Semglee

Product Profile:

Insulin glargine-yfgn (Semglee)

Drug Category: insulin, long-acting

Target Indications: To improve glycemic control in adult and pediatric patients with type 1 diabetes mellitus (T1D) and in adults with type 2 diabetes mellitus (T2D).

Manufactured by Biocon; marketed by Viatris and Biocon

Summary: The product was originally designated as Myl-1501D. Mylan (now Viatris) submitted an application for approval via the 505(b)(2) NDA pathway in September 2017, because insulin was still regulated under the Food, Drug, and Cosmetics Act of 1962. Subsequently, the FDA elected not to approve the agent in 2018 and 2019. Prior to the approval of Semglee, the FDA took action under section 351(a) in accordance with the Biologics Price Competition and Innovation Act to decree that all insulin copies would be treated as biosimilars effective March 23, 2020. As the FDA approval process for Semglee was already underway, legislative action allowed the approval to move forward under the 505(b)(2) pathway, culminating in an FDA approval June 11, 2020. The product was launched August 31, 2020.

The partners subsequently submitted a 351(k) application for Semglee, seeking interchangeable status with the reference product Lantus. This was granted on July 28, 2021.

A second insulin glargine biosimilar, by Eli Lilly (Rezvoglar, insulin glargine-aglr), was approved on December 17, 2021. This product has not earned the interchangeable designation. As of March 2022, there are now, besides the originator product Lantus, two insulin glargine follow-on agents and two biosimilars.

About the Manufacturer

Viatris was formed when Mylan and UpJohn were combined in 2020. Subsequently on February 28, 2022 Biocon Biologics Limited acquired Viatris’ rights for biosimilar products. Biocon Biologics is a subsidiary of Biocon, Ltd located in India. They manufacture and commercialize complex generics, biosimilars, insulins, and novel biologics. Currently Biocon Biologics has two other FDA approved biologics (Fulphila (pegfigrastim-jmdb) and Ogivri (trastuzumab-dkst) available in the US market.

News, Commentary, and Intelligence

Competitor Products and Manufacturer Analysis

Semglee was the first insulin glargine designated biosimilar and interchangeable to the reference product Lantus. Two other insulin glargine follow-on agents were approved in the US (Basaglar by Eli Lilly and Lusduna by Samsung Bioepis and Merck, the latter was no longer available in the US as of 2018). This market is also complicated by the availability of nonbranded “authorized” versions of reference and biosimilar agents.

INSULIN GLARGINE BIOSIMILARS AND FOLLOW-ONS APPROVED BY THE FDA

Manufacturer

Brand Name and Designation

Filing Date

Approval Date

Eli Lilly

Basaglar (insulin glargine)

2014

FDA approved December 16, 2015 as a 505(b)2 drug

Viatris/Biocon

Semglee (insulin glargine-yfgn)

2018

Approved first as 505(b)2 in June 2020; FDA approved as biosimilar and interchangeable July 28, 2021

Eli Lilly

Rezvoglar (insulin glargine-aglr)

N/A

FDA approved December 17, 2021; not yet marketed

INSULIN GLARGINE BIOSIMILAR IN DEVELOPMENT

Company Name

Product Name

Stage of Development

Lannett/YiChange HC ChangJiang Pharmaceutical Co., Ltd

TBD

An Investigational New Drug application was completed in January 2022. The pivotal clinical trial was scheduled to begin by March 2022 (anticipated completion by early 2023). Possible BLA in late 2023.

Insulin Wars: Biosimilar Sustainability May Soon Be an Issue With Civica’s Announcement

(March 4,, 2022) The announcement on March 4 that Civica, the private-public partnership among 25 health systems, plans, and foundations, will be producing low-cost insulin in the near future may shake biosimilar insulin competition to its foundations.

