Jazz Pharmaceuticals

Narcolepsy Overview

According to the National Sleep Foundation, Narcolepsy “is a sleep disorder characterized by excessive
sleepiness, sleep paralysis, hallucinations, and in some episodes of cataplexy (partial or total loss of
muscle control, often triggered by strong emotions such as laughter). Narcolepsy occurs equally in men
and women and is thought to affect roughly 1 in 2,000 people. The symptoms appear in childhood or
adolescence, but many people have symptoms or narcolepsy for years before getting a proper diagnosis.”

People with narcolepsy experience sleep paralysis and hallucinations when falling asleep or waking up.
Sleep paralysis coupled with hallucinations can be frightening for those with narcolepsy.

Narcolepsy symptoms vary but first appear between the ages of 7 and 25. Most patients experience
difficulty sleeping at night and have difficulty functioning at school, work, home and social situations
(National Heart, Lung and Blood Institute).There is no cure for narcolepsy but drug therapies and lifestyle
changes can improve quality of life and minimize symptoms. There are five drug treatments approved to
treat patients: Xyrem, Provigil, Nuvigil, methylphenidate, and amphetamine.

Xyrem is a central nervous system depressant. It is used reduce the symptoms of patients with cataplexy
and excessive daytime sleepiness. In some cases Xyrem can slow or stop breathing, even if the patient is
taking the prescribed dosage. Xyrem is also known as GHB, a street drug known for being abused, for this
reason Xyrem is only available from a certified pharmacy under a special program called Xyrem REMS
Program. The doctor prescribing Xyrem must also be registered in the program in order to prescribe Xyrem
to a patient.

Provigil (modafinil) promotes wakefulness by altering the neurotransmitters in the brain. Provigil is often
prescribed to patients that have, sleep apnea and narcolepsy. If a patient is allergic to modafilin or Nuvigil
they will most likely get a skin rash from taking Provigil.

Nuvigil (armodafinil) promotes wakefulness and is used to treat excessive sleepiness caused by sleep
apnea, narcolepsy and shift work sleep disorder. If a patient is allergic to Provigil they will most likely get a
skin rash from Nuvigil.

Methylphenidate is a central nervous system stimulant. It affects the nerves and chemicals in the brain
that contribute to hyperactivity and impulse control. Methylphenidate is prescribed to those with attention
deficit disorder (ADD), attention deficit hyperactivity disorder (ADHD), and narcolepsy. Methylphenidate is
habit-forming drug and should not be prescribed to patients who have had drug or alcohol abuse problems.
Stimulants have caused stroke, heart attack, and death in patients with high blood pressure, heart disease
or a heart defect.

Amphetamine is a central nervous system stimulant. It affects chemicals and nerves in the brain that
contribute to impulse control and hyperactivity. Amphetamine is used to treat patients with attention
deficit hyperactivity disorder (ADHD), narcolepsy and occasionally obesity in people who have not lost
weight with diets or other treatments. Amphetamine can be habit forming and should not be prescribed to
patients who have had drug or alcohol abuse in the past. It is a stimulant so it can cause strokes, heart
attacks, or sudden death in patients with high blood pressure, heart disease, or a heart defect.
Amphetamine is not recommended to anyone with an overactive thyroid or severe anxiety.

Doctors often prescribe Provigil or Nuvigil to patients first because it isn’t as addictive as older stimulants
and doesn’t give patients the highs and lows that other stimulates do. Some patients need to be treated
with methylphenidate or other amphetamines, however these medications can have extreme side effects
(nervousness, heart palpitations, and addiction).

Types of Narcolepsy:
Clinicians recognize two major types of narcolepsy: narcolepsy with cataplexy (often referred to as
narcolepsy type one) and narcolepsy without cataplexy (often referred to as narcolepsy type two).Those
who have narcolepsy without cataplexy have generally less severe symptoms. Type two accounts for
approximately 30% of people diagnosed with narcolepsy.

Excessive Daytime Sleepiness (EDS): A neurological disorder in which there is a sudden recurrent
uncontrollable compulsion to sleep. Roughly 20 percent of the population can be classified as having
excessive sleepiness.

Patients are diagnosed with EDS based on the results of a multiple sleep latency test (MSLT). An MSLT is
when a patient goes to a sleep center and have scheduled naps at two-hour intervals throughout the day.
These consist of 20-minute periods where the patient is put to bed and allowed to lie there with the goal of
falling asleep so technicians can monitor when REM sleep begins. In a patient with narcolepsy REM will
start within 15 minutes of them falling asleep. People who do not have narcolepsy will enter rem 90
minutes after falling asleep.

Cataplexy: Is a debilitating condition in which a person suddenly feels weak and collapses at times of
strong emotion such as during laughter, anger, fear, or surprise. It is a sudden temporary loss of muscle
control. Difference between a seizure and cataplexy is that a seizure can occur at any time and is not
primarily triggered by periods of strong emotion.

Cataplexy rarely occurs in patients who do not have narcolepsy. Cataplexy is worsened when a patient is
fatigued. It may also occur after a patient abruptly stops taking antidepressant medication. Sometimes it
can be seen in other medical conditions including: stroke, multiple sclerosis, head injury and encephalitis.

