Transcript uptravi

Uptravi® - Selexipag
Manufacturer: Actelion
FDA Approval Date: December 21, 2015
Uptravi® - Selexipag
Objectives
• At the end of this presentation
participants will be able to:
1. Appropriately recommend Uptravi® -
(Selexipag)
2. Effectively educate patients on the
purpose, proper use and potential
adverse effects of Uptravi® - (Selexipag)
Uptravi® - Selexipag
Clinical Application
• Indications:
• Treatment of pulmonary arterial
hypertension (PAH), WHO Group I, to
delay disease progression and reduce
risk of hospitalization for PAH
• Place in therapy:
• As monotherapy or in combination with
other classes of PAH medications
Uptravi® [package insert].
Uptravi® - Selexipag
Clinical Application
• Contraindications:
• None
• Black Box warnings
• None
• Warnings & Precautions:
• If pulmonary edema occurs, consider pulmonary
veno-occlusive disease (PVOD). If PVOD
confirmed, discontinue use of selexipag
Uptravi® [package insert].
Uptravi® - Selexipag
Clinical Application
• Pregnancy:
• No studies in pregnant women
• No relevant clinical effects in animal
reproductive studies
• Lactation:
• Unknown if excreted in human breast
milk
• Recommend discontinuation of selexipag
if nursing
Uptravi® [package insert].
Uptravi® - Selexipag
Drug Facts
• Pharmacology:
• Prostacyclin IP receptor agonist
• Vasodilator
Uptravi® [package insert].
Uptravi® - Selexipag
Drug Facts
• Pharmacokinetics:
A
Time to peak (selexipag): 1-3 hours
Time to peak (metabolite): 3-4 hours
~30% lower Cmax, and delayed time to Tmax in presence of food
D
Highly bound (99%) to plasma proteins
M
Hydrolysis to yield active metabolite, then metabolism
catalyzed by CYP3A4 and CYP2C8
E
Terminal t ½ (selexipag): 0.8-2.5 hours; terminal t ½ (active
metabolite): 6.2-13.5 hours
Uptravi® [package insert].
Uptravi® - Selexipag
Drug Interactions
• Drug Interactions
• Avoid concomitant administration with
strong CYP2C8 inhibitors (e.g.
gemfibrozil) as this results in increased
exposure to selexipag and active
metabolite
Uptravi® [package insert].
Uptravi® - Selexipag
Adverse Effects
• Common Adverse Effects:
(selexipag%)[placebo%]
• Headache (65%) [32%]
• Diarrhea (42%) [18%]
• Jaw pain (26%) [6%]
• Nausea (33%) [18%]
• Serious Adverse Effects:
• none
Uptravi® [package insert].
Uptravi® - Selexipag
Monitoring Parameters
• Efficacy Monitoring:
• 6-minute walk distance
• WHO functional class
• Toxicity Monitoring:
• Unmanageable adverse effects
Uptravi® [package insert].
Uptravi® - Selexipag
Prescription Information
• Dosing:
• Initial: 200 mcg PO BID
• Titration: Increase dose by 200 mcg PO
BID at weekly intervals to maximum
tolerated dose
• Maximum dose: 1600 mcg PO BID
• Cost: – $13,000 per 30 days
Uptravi® [package insert].
Medpagetoday.com 1/6/16
Uptravi® - Selexipag
Griphon study – selexipag for
pulmonary arterial
hypertension
Uptravi® - Selexipag
Literature Review
• Purpose: Efficacy and safety of
selexipag in patients with pulmonary
arterial hypertension who were either:
• Not receiving therapy at baseline or
• Receiving one or two therapies for the
disease at baseline
Sitbon O, et al. N Engl J Med. 2015;373(26):2522-33.
Uptravi® - Selexipag
Literature Review
• Study Design:
• Multi-center, randomized, double-blind,
placebo-controlled, event driven, phase 3
study
• 1156 total patients, 181 centers, 39
countries, December 2009-May 2013
• Treatment arms
• Selexipag
• Placebo
Sitbon O, et al. N Engl J Med. 2015;373(26):2522-33.
Uptravi® - Selexipag
Literature Review
• Inclusion:
• 18-75 years old
• PVR 5 wood units, 6 minute walking
distance (6MWD) 50-450 m
• No treatment for PAH
• Treatment with endothelin receptor
antagonist, PDE5 inhibitor, or both at a
dose stable for at least 3 months
Sitbon O, et al. N Engl J Med. 2015;373(26):2522-33.
Uptravi® - Selexipag
Literature Review
• Primary Endpoint:
• Time to event analysis:
• Composite of death from any cause or
complication related to PAH up to the
end of the treatment period (7 days
after the last intake of selexipag or
placebo)
Sitbon O, et al. N Engl J Med. 2015;373(26):2522-33.
Uptravi® - Selexipag
Literature Review
• Secondary Endpoints:
• Change in 6MWD from baseline to week 26
• Absence of worsening of WHO functional class
from baseline to week 26
• Death due to PAH or hospitalization for
worsening of PAH up to the end of treatment
period and death from any cause up to the end
of the study
• Safety: Adverse effects and lab
abnormalities
Sitbon O, et al. N Engl J Med. 2015;373(26):2522-33.
Uptravi® - Selexipag
Literature Review
Baseline Characteristics
Age
Female
WHO Functional Class III
Average 6 minute walk
distance
Background PAH
treatments
48 years
80%
69%
353 meters
20.4% none
14.7% ERA
32.4% PDE5i
32.5% ERA + PDE5i
Sitbon O, et al. N Engl J Med. 2015;373(26):2522-33.
Uptravi® - Selexipag
Literature Review
• Results:
• 123 patients experienced primary end point
• Side effects with highest risk of discontinuation:
• Headache
• Diarrhea
• Nausea
• More common in dose adjustment phase
Sitbon O, et al. N Engl J Med. 2015;373(26):2522-33.
Uptravi® - Selexipag
Literature Review
Placebo
Selexipag
P-value
41.6
27
<0.001
18.7
13.6
17.2
6.6
23.5
17.8
0.003
- 9.0 m
+ 4.0 m
0.003
74.9
77.8
0.28
Primary Endpoint
All events
Hospitalization for
worsening PAH
Disease progression
Secondary Endpoint
All events
6MWD change from
baseline
No worsening in
WHO functional class
Sitbon O, et al. N Engl J Med. 2015;373(26):2522-33.
Uptravi® - Selexipag
Literature Review
• Conclusions:
• Selexipag lowers rate of death or
complication related to PAH vs. placebo
• No difference in mortality between
groups
• Addition of selexipag to baseline regimen
of two meds gave benefits consistent
with overall treatment effect
• Similar efficacy regardless of dose range
Sitbon O, et al. N Engl J Med. 2015;373(26):2522-33.
Uptravi® - Selexipag
Summary
• Uptravi®, Selexipag, is an oral prostacyclin receptor
agonist for pulmonary arterial hypertension (PAH)
• Should not be used with strong CYP2C8 inhibitors
• Administered at 200 mcg BID and titrated on a weekly
basis to the highest tolerated dose or the max dose of
1600 mcg BID
• Most common side effects include; headache,
diarrhea, jaw pain and nausea
• Can use in combination with PAH medications (PDE-5
inhibitors and endothelin receptor antagonists) but
should not be used with another prostacyclin agonist
Uptravi® - Selexipag
References
1. www.uptravi.com
2. Uptravi package insert. Actelion. Dec. 2015.
3. Sitbon O, Channick R, Chin KM, et al. Selexipag
for the Treatment of Pulmonary Arterial
Hypertension. N Engl J Med. 2015;373(26):2522-33.