Second Insulin Biosimilar to Get FDA’s Nod—Eli Lilly’s Rezvoglar™ to Enter the Glargine Market

(December 24, 2021) The complexity of the insulin competition continues to boggle the mind. On December 17, 2021, Eli Lilly received FDA approval of its Rezvoglar (insulin glargine-aglr), a product that is biosimilar to Sanofi’s Lantus®, and marks the second insulin glargine agent approved this year.

Basaglar® Competition Had a Strong Effect on Insulin Glargine Net Prices

(October 21, 2021) According to a study published in JAMA Internal Medicine this month, the approval and launch of the follow-on insulin glargine product Basaglar turned the tide on rising costs for this long-acting insulin.

Insulin Follow-ons, Authorized Generics, Biosimilars, and Interchangeables: A Stew of Competitive Ingredients

(October 13, 2021) With the Food and Drug Administration’s (FDA’s) recent approval of the first interchangeable insulin, Viatris and Biocon’s Semglee®, some questions may begin to be answered with respect to payer coverage, automatic substitution, and their potential for success in the marketplace. However, unlike the other biologic drug categories, there are additional levels of complexity among the insulins that may affect future competition.

New Entrant into Insulin Market Wants to File as Biosimilar in 2022

(June 15, 2020) Lannett, a maker of generic pharmaceutical products, disclosed that it has been in talks with the Food and Drug Administration (FDA) about bringing a biosimilar version of insulin glargine into clinical trials.

Mylan/Biocon’s Insulin Drug Saga Ends With an Approval

(June 12, 2020) Although Mylan and partner Biocon did not beat the March 22, 2020 deadline for the transition of new insulins to biosimilar status, they were able to secure a 505(b)2 FDA approval for their insulin glargine follow-on agent.

Transition Day for Insulins, Other Products

(March 24, 2020) On Monday, March 23, biologic products formerly evaluated for approval under section 505 of the Federal Food, Drug, and Cosmetic Act (FD&C Act) are now approvable only under section 351 of the Public Health Service Act (PHS Act). That means many categories of drugs will now be considered eligible for biosimilar competition.

The Appropriations Bill Alters Insulin Biosimilar Rules

(December 20, 2019) Closing out the week before the holidays, the House and Senate’s Appropriations Bill specified two significant passages that affect the March 22, 2020 transition date for insulins being approved under the 351(k) pathway. Here’s a summary of these two points.

Insulin Transitions: A Dead Zone in the Gap Year, and Other Considerations

(September 27, 2019) In this two-part conversation with one of the real go-to experts in the biosimilar field and US regulatory process, we talk with Dr. Gillian Woollett about the upcoming transition for insulins and other pharmaceuticals in March 2020, when they become regulated as 351(k) biosimilars.

Semglee: A Less Expensive Insulin Option

The Journey to an Interchangeable Insulin

Clinical Trials of Semglee

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.

A randomized, open-label, 52-week, phase 3 study was conducted in 558 patients with type 1 diabetes. Patients received MYL-1501D (N = 280) or the originator product (N = 278) Lantus, once daily with three times daily mealtime insulin lispro. The primary outcome was change in glycated hemoglobin (A1c) from baseline to week 24. The secondary endpoints were changes in fasting plasma glucose, insulin dose, self-monitored blood glucose (SMBG) and immunogenicity from baseline, as well as the occurrences of hypoglycemia, nighttime hypoglycemia, and adverse events to week 52.

The mean change in the primary endpoint (A1c level) at week 24 was 0.14% in the group receiving MYL-1501D compared with 0.11% in the Lantus group. This small difference was deemed nonsignificant by the researchers. The results for the secondary outcomes were also similar at week 52. Selected secondary outcomes results at week 52 are shown in the Table below.

