Insulin Glulisine, injection (human analogue), 100 units per mL, 3 mL, 5, Apidra®, Apidra SoloStar®, March 2007
Public summary document for Insulin Glulisine, injection (human analogue), 100 units per mL, 3 mL, 5, Apidra®, Apidra SoloStar®, March 2007
Page last updated: 29 June 2007
Public Summary Document
Product: Insulin Glulisine, injection (human
analogue), 100 units per mL, 3 mL, 5, Apidra®, Apidra
SoloStar®
Sponsor: sanofi-aventis australia pty ltd
Date of PBAC Consideration: March 2007
1. Purpose of Application
The submission sought an unrestricted listing for the treatment of
Type 1 and Type 2 diabetes mellitus.
2. Background
Insulin glulisine had has not previously been considered by the
PBAC.
3. Registration Status
Insulin glulisine is TGA-registered for the treatment of type 1 and
type 2 diabetes mellitus in adults and children older than 12 years
who require insulin for the control of hyperglycaemia.
4. Listing Requested and PBAC’s view
Unrestricted benefit
The PBAC had no objection to the requested listing.
5. Clinical place for the proposed therapy
Insulin glulisine will provide another treatment option for
patients with Type 1 diabetes or Type 2 diabetes requiring a
combination of a basal and a prandial insulin to maintain an
appropriate glycaemic control.
6. Comparator
The submission nominated insulin lispro as the main comparator
while noting that insulin aspart had been listed on a
cost-minimisation basis compared to insulin lispro. The PBAC
considered the comparator appropriate.
7. Clinical trials
The scientific basis of comparison for Type 1 diabetes in terms of
efficacy involved a 26-week randomised, open-label, head-to-head
trial (Study 3001) comparing insulin glulisine with insulin lispro.
Comparison of safety was based on a 26-week extension phase of the
same trial.
Studies that compare insulin glulisine with insulin lispro
in the treatment of Type 1 diabetes
| Study | Publication title & citation |
| Study 3001 (week 1-26) | Main publication: Dreyer M et al (2005) Efficacy and safety of insulin glulisine in patients with Type 1 diabetes. Hormone & Metabolic Research 37(11): 702-707 Abstract only: Prager R (2004) Efficacy and safety on insulin glulisine and insulin lispro combined with insulin glargine in patients with Type 1 diabetes. Diabetologia 2004; 47 (Suppl 2): Abstract 835 |
For Type 2 diabetes, evaluation of efficacy was based on an
indirect comparison of results from 2 meta-analyses: (i)
Meta-analysis 1 which compared insulin glulisine and regular human
insulin (Study 3002 to 26 weeks and extension to 52 weeks reported
as study 3012; and separate Study 3005 to 26 weeks) and (ii)
Meta-analysis 2 which compared insulin lispro with regular human
insulin (4 studies).
Studies that compare insulin glulisine with regular human
insulin in the treatment of Type 2 diabetes
| Study | Publication title & citation |
| Study 3002 (week 1-26) | Dailey G et al. (2004) Insulin glulisine provides improved glycaemic control in patients with Type 2 diabetes. Diabetes Care 27(10): 2363-2368 |
| Study 3002 (week 27-52)* | Clinical Study Report only, not published. |
| Study 3005 | Rayman et al (Article in press, corrected proof): Insulin glulisine imparts effective glycaemic control in patients with Type 2 diabetes. Diabetes Research and Clinical Practice (2006), doi:10.1016/j.diabres.2006.09.006 |
* Note that Study 3002 (week 27-52) is not an independent
study.
Studies that compare insulin lispro with regular human
insulin in the treatment of Type 2 diabetes
| Study | Publication title & citation |
| Ross (2001) | Canadian Lispro Study Group A comparative study of insulin lispro and human regular insulin in patients with Type 2 diabetes mellitus and secondary failure of oral hypoglycaemic agents. Clinical and investigative medicine Medicine clinique et experimentale. 24(6):292-8 |
| Anderson (1997) | Improved mealtime treatment of diabetes mellitus using an insulin analogue. Multicenter Insulin Lispro Study Group. Clinical Therapeutics 19(1):62-72 |
| Anderson (1997) | Improved mealtime treatment of diabetes mellitus using an insulin analogue. Multicenter Insulin Lispro Study Group. Clinical Therapeutics 19(1):62-72 |
| Bastyr (2000) | Factors associated with nocturnal hypoglycaemia among patients with type 2 diabetes new to insulin therapy: experience with insulin lispro. Diabetes, Obesity & Metabolism 2(1):39-46 |
8. Results of trials
The results of the key trials are summarised in the table below:
Results of primary efficacy analysis in Study 3001 (week 1- 26)
| Time point | Insulin glulisine group | Insulin lispro group | ||
| n | Mean HbA1c (%) ± sd | n | Mean HbA1c (%) ± sd | |
| Baseline | 331 | 7.60 ± 0.96 | 322 | 7.58 ± 0.89 |
| Week 12 | 301 | 7.51 ± 0.94 | 293 | 7.44 ± 0.87 |
| Week 26 | 279 | 7.42 ± 0.89 | 270 | 7.42 ± 0.92 |
| Endpoint | 331 | 7.46 ± 0.91 | 322 | 7.45 ± 0.92 |
| Mean change from baseline to endpoint ± sd | -0.14 ± 0.709 | -0.13 ± 0.685 | ||
| Adjusted mean change from baseline to endpoint (%) * | -0.14 | -0.14 | ||
| Difference (glulisine - lispro) in adjusted mean (%) ± sd (95% CI) | 0.00 ± 0.949 (-0.09, 0.10) p=0.9329 | |||
n=number of subjects contributing data; sd=standard deviation
* Adjusted means and differences from ANCOVA model
Based on the results from Study 3001 (week 1-26), which compared insulin glulisine
with insulin lispro in Type 1 diabetes, there was no statistically significant difference
between the treatment groups in mean change in HbA1c from baseline to endpoint of
the study.
