1. Adlyxin® - Lixisenatide
Manufacturer: Sanofi
FDA Approval Date: 07/2016
Robert Vincent, PharmD PGY-1

2. Adlyxin® - Lixisenatide Objectives
At the end of this presentation participants will be able to:
Appropriately recommend Adlyxin® - (Lixisenatide)
Effectively educate patients on the purpose, proper use and potential adverse effects of Adlyxin® - (Lixisenatide)

3. Adlyxin® - Lixisenatide Clinical Application
Indications:
FDA Approved: Adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes
Potential off-label use: Weight loss
Place in therapy:
5th-in-class GLP-1 agonist without any currently known benefits over other agents in class
Adlyxin [package insert].

4. Adlyxin® - Lixisenatide Clinical Application
Contraindications:
Hypersensitivity
Type 1 diabetes
Adlyxin [package insert].

5. Adlyxin® - Lixisenatide Clinical Application
Precautions
Anaphylaxis and severe hypersensitivity reactions
Acute pancreatitis- discontinue if suspected; do not restart if confirmed. Avoid with history of pancreatitis
Acute kidney injury- monitor renal function with renal impairment reporting severe GI reactions. Avoid in ESRD
Gastroparesis- avoid use
Hypoglycemia with concomitant use of sulfonylurea or basal insulin- consider dose reduction of basal insulin or sulfonylurea
Immunogenicity- patients may develop antibodies to lixisenatide
Adlyxin [package insert].

6. Adlyxin® - Lixisenatide Clinical Application
Animal Toxicology:
Thyroid C-cell tumor in rats (all doses)
Pregnancy:
Category C- Limited data in pregnant women. May be risks to fetus from exposure based on animal reproductive studies
Lactation:
No information regarding presence in human milk. Present in rat milk (9.4% transfer)
Adlyxin [package insert].

7. Adlyxin® - Lixisenatide Drug Facts
Pharmacology: GLP-1 Receptor agonist
Increases glucose-dependent insulin release
Decreases glucagon secretion
Slows gastric emptying
Adlyxin [package insert].

8. Adlyxin® - Lixisenatide Drug Facts
Pharmacokinetics: A
Tmax after SQ injection D
Vd≈100L M
No significant metabolism E
terminal half-life≈ 3 hours
Adlyxin [package insert].

9. Adlyxin® - Lixisenatide Drug Interactions
Drug Interactions – Object Drugs:
Due to delayed gastric emptying, drug may impact absorption or orally administered medications (e.g. concentration-dependent antibiotics, narrow therapeutic index drugs, oral contraceptives)
Advise patient to take these drugs 1 hour prior to injection or 11 hours post injection
Adlyxin [package insert].

10. Adlyxin® - Lixisenatide Adverse Effects
Adverse Effects: (drug%)[placebo%]
Nausea (25%) [6%] Diarrhea (8%) [6%]
Vomiting (10%) [2%] Headache (9%) [6%]
Dizziness (7%) [4%] Injection site rxn (4%) [2%]
Hypersensitivity (0.4%) [0.2%]
Hypoglycemia-basal ± SU (47%) [22%]
Pancreatitis (21 per 10,000 pt years) [14 per 10,000 pt years]
Adlyxin [package insert].

11. Adlyxin® - Lixisenatide Monitoring Parameters
Efficacy Monitoring:
Average A1c reduction ≈ 0.8%-1.2%
Toxicity Monitoring:
GI-related symptoms (N/V/D) especially with reduced kidney function
Adlyxin [package insert].

12. Adlyxin® - Lixisenatide Prescription Information
Dosing:
Initial: 10 mcg once daily x 14 days 1 hour prior to first meal
Maint/Max: 20 mcg once daily 1 hour prior to first meal
Brand - Generic
Doses
$ 30-day supply
Adlyxin® - Lixisenatide
10 mcg pen
Cost TBD
20 mcg pen
Bydureon® - Exenatide
2 mg pen
$ (4 pens)
Tanzeum® - Albiglutide
30/50mg pen
$ (4 pens)
Trulicity® - Dulaglutide
0.75/1.5mg pen
$ (4 pens)
Victoria® - Liraglutide
1.2mg dose pen
$ (2 pens)
1.8mg dose pen
$ (3 pens)
Lexicomp® Copyright 2016, Wolters Kluwer.

