By William Elliott, MD, FACP, and James Chan, PharmD, PhD

Dr. Elliott is Assistant Clinical Professor of Medicine, University of California, San Francisco.
Dr. Chan is Associate Clinical Professor, School of Pharmacy, University of California, San Francisco.

Drs. Elliott and Chan report no financial relationships relevant to this field of study.

The FDA has approved a new short-acting insulin as a “follow-on” biologic (FOB) product. Insulin lispro-FOB was approved in the European Union as a biosimilar, but in the United States it was approved using the FDA’s abbreviated approval 505(b)(2) pathway.1 This relies partly on the agency’s finding of safety and effectiveness of the innovator insulin lispro (Humalog) to support approval. This is the second follow-on insulin, after the FDA approved insulin glargine (Basaglar) in December 2015.

INDICATIONS

Insulin lispro-FOB is indicated to improve glycemic control in adults and pediatric patients ≥ 3 years of age with type 1 diabetes mellitus and adults with type 2 diabetes mellitus.2

DOSAGE

The recommended dose is given by subcutaneous administration within 15 minutes before a meal or immediately after a meal. It also can be administered by continuous subcutaneous infusion (insulin pump) or intravenous infusion. The dosage is individualized based on the route of administration and the patient’s metabolic needs, blood glucose monitoring results, and glycemic control goals.1 Insulin lispro-FOB is available in 10 mL multiple-dose vials and 3 mL single-patient use prefilled pens (SoloSTAR).

POTENTIAL ADVANTAGES

Insulin lispro-FOB provides another option and market competition for insulin lispro (Humalog), potentially lowering the cost of therapy.

POTENTIAL DISADVANTAGES

It is not clear whether insulin lispro-FOB is interchangeable with Humalog, as interchangeability has not been demonstrated.

COMMENTS

The safety and effectiveness of insulin lispro-FOB was evaluated in type 1 diabetics and type 2 diabetics.2 In the first study, type 1 subjects were randomized to insulin lispro-FOB (100 units/mL; n = 253) or a non-U.S. approved insulin lispro (100 units/mL; n = 254) immediately before meals. All subjects also received insulin glargine (100 units/mL). Subjects had a mean duration of diabetes of 19 years and a mean baseline HbA1c of 8.08% and 7.99%, respectively. At week 26, insulin lispro-FOB showed an adjusted mean change from baseline of -0.40 compared to -0.46 for the comparator (noninferiority shown). In the study with type 2 diabetics, subjects were randomized to insulin lispro-FOB or an insulin lispro comparator. Subjects had a mean baseline HbA1c of 8.00 and 8.03, respectively. The mean changes from baseline at week 26 were -0.86 and -0.80 (noninferiority shown). Other studies included in the prescribing information were directly from the Humalog prescribing information as permitted by the 505(b)(2) pathway.2,3 These include the use of insulin lispro compared to human insulin in type 2 adults, type 1 adults, and pediatric patients, including continuous subcutaneous infusion (pump).

CLINICAL IMPLICATIONS

Insulin lispro is produced by recombinant DNA technology using a non-pathogenic laboratory strain of Escherichia coli; thus, it qualifies as a biological drug. FDA approval typically goes through the Biological License Application. However, the new drug application 505 (b)(2) applies to some simpler molecules such as insulin, somatropin, and calcitonin.4,5 The interchangeability of biologicals remains uncertain without evidence that patients can be administered a product more than once and that patients can switch back and forth between the follow-on/biosimilar and the reference product with no additional risk or reduced efficacy.6 Insulin lispro-FOB offers an alternative insulin and one that is less expensive than existing insulins. A 10 mL vial for insulin lispro-FOB is $233.50 compared to $274.70 for Humalog. Five 3 mL pens are $450.84 compared to $530.40.

REFERENCES

  1. U.S. Food & Drug Administration. FDA approves Admelog, the first short-acting “follow-on” insulin product to treat diabetes. Available at: http://bit.ly/2DLTKsr. Accessed Jan. 29, 2018.
  2. Admelog Prescribing Information. Sanofi-Aventis, December 2017.
  3. Humalog Prescribing Information. Lilly USA, LLC, May 2015.
  4. Fenwick & West LLP. Follow-on Biological Products — Legal Issues. Available at: http://bit.ly/2EkJS69. Accessed Jan. 29, 2018.
  5. DeGiulio J. FDA approval of biologic drugs under 505(b)(2) expected to increase. Patient Docs, Oct. 13, 2011. Available at: http://bit.ly/2DMhBIC. Accessed Jan. 29, 2018.
  6. U.S. Food & Drug Administration. Prescribing Interchangeable Products. Available at: http://bit.ly/2BABbBG. Accessed Jan. 29, 2018.