Similar results were obtained in Meta-analysis 1, which compared the efficacy of insulin
glulisine with regular human insulin (RHI) in Type 2 diabetes, and in Meta-analysis
2, which compared the efficacy of insulin lispro with RHI in Type 2 diabetes.
There was no statistically significant difference between results from Meta-analysis
1 and Meta-analysis 2 in the mean change in HbA1c from baseline to endpoint, which
was cited as evidence of the equivalence of insulin glulisine and insulin lispro in
Type II diabetes.
The data support a lack of difference in rates of hypoglycaemia between glulisine
and regular human insulin.
9. Clinical Claim
The submission claimed that insulin glulisine is no worse than the
comparator (insulin lispro) in terms of effectiveness and toxicity.
The submission claimed that insulin glulisine was non-inferior to
insulin lispro in effecting a mean decrease HbA1c level in Type 1
diabetes and was non-inferior to RHI in Type 2 diabetes.
The PBAC accepted that the non-inferiority of insulin glulisine
compared with insulin lispro in effecting a mean decrease HbA1c had
been adequately demonstrated in both Type 1 and 2 diabetes.
10. Economic analysis
The PBAC agreed that the choice of a cost-minimisation approach was
valid and that the equi-effective doses in this context were
insulin glulisine 100 IU/mL and insulin lispro 100 IU/mL.
A preliminary economic evaluation based on the clinical trial
results was not presented. However, using the average daily dose at
the end-point of the trial in Type 1 diabetes, the cost of
rapid-acting insulin per Type 1 diabetic patient per year is
presented below:
Cost of rapid acting insulin in T1 diabetes per
patient/year
| IU per presentation | ADD * | Scripts per year | DPMQ* $ | Cost of rapid acting insulin per patient/year | |
| Insulin Glulisine | 7,500 IU | 29.47 IU | 1.43 | $262.95 | $376.02 |
| Insulin Lispro | 7,500 IU | 30.68 IU | 1.49 | $262.95 | $391.80 |
* ADD, average daily dose, calculated at the endpoint (52-week) of
Study 3011
11. Estimated PBS Usage and Financial Implications:
The likely script numbers for Type 1 and Type 2 diabetics per year
was estimated to be between 45,000- 75,000 in year 4. The predicted
extra financial cost/saving to the PBS was claimed to be cost
neutral to Government.
12. Recommendation and Reasons:
The PBAC recommended listing as an unrestricted benefit on a
cost-minimisation basis against insulin lispro, with the
equi-effective doses being 1 unit of insulin glulisine and 1 unit
of insulin lispro.
The PBAC accepted that the non-inferiority of insulin glulisine
compared with insulin lispro in effecting a mean decrease HbA1c had
been adequately demonstrated in both Type 1 and 2 diabetes. The
Committee also agreed with the ESC that there is unlikely to be any
clinically important difference in safety between the two
rapid-acting insulins.
Recommendation
INSULIN GLULISINE, injection (human analogue), 100 units per mL, 3
mL, 5
Restriction:Unrestricted benefit
Maximum quantity:5
Repeats:1
13. Context for Decision
The PBAC helps decide whether and, if so, how medicines should be
subsidised in Australia. It considers submissions in this context.
A PBAC decision not to recommend listing or not to recommend
changing a listing does not represent a final PBAC view about the
merits of the medicine. A company can resubmit to the PBAC or seek
independent review of the PBAC decision.
14. Sponsor’s Comment
Sanofi-aventis welcomes the PBAC’s decision to make insulin
glulisine available on the PBS as an unrestricted listing for the
treatment of Type 1 and Type 2 diabetes.
