Date: 2014-06-14
Type of information: Presentation of results at a congress
phase: 3
Announcement: presentation of results at the 74th American Diabetes Association Scientific Sessions in San Francisco.
Company: Boehringer Ingelheim (Germany) Eli Lilly (USA)
Product: LY2963016 (biosimilar insulin glargine)
Action
mechanism: LY2963016 insulin glargine is an investigational basal insulin that is intended to provide long-lasting blood sugar control between meals and at night, an integral part of glycemic control. It has the same amino acid sequence as Lantus® and, in most geographic regions, will be submitted for approval as a biosimilar. As the term \'biosimilar\' is a regulatory designation, LY2963016 insulin glargine is considered a biosimilar in some regions but not in others, including the United States.
Disease: type1 diabetes type 2 diabetes
Therapeutic area: Metabolic diseases
Country:
Trial
details: ELEMENT-1 was a 52-week Phase III, randomized, open-label study of 535 patients with type 1 diabetes. The primary objective was to evaluate whether LY2963016 insulin glargine was non-inferior to currently marketed insulin glargine in reducing average blood sugar levels (HbA1c) from baseline at 24 weeks. Patients in the study were also treated with mealtime insulin. Anti-insulin glargine antibodies were also measured to determine the immunogenicity profile of LY2963016 insulin glargine.
ELEMENT-2 was a 24-week Phase III, randomized, double-blind study of 756 patients with type 2 diabetes. The primary objective was to evaluate whether LY2963016 insulin glargine was non-inferior to currently marketed insulin glargine in reducing average blood sugar levels (HbA1c) from baseline at 24 weeks in patients inadequately controlled on two or more oral diabetes medicines. Anti-insulin glargine antibodies were also measured to determine the immunogenicity profile of LY2963016 insulin glargine.
The pharmacokinetics (PK) and pharmacodynamics (PD) of LY2963016 insulin glargine and the EU- and US-approved versions of insulin glargine were evaluated in three Phase I, randomized, double-blind, cross-over replicate euglycemic clamp studies in healthy participants. There was a minimum washout period of one week to separate the doses. Blood samples were collected pre-dose and up to 24 hours post-dose to assess PK, and a euglycemic clamp lasting up to 24 hours was used to assess PD after administration of study insulin at 0.5 U/kg. The PK and PD of two other doses of LY2963016 insulin glargine and currently marketed insulin glargine (0.3 and 0.6 U/kg) were also assessed in a Phase I, randomized, subject- and investigator-blinded study. Twenty-four healthy participants randomly received one of four dosing sequences, receiving a total of two doses each of LY2963016 insulin glargine and currently marketed insulin glargine. There was a minimum washout period of six days to separate the doses. Blood samples were collected pre-dose and up to 24 hours post-dose to assess PK, and a euglycemic clamp lasting up to 24 hours was used to assess PD.
A Phase I randomized, double-blind, crossover glucose clamp study assessed the duration of action of LY2963016 insulin glargine and currently marketed insulin glargine in 20 fasted males with type 1 diabetes. Patients received single administered doses of 0.3 U/kg of both insulin treatments, with a minimum washout period of one week to separate the doses. Duration of action was assessed with a euglycemic clamp lasting up to 42 hours post-dose.