13. Adlyxin® - Lixisenatide Literature Review
24 week study (n=323) with T2DM inadequately controlled with diet/exercise and metformin alone
Intervention
Lixisenatide 20mcg or placebo in addition to metformin ± SU
Baseline
-56.7 years old
Characteristics
-5.9 years from Dx
(Mean)
-A1c 8%
-BMI 33 kg/m2 (89 kg)
-1,955 mg metformin daily
-90% CrCl > 60 mL/min
Adlyxin [package insert]

14. Adlyxin® - Lixisenatide Literature Review
Results
A1c
Lixisenatide n=161
Placebo n=162
Change from baseline
-0.72
-0.26
Difference from
placebo
-0.46
(-0.64, -0.28) p<0.0001
Patients achieving A1c <7%
44%
22%
Body weight (kg)
-2.70
-1.71
Difference from placebo
-1.00
(-0.29, -1.71) p=0.006
Significant reductions in A1c and bodyweight
NO difference in bodyweight vs. placebo ALONE
Adlyxin [package insert]

15. Adlyxin® - Lixisenatide Literature Review
24 week open label study (n=634) with T2DM inadequately controlled with diet/exercise and metformin alone
Intervention
Lixisenatide 20mcg or exenatide 10mcg BID in addition to metformin
Baseline
-57.4 years old
Characteristics
-6.8 years from Dx
(Mean)
-A1c 7.96%
-BMI 34 kg/m2 (95 kg)
-2,039 mg metformin daily
-90% CrCl > 60 mL/min
Adlyxin [package insert]

16. Adlyxin® - Lixisenatide Literature Review
Results
A1c
Lixisenatide n=318
Exenatide n=316
Change from baseline
-0.73
-0.90
Difference from
exenatide
0.17 ( ) p=0.0175
Patients achieving A1c <7%
43.1%
45.6%
Body weight (kg)
-2.74
-3.72
Difference from placebo
0.98 No difference?
Non-inferiority to exenatide (0.4% margin) however, exenatide had significantly greater A1c reduction
Adlyxin [package insert]

17. Adlyxin® - Lixisenatide Literature Review
Lixisenatide in Patients with T2DM and ACS: ELIXA Study
6,068 patients with T2DM and ACS with past 6 months
Maximum tolerated dose of Adlyxin vs. placebo
Pfeffer, M.A., et al. N Engl J Med 2015; 373:

18. Adlyxin® - Lixisenatide Literature Review
Primary Composite Endpoint of CV death, non-fatal MI, non-fatal stroke, or hospitalization or unstable angina
No difference from placebo in regard to cardiovascular outcomes
Pfeffer, M.A., et al. N Engl J Med 2015; 373:

19. Adlyxin® - Lixisenatide Summary
New once daily GLP-1 agonist indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes
Starting dose of 10 mcg daily x 14 days with a maintenance dose of 20 mcg daily
Dose NTI drugs, conc.- dependent ABX, and oral contraceptives 1 hour before or 11 hours after injection

20. Adlyxin® - Lixisenatide Summary
Most common side effects are GI-related (N/V/D)
Reduce dose of insulin or SU’s when initiating lixisenatide
Avoid ESRD, gastroparesis, history of pancreatitis, or history of thyroid tumors
Likely no better than others in class

21. Adlyxin® - Lixisenatide References
Adlyxin® package insert. Sanofi-Aventis. August 2016.
Pfeffer, M.A. et al.: Lixisenatide in Patients with Type 2 Diabetes and Acute Coronary Syndrome. N Engl J Med 2015; 373: