Download Adlyxin

Adlyxin® - Lixisenatide
Manufacturer: Sanofi
FDA Approval Date: 07/2016
Robert Vincent, PharmD PGY-1
Adlyxin® - Lixisenatide
Objectives
• At the end of this presentation
participants will be able to:
1. Appropriately recommend Adlyxin® (Lixisenatide)
2. Effectively educate patients on the
purpose, proper use and potential
adverse effects of Adlyxin® (Lixisenatide)
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].
Adlyxin® - Lixisenatide
Clinical Application
• Contraindications:
• Hypersensitivity
• Type 1 diabetes
Adlyxin [package insert].
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].
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].
Adlyxin® - Lixisenatide
Drug Facts
• Pharmacology: GLP-1 Receptor
agonist
• Increases glucose-dependent insulin
release
• Decreases glucagon secretion
• Slows gastric emptying
Adlyxin [package insert].
Adlyxin® - Lixisenatide
Drug Facts
• Pharmacokinetics:
A
D
M
Vd≈100L
E
Presumed to be eliminated renally and
through proteolytic degradation. Mean
terminal half-life≈ 3 hours
Tmax 1-3.5 after SQ injection
No significant metabolism
Adlyxin [package insert].
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].
Adlyxin® - Lixisenatide
Adverse Effects
• Adverse Effects: (drug%)[placebo%]
Nausea (25%) [6%]
Vomiting (10%) [2%]
Dizziness (7%) [4%]
Diarrhea (8%) [6%]
Headache (9%) [6%]
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].
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].
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
Cost TBD
Bydureon® - Exenatide
2 mg pen
$692.00 (4 pens)
Tanzeum® - Albiglutide
30/50mg pen
$527.00 (4 pens)
Trulicity® - Dulaglutide
0.75/1.5mg pen
$690.00 (4 pens)
Victoria® - Liraglutide
1.2mg dose pen
$544.00 (2 pens)
Victoria® - Liraglutide
1.8mg dose pen
$831.00 (3 pens)
Lexicomp® Copyright 2016, Wolters Kluwer.
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]
Adlyxin® - Lixisenatide
Literature Review
Results
A1c
Change from baseline
Lixisenatide n=161
Placebo n=162
-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)
Change from
baseline in A1c
-2.70
-1.71
• Significant
reductions
and bodyweight
•
Difference from
NO
difference in
placebo
-1.00
bodyweight (-0.29,
vs. placebo
ALONE
-1.71) p=0.006
Adlyxin [package insert]
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]
Adlyxin® - Lixisenatide
Literature Review
Results
A1c
Lixisenatide n=318 Exenatide n=316
Change from baseline
-0.73
-0.90
Difference from
exenatide
0.17 (0.03-0.31) p=0.0175
Patients achieving
A1c <7%
43.1%
45.6%
Body weight (kg)
Change from baseline
-3.72
• Non-inferiority to exenatide -2.74
(0.4% margin) however,
Differencehad
from significantly greater A1c reduction
exenatide
0.98 No difference?
placebo
Adlyxin [package insert]
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; 373:2247-2257
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; 373:2247-2257
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
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
Adlyxin® - Lixisenatide
References
1. http://www.sanofi.com
2.
Adlyxin® package insert. Sanofi-Aventis. August 2016.
3. Pfeffer, M.A. et al.: Lixisenatide in Patients with Type 2
Diabetes and Acute Coronary Syndrome.
Med 2015; 373:2247-2257
N Engl J