1. P & T Committee Formulary Review Exubera® Insulin Human (rDNA origin) Inhalation Powder
Elena Chan PharmD Candidate UCSF
Tiffany Jew PharmD, MBA Candidate USC
Pro Pharma Pharmaceutical Consultants, Inc

2. Outline Overview of P&T Committee Formulary Submission Dossier
Exubera® – Inhaled Insulin
Prior Authorization Criteria

3. Pharmacy and Therapeutics (P&T) Committee
The role of the P&T Committee:
Objectively appraises, evaluates, and selects drugs for formulary – value, place in therapy, and impact on budget
Manages formulary in light of new drugs, indications, and warnings
Develop policies for educating and informing providers about new drugs and committee decisions
Quality improvement
Develop generic substitution and therapeutic interchange programs
Develop procedures for use and access to non-formulary drugs
Committee meets regularly throughout the year
Members include physicians, pharmacists, administrators, and other health care professionals

4. Formulary Submission Dossier

5. Overview of Diabetes Diabetes total U.S. prevalence in 2005
20.8 million people (7% of the population)
Type 1: 5-10% of diagnosed cases
Type 2: 90-95% of diagnosed cases
Gestational: 20-50% of those will go on to have Type 2 in the next 5-10yrs
Medications used by diabetics:
57% Oral medications only
16% Insulin only
12% Insulin + Oral medications
15% None
Direct and indirect costs = $132 billion in 2002
Risk factors for diabetes: genetic, sedentary lifestyle, overweight, pre-diabetes
14.6 M are diagnosed
Type1: pancreas unable to produce insulin
Type 2: poor diet and exercise and other factors prevent the body from sensing insulin as well as it used to
Gestational: elevated glucose levels during pregnancy that may or may not resolve
Pre-diabetes – lots of in
Talk about measures of glycemic control (A1C, blood glucose measures). When glycemic control is not achieved then you increase the risk of complications – kidney disease, peripheral neuropathy, retinopathy; hospitalizations/doctor visits
CDC National Diabetes Fact Sheet 2005

6. Product Information
Exubera® is a dry powder formulation of recombinant human regular insulin that is administered via oral inhalation
Indication: Diabetes mellitus type 1 and 2
Forms: Comes as 1mg or 3mg blister packs
Dose:
Determined from preexisting premeal insulin or by weight
Administer 2-4 times/day 10min before meals

7. Pharmacology Human insulin produced by recombinant DNA technology
Insulin regulates glucose metabolism by stimulating uptake of glucose from the blood into skeletal muscle and fat and inhibiting hepatic glucose production.

8. Pharmacokinetics Exubera® SubQ Regular Insulin
After inhalation, insulin is rapidly absorbed across the pulmonary epithelium
Mean time to peak serum concentration = 45minutes
Bioavailability:
4.9-11% for nonsmokers
12-19% for smokers

9. Pharmacodynamics Onset of action = 10-20 min (similar to
rapid-acting insulins)
Duration of action =
6 hrs (similar to regular)
PD/PK differences exist
among respiratory
diseases.
More absorption in patients with COPD and smokers
Less absorption in mild asthma
No differences found between age, sex, pregnancy
Exubera® Package Insert.
Clinical Pharmacology accessed Mar 2007

10. Warnings and Interactions
Contraindications:
Hypersensitivity to Exubera®/any of its excipients
Smokers/ex-smokers<6months
Poorly controlled lung disease
Adverse Reactions:
Hypoglycemia, chest pain, dry mouth, otitis media in peds
Cough, dyspnea, pharnygitis, sputum, epistaxis, decrease in pulmonary function (FEV1)
Common Drug Interactions:
Reduce insulin’s effect: corticosteroids, diuretics, sympathomimetics, glucagon, estrogens/progesterone, protease inhibitors, atypical antipsychotics, thyroid hormones
Increase insulin’s effect: oral antidiabetics, ACE-I, fibrates, fluoxetine, MAOI’s
Mask the symptoms of hypoglycemia: b-blockers, clonidine
Affects absorption- leading to hypo- or hyperglycemia

11. Place in Therapy Manufacturer Recommendations:
Type 1: use in combo with longer-acting insulin
Type 2: use as monotherapy or with oral diabetic meds or longer-acting insulin
Effective in patients poorly controlled on oral hypoglycemics or insulin
May be useful for patients who prefer inhaled over injected route for their rapid-acting insulin
American Diabetes Association Recommends:
Inhaled insulin not included in treatment algorithm
Statements on the ADA website question the long-term safety and cost-effectiveness of inhaled insulin
Other published guidelines question the efficacy of inhaled insulin in lowering A1C<7%

12. Treatment Algorithm for Type 2 Diabetes

13. Submission of Clinical Trials
The manufacturer should include:
All pivotal clinical and economic studies – published and unpublished
Spreadsheet or table of these trials
Major conclusions from Cochrane/Agency for Health Research and Quality
Allows the P&T Committee to practice “evidence-based medicine”
Evaluate quality, strength of clinical trials
Weigh out risks and benefits of drug, including no treatment
According to the Centre for Evidence-Based Medicine, "Evidence-based medicine is the conscientious, explicit and judicious use of current best evidence in making decisions about the care of individual patients.

14. Submission of Cost-Effectiveness Models
Why do we need one?
Projects the value of the product taking into account both efficacy and cost
How the addition of the product will affect the health plan’s formulary
Determines the product’s place in therapy in the formulary
Compares the product to “gold standards”
What should one include?
Take into account absolute and relative risk reductions, costs associated with administering this drug and its potential adverse effects
Assumptions and calculations should be reasonable and accurate

15. Statement of Product Value
Allows manufacturer to communicate value of product
Summarize clinical and economic data
Estimate the per unit product cost
Example:
“Inhaled insulin was demonstrated to have similar efficacy and side effects as injectable regular insulin, but patients prefer inhaled to injected. It may improve quality of life and reduce diabetic complications in those patients that are resistant or non-adherent to injectable insulin. Although it may cost more, it may generate savings if patients achieve better glycemic control due to better compliance to insulin therapy. ”

16. Cost Comparison Table Regular Insulin (12,775 Units/year) Exubera®
1mg of Exubera® = 3 IU of Regular SC Insulin
Release unit needs to be replaced every 2 weeks
Cost comparison of a 70kg adult using 0.5 Units of regular insulin/kg/day
Costs are calculated over a year of use
Based on AWP
Regular Insulin
(12,775 Units/year)
Exubera®
(4,380 mg/year)
Syringes = $221.40
Insulin vials = $787
$1008
1 chamber= $19
28 release units/year = $84
Blister packs = $3042
$3145 + +

17. PA Criteria Patients must be: For Type 1 Diabetics:
18 years or older with a diagnosis of diabetes type 1 or 2
Non-smokers
No hx of COPD, asthma, or other chronic respiratory disease
Documented A1C> 7% and baseline pulmonary function test
For Type 1 Diabetics:
Must be used with a long-acting insulin (cannot use Exubera® as monotherapy)
Patient has a need for short-acting insulin to achieve glycemic control
AND patient has difficulty with performing multiple injections (disability, blind)

18. PA Criteria Continued For Type 2 Diabetics:
First, must have tried and failed to achieve glycemic control w/ max doses of oral agents or are contraindicated
Then, must have tried to achieve glycemic control w/ a full injectable insulin regimen (long-acting + short-acting)
AND patient has difficulty with performing multiple injections (disability, blind)
Exubera® must be used in combination with a long-acting insulin and oral agents (unless contraindicated)

19. Questions?