The diagnosis is based on the patient’s description of events and history. Cataplexy affects males and
females equally. When people with cataplexy collapse they may injure themselves. It’s not a life-
threatening condition unless you experience an attack while engaging in a potentially dangerous activity,
such as operating a motor vehicle or heavy machinery.

o It is recommended that people with cataplexy practice good sleep hygiene:

 Keeping a consistent sleep schedule
 Striving for at least 7 hours of sleep
 Making your bedroom quiet and relaxing
 Limiting exposure to light in the evenings
 Exercising regularly
 Healthy diet
 Avoiding a large meal before bedtime
 Avoiding alcohol
 Scheduling one of more short naps during the day

 To help avoid injury during cataplexy episodes:

 Asses and be aware of potential dangers such as glass, heights, sharp edges
 Avoid sleep deprivation
 Stress management techniques
 Do not drive a car or operate heavy machinery
 Enlist help from friends or significant others

Symptoms:

Excessive Daytime Sleepiness (EDS):

 All individuals with narcolepsy have EDS

 Most obvious symptom
 EDS is characterized by persistent sleepiness regardless of how much sleep an individual
gets at night
 Sleepiness in narcolepsy is more like a “sleep attack”
 In between sleep attacks, individuals have normal levels of alertness, especially if doing
activities that keep their attention
 Cataplexy:

 Facial twitching, flickering, or grimacing

 Unusual tongue movements
 Jaw tremor
 Head or jaw dropping
 Knee trembling or buckling
 Drooping eyelid
 Speech difficulty

Advocacy Groups:

Narcolepsy Network is a non-profit organization dedicated to individuals with narcolepsy and related sleep
disorders. Their mission is “to provide services to educate, advocate, support, and improve awareness of
this neurological sleep disorder.”

Family Shade is a patient support organization. The group’s mission: is to educate and inform individuals
with narcolepsy about their sleep disorder, available treatments, and symptom management. Family Shade
provides emotional support and resources to family members, patients and friends, while also serving as a
resource center for patients, medical providers, educators, employers, and members of the public. Family
Shade also advocates for the interests of all people who have narcolepsy.

An organization called Wake Up Narcolepsy runs and promotes programs like Narcolepsy Education Day.
Wake Up Narcolepsy is a not-for-profit organization dedicated to supporting Narcolepsy awareness and
research to find a cure. They also alert the public of ongoing clinical trials and research.

Support Groups:

There are online resource lists to connect those with narcolepsy to support groups in their state. There is
also a website called Meetup connects people who have narcolepsy.

Many online forums are available for people to pose questions and get answers. One popular online
support group is Living with Narcolepsy. Here people can post discussion questions. Another online support
group is Daily Strength. It has almost 500 members and almost 3,000 posts.

Project Sleep: connects promotes a Facebook Support Group, Twitter chats and a Narcolepsy Advocacy
Center app. Narcolepsy Advocacy Center is the first app for narcolepsy (Project Sleep Facebook).

Recent Media Coverage:

 Medscape: New Drug for Narcolepsy, Sleep Apnea on the Horizon (June 12, 2018)
 Sleep Review: A Biopharma Company Explains Why Histamine Matters in Narcolepsy (June 12,
2018)
 Rare Disease Report: Narcolepsy Treatment Receives FDA Fast Track Designation (May 21, 2018)
 Fox 4: Sleepiness Could Be Narcolepsy (May 24, 2018)
 First News 24: Global Non Cataplexy Narcolepsy Drugs Market 2018 Jazz Pharmaceuticals, Teva
Pharmaceuticals, Novartis, Mylan (June 1, 2018)
 Market Insider: Jazz Pharmaceuticals Presents Long-Term Safety and Efficacy Data from Phase 3
Tones 5 Study of Solriamfetol for Excessive Sleepiness in Narcolepsy of Obstructive Sleep Apnea
(June 3, 2018)
 The New York Times: Patient Voices (March 20, 2018)
 The Guardian: ‘Narcolepsy isn’t funny’ Living with a sleep disorder (Feb 24, 2018)
 Glamour: I’m 27 and Living With Narcolepsy—and It’s Not A Joke (Feb 15, 2018)

More Information:

 The sleep you get when you take sleeping pills is of a lower quality than what you get when you fall
asleep on your own.
 Using devices that emit blue light such as computers, cellphones, etc. especially within few hours of
going to bed can negatively affect sleep.
 Taking long naps, especially in the afternoon and evening. A naptime of 30 minutes or less is best if
you don’t want to negatively impact your sleep.
 Working out before bed. Exercising late in the afternoon or right before going to bed makes it
difficult to sleep well. Exercise raises the heart rate and causes adrenaline to surge through the
system, which can both impact sleep quality.
 Hypocretin levels are particularly low in those who experience cataplexy
o Hypocretins are “neurotransmitters that normally promote stable wakefulness and help
regulate REM sleep.” People who have narcolepsy with cataplexy have a loss of neurons that
produce hypocretins.
o Hypocretins are also referred to as orexins
 People who have narcolepsy have mixed signals sent from their brain about when to sleep which is
why narcoleptics fall asleep at inopportune times.