Key points from the evidence | Diabetes mellitus type 1 and type 2: insulin glargine biosimilar (Abasaglar) | Advice

Summary

In 2 randomised controlled trials (RCTs) insulin glargine biosimilar (Abasaglar) was as effective as insulin glargine (Lantus) at reducing HbA1c levels in people with type 1 and type 2 diabetes. The safety profile of Abasaglar is comparable to that of Lantus.

Regulatory status: Insulin glargine biosimilar 100 units/ml (Abasaglar) received a European marketing authorisation in September 2014 and was launched in the UK in September 2015. It is the first biosimilar insulin glargine to be launched in the UK and as part of the licensing process, has been shown not to have any clinically meaningful differences from the originator biological medicine in terms of quality, safety and efficacy.

Effectiveness

Insulin glargine biosimilar 100 units/ml (Abasaglar) once daily was non‑inferior to insulin glargine 100 units/ml (Lantus) in people with type 1 diabetes (treatment difference 0.11% points [1.18 mmol/mol] p>0.05) for change in HbA1c from baseline (1 open‑label RCT, n=535, 24 weeks).
Insulin glargine biosimilar 100 units/ml (Abasaglar) once daily was non‑inferior to insulin glargine 100 units/ml (Lantus) in people with type 2 diabetes (treatment difference 0.05% points [0.57 mmol/mol] p>0.05) for change in HbA1c from baseline (1 double‑blind RCT, n=756, 24 weeks).

Safety

The safety profile of Abasaglar is comparable to that of Lantus and as expected for an insulin product. No additional safety signals were detected with regard to hypoglycaemia, allergic reactions or injection site reactions and the immunogenicity profiles are comparable (European public assessment report [EPAR]).
The Abasaglar summary of product characteristics lists the same contraindications, cautions and undesirable effects as for Lantus and lists hypoglycaemia as a very common adverse reaction.

Patient factors

Abasaglar is given once daily by subcutaneous injection, and is available as 100 units/ml in cartridges or as a pre‑filled pen.
Across the 2 RCTs similar numbers of people withdrew because of adverse events with Abasaglar compared with Lantus (1% compared with 2% in people with type 1 diabetes and 2% compared with 3% in people with type 2 diabetes).
Abasaglar is a new insulin product and people with diabetes need to understand the differences between Abasaglar and several other new insulin products that have recently become available to minimise the risk of medication error.
All biological medicines, including biosimilar medicines, should be prescribed by brand name so that products cannot be automatically substituted at the point of dispensing.
The choice of whether a patient receives a biosimilar or originator biological medicine rests with the responsible clinician in consultation with the patient.

Resource implications

The cost of Abasaglar cartridges 100 units/ml, 5×3 ml for the pen or Abasaglar pre‑filled pen 100 units/ml, 5×3 ml is £35.28 (excluding VAT; prices taken from MIMS, November 2015). This is 15% less than the cost of Lantus.
Comparable costs for other standard‑strength basal insulins range from £17.50 to £72.00 for 5x3 ml cartridges or pre‑filled pens (excluding VAT; prices taken from MIMS, November 2015).
The cost of Abasaglar and other basal insulins will depend on the preparation chosen and the insulin dosage used.

Introduction and current guidance

Diabetes mellitus is a group of metabolic disorders in which blood glucose is persistently raised. Type 1 diabetes is a long‑term hormonal deficiency disorder treated with insulin replacement therapy. This is supported by active management of other cardiovascular risk factors, such as raised blood pressure and disturbed blood lipid levels. Type 2 diabetes is a chronic metabolic condition characterised by insulin resistance and insufficient pancreatic insulin production, resulting in high blood glucose levels. It is commonly associated with obesity, physical inactivity, raised blood pressure, disturbed blood lipid levels and a tendency to develop atherosclerosis, and therefore is recognised to be associated with an increased cardiovascular risk. NICE has published guidance on the management of type 1 and type 2 diabetes in adults with recommendations on insulin therapy and an individualised approach to diabetes care. A biosimilar medicine (or biosimilar) is a biological medicine that is developed to be highly similar to an existing biological medicine (the reference medicine). The active substance of a biosimilar and its reference medicine is essentially the same biological substance but, just like the reference medicine, the biosimilar has a degree of natural variability. When approved, this variability and any differences between the biosimilar and its reference medicine will have been shown not to affect safety or effectiveness. In the development of a biosimilar, there is no requirement to demonstrate clinical benefit to patients per se as this has been shown for the reference medicine. Instead, biosimilars undergo a comprehensive regulatory process which demands extensive comparability studies that demonstrate similarity to the reference medicine. Biosimilars have the potential to offer the NHS considerable cost savings. However the choice of whether a patient receives a biosimilar or originator biological medicine rests with the responsible clinician in consultation with the patient.

Full text of introduction and current guidance.

Product overview

Insulin glargine biosimilar (Abasaglar) is licensed for the treatment of diabetes mellitus in adults, young people and children over 2 years. Abasaglar is a basal insulin for once daily use and is bioequivalent to insulin glargine (Lantus). Abasaglar is available as cartridges of 100 units/ml for use in the reusable pen or as a pre‑filled Abasaglar pen 100 units/ml. It should be noted that the Abasaglar device is not the same as that of the originator (Lantus). Abasaglar cartridges cannot be used in the re‑useable pen devices produced for Lantus.

Full text of product overview.

Evidence review

This evidence summary is based on the 2 phase III studies of insulin glargine biosimilar (Abasaglar) in people with type 1 and type 2 diabetes (ELEMENT 1 [Blevins et al. 2015] and ELEMENT 2 [Rostenstock et al. 2015], respectively). The objective of these randomised controlled trials (RCTs) was to compare the efficacy (in terms of HbA1c reduction) and safety of the biosimilar Abasaglar) and the reference medicine Lantus in people with type 1 and type 2 diabetes.

In ELEMENT 1 in people with type 1diabetes (n=535) and ELEMENT 2 in people with type 2 diabetes (n=756), once‑daily Abasaglar was non‑inferior to once‑daily Lantus (primary end point) and Lantus was non‑inferior to Abasaglar (secondary end point), demonstrating equivalent efficacy of both medicines. A similar reduction in HbA1c from baseline to 24 weeks was seen in both treatment groups, with a difference between groups of 0.11% (1.20 mmol/mol), 95% confidence intervals (CI) −0.00 to 0.22 (−0.00 to 2.40 mmol/mol) in ELEMENT 1 and 0.05% (0.60 mmol/mol), 95% CI −0.07 to 0.18 (−0.80 to 1.90 mmol/mol) in ELEMENT 2. The treatment difference was below the pre‑specified non‑inferiority margins of 0.4% and 0.3% in both studies. The study in people with type 1 diabetes, ELEMENT 1, was continued to 52 weeks and non‑inferiority of Abasaglar to Lantus was confirmed at this further time point.
There were also no statistically significant treatment differences in either study for secondary outcomes such as the proportion of participants meeting HbA1c targets or the mean change in body weight between people using insulin glargine biosimilar (Abasaglar) and those using insulin glargine (Lantus).
In both ELEMENT 1 and ELEMENT 2, the number of participants with any adverse event, any serious adverse event or withdrawing because of an adverse event was similar in the Abasaglar and Lantus groups (p>0.05 for all treatment differences).
In both studies there was no treatment difference between Abasaglar and Lantus for the most frequently reported adverse events. In people with type 1 diabetes (ELEMENT 1) these were nasopharyngitis (16.4%), upper respiratory tract infection (8.0%) and diarrhoea (4.1%),whereas the incidence in people with type 2 diabetes (ELEMENT 2) was 5.7%, 4.5% and 3.0% respectively. Hypoglycaemia was reported in 4.7% of people with type 1 diabetes in ELEMENT 1. The majority of adverse events were mild to moderate in severity.
In ELEMENT 1 and ELEMENT 2, total mean hypoglycaemia rates (events per person per year), as well as rates of nocturnal or severe hypoglycaemia, were not statistically significantly different between Abasaglar and Lantus in either study. As would be expected the total incidence of hypoglycaemic episodes was greater in people with type 1 diabetes than in people with type 2 diabetes, where 60% of participants were insulin naive at entry into the study.
There are no published clinical studies comparing Abasaglar with Lantus in children and young people. However, the summary of product characteristics includes reference to paediatric studies with Lantus.
Medication errors are an important risk with insulin glargine biosimilar (Abasaglar) 100 units/ml. The MHRA Drug safety update advises that healthcare professionals and people with diabetes should understand the differences between Abasaglar and several other new insulin products that have recently become available.
The European public assessment report (EPAR) states that both studies provided data on patients switching from Lantus to Abasaglar at the same dose regimen, and no difference in dose changes after titration to tighten blood glucose control was reported between the 2 treatment arms.

Full text of evidence review.

Context

Basal insulin supply for people with type 1 and type 2 diabetes can be provided by:

NPH (isophane) insulin (for example, Insulatard, Humulin I or Insuman Basal) or
long‑acting insulin analogues: insulin glargine (Abasaglar, Lantus or high‑strength Toujeo), insulin detemir (Levemir) or insulin degludec (Tresiba).

Biosimilar and reference biological medicines that have the same international non‑proprietary name (INN) are not presumed to be identical in the same way as generic non‑biological medicines. The MHRA recommend that it is good practice to prescribe all biological medicines, including biosimilars, by brand name to prevent automatic substitution at the point of dispensing (Drug Safety Update 2008). Also see the NHS England publication, What is a biosimilar medicine? for more information.

NICE guidance on the management of type 1 and type 2 diabetes in adults recommends once daily insulin glargine can be considered for some people in certain situations (see the type 1 diabetes and the type 2 diabetes guidelines for more information).

The manufacturer estimates that the annual average cost of Abasaglar 100 units/ml once daily is £214.44 per person with type 1 diabetes and £278.77 per person with type 2 diabetes. This is based on estimated average daily doses of 25 units per day in type 1 diabetes and 40 units per day in type 2 diabetes.

Full text of context.

Estimated impact for the NHS

Biosimilar medicines have the potential to offer the NHS considerable cost savings, especially as they are often used to treat long‑term conditions. Abasaglar is a biosimilar insulin glargine of standard strength 100 units/ml. It has a list price 15% lower than Lantus, however the cost of Abasaglar and other basal insulins will depend on the preparation chosen and the insulin dosage used. The European Medicines Agency (EMA) has approved Abasaglar based on extensive comparability studies that demonstrate similarity to Lantus. Abasaglar is licensed for the same indication as Lantus (treatment for adults, young people and children aged 2 years and above with diabetes mellitus) and the summary of product characteristics includes the same contraindications and warnings. See also the NHS publication 'Answers to commonly asked questions about biosimilar versions of insulin glargine' for more information. In the 2 phase III clinical studies (which included people with type 1 and type 2 diabetes) there was a subgroup that was switched from Lantus to Abasaglar at the same dose regimen and no difference in dose changes after titration to tighten glucose blood control was reported between the 2 treatment arms. However, in a Drug safety update the MHRA advised that some dose adjustment may be needed for some patients.

Full text of estimated impact for the NHS.

About this evidence summary

'Evidence summaries: new medicines' provide summaries of key evidence for selected new medicines, or for existing medicines with new indications or formulations, that are considered to be of significance to the NHS. The strengths and weaknesses of the relevant evidence are critically reviewed within this summary to provide useful information for those working on the managed entry of new medicines for the NHS, but this summary is not NICE guidance.