Materia Medica

Perspective Materia Medica

Semglee® (Insulin Glargine)

WILLIAM BEATHARD, PHARMD AND SAMANTHA DEMARCO, PHARMD, BCPS

Background: Semglee® (insulin glargine) 100 units/mL is a long-acting recombinant human insulin analog recently FDA approved for the treatment of Type 1 and Type 2 diabetes mellitus, June 11, 2020.

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Semglee®, similar to Basaglar FDA approved in 2014, is a biosimilar of insulin glargine that established appropriate physiochemical, pharmacodynamic, and pharmacokinetic bioequivalence with insulin glargine 100 U/mL.

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Clinical trials have demonstrated this once daily insulin glargine biosimilar exhibits noninferiority to insulin glargine with respect to long-term HbA1c reduction. This insulin analog was designed with market competition and cost mitigation in mind.

Safety: As with other long-acting insulins, Semglee® is contraindicated during episodes of hypoglycemia.

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24 and 52-week clinical trials, non-severe treatment-related hypoglycemia was the most common adverse event however the incidence was comparable to insulin glargine with respect to both anytime and nocturnal hypoglycemia.

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Tolerability: Semglee® is approved for subcutaneous administration once daily at any time of the day, administered at the same time every day an reflects the tolerability of other FDA approved insulin glargine analogs.

1 It carries a similar adverse effect profile as demonstrated in other insulin glargine trials. Aside from hypoglycemia, adverse effects occurring in > 10% of patients include upper respiratory tract infections, nasopharyngitis, peripheral edema, hypertension, influenza, sinusitis, and bronchitis.

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At a mean dose of 0.37 units/kg and ~0.3 units/kg in the 24 and 52-week studies respectively, the prevalence of adverse events was similar between groups.

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Weight gain and lipodystrophy are still shared among all insulin and insulin analogs.

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Treatment related discontinuation rates between Semglee® and insulin glargine were comparably low in both studies at 1.1%.

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Efficacy: In clinical trials, Semglee® has been shown to be non-inferior to reference insulin glargine with respect to mean change in HbA1c from baseline.

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Outcomes in HbA1c reduction in type 2 diabetics receiving oral antidiabetic agents were studied in the INSTRIDE 2 study, a 24-week, multicenter, open-label, randomized, parallel-group, phase III non-inferiority study.

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560 patients were randomized to receive Semglee® or insulin glargine at a predefined recommended starting dose of 10 units or 0.2 units/kg. The results of this trial demonstrated a mean change in HbA1c of -0.60% from baseline to week 24 compared to -0.66% seen with insulin glargine (mean in-between group difference 0.06%; 95% CI -0.10, 0.22). Mean HbA1c was also the primary endpoint in the INSTRIDE 1 study, a 52-week, open-label, randomized, phase III study in type 1 diabetics.3 558 patients were randomized to receive either Semglee® or insulin glargine in combination with three times daily meantime insulin lispro. The results of this study revealed a mean change in HbA1c from baseline to week 24 of 0.14% in the Semglee® group and 0.11% in the insulin glargine group (mean in-between group difference -0.05%; SE 0.052, 95% CI -0.148, 0.057).

Secondary clinical endpoints in both studies included changes in insulin dose, fasting plasma glucose (FBG), and self-monitored blood glucose (SMBG)

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The INSTRIDE 2 trial, a non-inferiority study, noted no significant differences in the mean FBG between the Semglee group versus the insulin group (-0.74mmol/L vs -1.05mmol/L, p = 0.071).

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Significant decreases in SMBG were observed similarly in both treatment groups, and the mean daily insulin dose significantly increased over the 24-week study period to 0.37 units/kg and 0.38 units/kg in the Semglee® and insulin glargine group respectively.

The INSTRIDE 1 trial demonstrated similar results at the end of the 52-week study period with no

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Perspective Materia Medica

significant between group differences shown in changes in FBG and SMBG with an increase in daily basal insulin dose of 0.0128 units/kg in the Semglee® group and 0.0043 units/kg in the insulin group.3 Both studies demonstrated slight increases in mean weight from baseline to week 24 and 52.

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Price: The manufacturer price for the 10 mL multiple-dose vial (100 units/mL) is estimated at $98.65 vial. The estimated price for a box of five 3 mL prefilled pens (300 units) is $147.98.5 Weight based dosing precludes accurate estimated monthly pricing based off mean dose of daily insulin evaluated in clinical trials. Mylan offers both copay programs and a patient assistance program to support affordability, touting up to $75 off monthly prescriptions.

Simplicity: Semglee® will be supplied as a 10 mL multiple-dose vial (100 units/mL), 3 mL prefilled pens (300 units) in 3 and 5 pen package sizes, and is compatible with BD Ultra-Fine needles.

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Dosing should be initiated at 0.2 united/kg or up to 10 units/day in insulin naïve patients with type 2 diabetes. In patients with type 1 diabetes, initial dosing of Semglee® is recommended at an estimated one-third of the total daily insulin requirements. Recommended dose conversion between once-daily Semglee® to other once-daily insulin glargine products (300 units/mL) is 80% of the discontinued dose.

Bottom Line: Clinical trials have demonstrated the noninferiority of Semglee® to insulin glargine with respect to mean change in HbA1c. Drug induced adverse event profiles, safety, and tolerability were also comparable.

The recent FDA approval of Semglee® provides an effective and affordable solution to patients who require long acting insulin. This price window allows the biosimilar Semglee® to carve out a niche in type 1 and type 2 diabetics with consistent daily insulin requirements at a fraction of the cost.

Statement: At the time of authorship, William A Beathard is a PGY-1 Pharmacy Resident at UPMC St. Margaret and can be reached at beathardwa@upmc.edu. Samantha DeMarco is a PGY-2 Geriatric Pharmacy Resident and can be reached at demarcosl@upmc.edu. Heather Sakely, PharmD, BCPS, BCGP provided editing and mentoring for this article and can be reached at sakelyh@upmc.edu.

ACMS Bulletin / November 2021

REFERENCES

1.Mylan Specialty L.P. SEMGLEE™ (insulin glargine injection) [package insert]. U.S. Food and Drug Administration website. https://ww w.accessdata.fda.gov/drugsatfda_docs/label/2020/210605s000lbl.pd f. Accessed October 10, 2020. 2. Hoy SM. MYL1501D Insulin Glargine: A Review in Diabetes Mellitus. BioDrugs. 2020 Apr;34(2):245-251. doi: 10.1007/s40259020-00418-x. Erratum in: BioDrugs. 2020 Aug;34(4):541. PMID: 32215829; PMCID: PMC7217807. 3. Blevins TC, Barve A, Sun B, Ankersen M. Efficacy and safety of MYL-1501D vs insulin glargine in patients with type 1 diabetes after 52 weeks: Results of the INSTRIDE 1 phase III study. Diabetes Obes Metab. 2018 Aug;20(8):1944-1950. doi: 10.1111/dom.13322. Epub 2018 May 7. PMID: 29656504. 4.Blevins TC, Barve A, Sun B, Raiter Y, Aubonnet P, Muniz R, Athalye S, Ankersen M. Efficacy and safety of MYL-1501D versus insulin glargine in patients with type 2 diabetes after 24 weeks: Results of the phase III INSTRIDE 2 study. Diabetes Obes Metab. 2019 Jan;21(1):129-135. doi: 10.1111/dom.13495. Epub 2018 Sep 4. PMID: 30112792.

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