know what the regulators here and in every other country are going to say about the hoops that a manufacturer of a biosimilar has to jump before the product can be used.
There are a lot of unanswered questions but the scientific data presented today is very encouraging. It supports what we expect to be true and the more safety data presented, the more likely regulators will take a favorable point of view when it’s submitted.
If they’re really equivalent, there’s no medical advantage, but it could be an economic advantage. I don’t think the biosimilar insulins are going to have such a marked drop in price as generic oral drugs do, but any reduction from current levels is a good thing because we’re all struggling with cost.
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