Proposed Biosimilar Liraglutide Shows Non-Inferiority to Reference Drug for Type 2 Diabetes

A proposed biosimilar for liraglutide (Levim Biotech LLP) demonstrated non-inferior efficacy and similar safety compared to the reference drug liraglutide (Victoza; Novo Nordisk A.S, Denmark) for type 2 diabetes mellitus (T2DM), according to results of a study published in Diabetes Research and Clinical Practice.

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In 2014, liraglutide, a glucagon-like peptide 1 receptor agonist, was approved by the FDA. It has been shown to have a clinically and significant reduction in glycated hemoglobin (hbA1c), when given either as a monotherapy or combined with other antidiabetic therapies, according to the study authors.

In the phase 3 clinical trial (registered in India), investigators aimed to further evaluate the proposed biosimilar beyond preclinical characterization studies, preclinical repeated dose toxicity studies, and pharmacokinetic assessments. Investigators included individuals with T2DM who were also undergoing treatment with other oral hypoglycemic agents. It involved 14 centers in India, with those aged 18 to 65 years who had HbA1c between 7% and 10%, according to the study.

All individuals in the study were dosed with 0.6 mg of the investigational biosimilar at baseline and underwent dose titration after at least 1 week, increasing to 1.2 mg. After the 1 week, the dose was titrated to 1.8 mg based on self-monitoring of glucose in the blood. The HbA1c was measured at baseline, week 12, week 18, and week 24, according to the investigators. The primary endpoint included the mean change in reduction in HbA1c percentage from baseline to week 24 when compared to the reference product. Investigators also checked for non-inferiority. Safety endpoints included adverse events (AEs) and serious AEs during the 24-week period, according to the study authors.

In total, 256 individuals were included in the study, with 128 individuals in the proposed biosimilar group and the reference liraglutide group, respectively. Overall, 123 individuals in the biosimilar liraglutide group and 119 individuals in the reference liraglutide group completed the study, according to the investigators. There was a total of 137 males and 119 females of South Asian ethnicity in the study, with a mean age of 50 years in the biosimilar group and 50.9 years in the reference group. Investigators added that the discontinuation rate was comparable in the groups. The mean baseline HbA1c value was 8.5% in the biosimilar group and 8.6% in the reference group, according to the study authors.

The study authors reported a reduction in HbA1c percentage for both treatment groups at all time points, with a difference of –0.04 at week 24. For the secondary endpoint, the proportion of individuals who achieved a reduction of HbA1c by more than 0.5% during the treatment period was comparable with 86 individuals in the biosimilar group and 88 individuals in the reference group.

Additionally, investigators said that at the different time points, the proportion of individuals with that reduction in HbA1c was also comparable. The study authors also said that the proportion of individuals achieving an HbA1c reduction of more than 1% was also comparable in the 2 groups at week 24. The results also showed that the proportion of individuals who achieved a less than 7% HbA1 c from baseline to week 24 was higher in the reference product, through it was not statically significant with 36 individuals and 25 individuals, respectively.

Furthermore, the study authors reported that the proposed biosimilar was safe and well tolerated, and the safety profile was consistent with the reference liraglutide.

References

Krishnan K, Raman S, Anand Moses CR, et al. Phase 3 efficacy and safety trial of proposed liraglutide biosimilar for reduction of glycosylated hemoglobin (HbA1c) in patients with Type 2 diabetes mellitus. Diabetes Res Clin Pract. doi:10.1016/j.diabres.2023.111034