Secondary Endpoint in Type 1 Diabetes

MYL-1501D
(N = 280)

Lantus
(N = 277)

Mean change in fasting plasma glucose level (mmol/L)

0.23

0.43

Mean change in 8-point SMBG level

–0.082

–0.082

Mean change in daily insulin dose

0.0278

0.0138

Any hypoglycemic event

273

269

Severe hypoglycemia

11

13

Serious adverse events were similar in both groups, with 18 (6.4%) in the MYL-1501D group and 22/278 (7.9%) in the reference product group. Hypoglycemia was the most commonly observed serious adverse event, occurring in 7 and 10 patients, respectively. The investigators concluded there were no clinically meaningful differences between the groups for the safety parameters.

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.

MYL-1501D was also tested in patients with type 2 diabetes. This investigation was an open-label design, conduced as a randomized, parallel-group non-inferiority study. The study population comprised insulin-naïve and insulin-non-naïve patients with type 2 diabetes mellitus who were also receiving oral antidiabetic drugs. The 560 patients received either MYL-1501D (N = 277) or Lantus (N = 283) for 24 weeks. The primary efficacy endpoint was change in A1c from baseline. Secondary endpoints included changes in fasting plasma glucose, insulin dosage, SMBG, and adverse events that included hypoglycemia.

The mean change in A1c was similar in each group (–0.60% in the study group vs. –0.66% in the control group). Based on the prespecified benchmarks of equivalent efficacy established by the investigators, they concluded that MYL-1501D was non-inferior to Lantus.

The secondary outcomes were also similar between the two groups.

The safety profile was similar for both products.

Safety in Type 2 Diabetes

MYL-1501D
(N = 276)

Lantus
(N = 282)

Any hypoglycemic event

130

136

Severe hypoglycemia

0

1

Any serious adverse event

8

9

Based on the similar efficacy and safety profile, the investigators concluded that the two insulin glargine products produced similar outcomes.

Interchangeability

Efficacy and safety of MYL-1501D versus insulin glargine in people with type 1 diabetes mellitus: Results of the INSTRIDE 3 phase 3 switch study.

To demonstrate interchangeability of Semglee to the reference product Lantus, an extension phase was added to the INSTRIDE Study 1 outlined above. The researchers sought to determine whether patients could safely switch between Semglee and Lantus. Patients with type 1 diabetes who completed 52 weeks of the INSTRIDE Study 1 could participate in the open-label, randomized, parallel-group, phase 3 trial.

Patients were assigned to one of two groups: 63 patients continued to receive the reference product and 64 patients received Semglee for 12 weeks, followed by the reference product for 12 weeks, and finally Semglee for 12 weeks. The primary endpoint was change in A1c level from baseline to week 36. Secondary endpoints included fasting plasma glucose level and insulin dose as well as safety and immunogenicity profiles.

At week 36, the mean change in A1c concentration was similar between the two groups (–0.05% vs. –0.06%, respectively). Secondary efficacy endpoints were also similar between the two groups at week 36.

Secondary Endpoints for Interchangeability

Switching Group (N = 64)

Lantus (N = 63)

Fasting plasma glucose  (mg/dL)

166.1

175.0

Insulin dose, basal (U/kg)

0.32

0.36

Insulin dose, mealtime (U/kg)

–0.35

–0.37

Insulin dose, total daily (U/kg)

–0.68

–0.73

Observed hypoglycemia was similar between the two groups as were the number of treatment-emergent adverse events (TEAEs).

Switching Group (N = 64)

Reference Product
(N = 63)

Hypoglycemic event rate, episodes (mean)/30 days total

2.3

2.3

Nocturnal hypoglycemic event rate, episodes (mean)/30 days

0.2

0.3

Severe hypoglycemic event rate, episodes (mean)/30 days

0

0

Patients with detectable antibodies overall

71.9%

55.6%

Cross-reactive insulin antibody % binding (mean)

9.9

7.3

Patients with ≥1 TEAE

64.1%

66.7%

Patients with ≥1 grade 3–5  TEAE

3.1%

4.8%

The investigators concluded that switching patients between Semglee and the reference product glargine did not result in different efficacy or safety outcomes.

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