Hetlioz Oral Boards

Vanda Pharma

Hetlioz capsules indications

• Non-24-Hour Sleep-Wake Disorder in adults

• Nighttime Sleep Disturbances in Smith-Magenis Syndrome in patients ages 16 and older

Hetlioz LQ oral suspension indication

Nighttime Sleep Disturbances in Smith-Magenis Syndrome in pediatric patients ages 3-15 years old

Dosage and administration Hetlioz Capsules for Non-24

20mg capsule one hour before bedtime without food at the same time every night

Dosage and administration Hetlioz Capsules for SMS

Patients 16 and older take one 20 mg capsule one hour prior to bedtime

Dosage and administration Hetlioz LQ oral suspension for SMS

For pediatric patients ages 3-15

• ≤28 kg, take 0.7 mg/kg one hour before bedtime

• ≥28 kg, take 20 mg one hour before bedtime

CYP1A2 Interactions

Hetlioz should be avoided in combination with strong CYP1A2 inhibitors because of the increased risk of adverse events.

CYP3A4 Interactions

Hetlioz should be avoided in combination with strong CYP3A4 inducers because of reduced efficacy

Beta-adrenergic receptor antagonists

Nighttime administration of beta-adrenergic receptor antagonists may reduce efficacy of Hetlioz

Hetlioz and smoking

• Smoking is a CYP1A2 inducer

• Hetlioz exposure decreased 40% in smokers compared to non-smokers

• The efficacy of Hetlioz may be reduced in smokers

Top 5 adverse events

• Headaches

• Alanine aminotransferase increase

• Nightmares and abnormal dreams

• Upper respiratory tract infection

• Urinary tract infection

Headaches AE %

17%

Alanine aminotransferase increase AE %

10%

Nightmares and abnormal dreams

10%

Upper respiratory tract infection

7%

Urinary tract infection

also 7%

Contraindications for Hetlioz

NONE

Withdrawal from placebo-controlled studies due to adverse events

6%

Hetlioz and dependence

• Hetlioz does not appear to produce physical dependence

• Discontinuation did not produce withdrawal signs

SET study (Safety and Efficacy of Tasimelteon)

• Study design: randomized, double-masked, placebo-controlled, multicenter

• Patients: 84 patients with non-entrained circadian rhythms randomized to receive Hetlioz or placebo for 26 weeks (42 and 42)

• Primary endpoint: Change from baseline of nighttime total sleeo and daytime nap duration on 25% of the most symptomatic nights and days

• Results: Hetlioz-treated patients had increased 50 minutes of nighttime sleep and daytime nap duration decreased by 49 minutes

  Placebo-treated patients has increased 22 minutes of nighttime sleep and daytime nap duration decreased by 22 minutes

RESET Study (Randomized Withdrawal study of the Efficacy and Safety of Tasimelteon)

• Study design: randomized withdrawal, placebo-controlled study

• Patients: 20 patients with entrained circadian rhythms randomized to receive Hetlioz or placebo for 8 weeks following 12-week open-label Hetlioz treatment

• Primary endpoint: Maintenance of the improvements in nighttime sleep and daytime nap duration following withdrawal.

• Results: Hetlioz-treated patients maintained the benefits (-7 minutes nighttime sleep and -9 minutes daytime nap duration)

  Placebo-treated patients worsened (-74 nighttime sleep and +50 daytime nap duration)

Nighttime Sleep Disturbances in Smith-Magenis Syndrome Study

• Study design: double-blind, placebo-controlled, cross-over study

• Patients: 25 adult and pediatric patients with SMS randomized to two 4-week treatment periods separated by 1-week washout interval (9 weeks total)

• Primary endpoint: Nighttime total sleep (in hours and minutes) and nighttime sleep quality from parent or guardian reported diary

• Results: Hetlioz-treated patients had statistically significant improvement in the 50% worst nights’ sleep quality.

  50% worst nighttime sleep duration numerically favored Hetlioz, but the difference was not statistically significant