Latest
news: * On June 14, 2014, Eli Lilly and Boehringer Ingelheim Pharmaceuticals presented data showing that LY2963016, the alliance\'s investigational new insulin glargine product, has a similar safety and efficacy profile to currently marketed insulin glargine (Lantus®). Results from these Phase I and Phase III studies were presented at the 74th American Diabetes Association Scientific Sessions in San Francisco. Phase III results: Patients with type 1 diabetes had HbA1c reductions of -0.4 percent (LY2963016 insulin glargine) and -0.5 percent (marketed insulin glargine) at 24 weeks, with similar results at 52 weeks (-0.3 percent for both insulin glargine treatments).Patients with type 2 diabetes had HbA1c reductions of -1.3 percent in both insulin glargine treatment groups at 24 weeks. Approximately one-third of patients with type 1 diabetes reached target HbA1c levels of less than 7 percent at 24 weeks with LY2963016 insulin glargine (35 percent) and marketed insulin glargine (32 percent) treatment. In patients with type 2 diabetes, about half of patients reached these target levels with LY2963016 insulin glargine (49 percent) and marketed insulin glargine (53 percent) treatment. In patients with type 1 diabetes, the incidence of adverse events at 52 weeks was the same between the two insulin treatments (62 percent). The total average hypoglycemia rate (having symptoms attributable to a low blood sugar level and/or blood glucose less than or equal to 70 mg/dL) at 24 weeks was also similar between LY2963016 insulin glargine and marketed insulin glargine (87 and 89 events/patient/year, respectively). The frequency of adverse events was similar between the two treatments in patients with type 2 diabetes (52 percent and 48 percent, LY2963016 insulin glargine and marketed insulin glargine, respectively), including the total average hypoglycemia rate (21 vs. 22 events/patient/year, LY2963016 insulin glargine and marketed insulin glargine, respectively). The Phase III studies also evaluated whether LY2963016 insulin glargine and marketed insulin glargine led to similar development of insulin antibodies and similar effects of immune responses on clinical outcomes. Results showed a similar immunogenicity profile of LY2963016 insulin glargine to marketed insulin glargine. Phase I Study Results: Results from Phase I studies showed that LY2963016 insulin glargine and marketed insulin glargine have similar pharmacokinetic (PK) and pharmacodynamic (PD) profiles, meaning that LY2963016 insulin glargine, when injected under the skin, provided similar amounts of insulin in the blood, with similar characteristics and insulin action (how insulin works to control blood glucose levels), compared to marketed insulin glargine. The PK and PD of LY2963016 insulin glargine and the EU- and US-approved versions of insulin glargine were compared in three studies of healthy participants who received 0.5U/kg doses of two different insulin glargine products on two separate occasions. Results showed similar PK and PD properties of LY2963016 insulin glargine and marketed insulin glargine. The PK and PD properties were similar between LY2963016 insulin glargine and marketed insulin glargine and were consistent across both administered doses in a study comparing the two insulin treatments at two different doses (0.3 and 0.6 U/kg) in healthy participants. In these Phase I studies, LY2963016 insulin glargine was well-tolerated, with no safety concerns noted in adverse events, clinical laboratory tests, vital signs or ECG data. The frequency of adverse events reported was similar between the two treatments. A further Phase 1 study assessed LY2963016 insulin glargine\'s duration of action (how long the insulin works to control blood glucose levels) in patients with type 1 diabetes. Results showed that the average duration of action was 24 and 26 hours for LY2963016 insulin glargine and marketed insulin glargine, respectively. LY2963016 insulin glargine was well-tolerated, with no safety concerns noted in adverse events, clinical laboratory tests, vital signs or ECG data. The frequency of adverse events reported was similar between the two treatments.
In patients with type 1 and type 2 diabetes, LY2963016 insulin glargine was compared to currently marketed insulin glargine, and both products led to significant decreases in average blood glucose levels (HbA1c). LY2963016 insulin glargine demonstrated non-inferiority compared to marketed insulin glargine, and marketed insulin glargine demonstrated non-inferiority to LY2963016 insulin glargine.
The proportion of patients with type 1 diabetes with detectable anti-insulin antibodies was similar between LY2963016 insulin glargine and marketed insulin glargine at baseline (17 percent and 21 percent, respectively) and throughout treatment to 52 weeks (40 percent and 39 percent, respectively).
The proportion of patients with type 2 diabetes with detectable insulin antibodies was similar between LY2963016 insulin glargine and marketed insulin glargine at baseline (6 percent and 4 percent, respectively) and throughout treatment to 24 weeks (15 percent and 11 percent, respectively).
Clinical outcomes, including HbA1c levels, basal insulin dose and total hypoglycemia levels, were not affected by whether or not patients developed antibodies response during the study.
