FDA Hears Narcolepsy Realities from Patients and Caregivers

By K. Kimberly McCleary

[Access an easily printable/downloadable version of this report: FDA Meeting Summary]

Wake Up Narcolepsy Co-Founder and Executive Director Monica Gow at the FDA on September 24

Wake Up Narcolepsy Co-Founder and Executive Director Monica Gow at the FDA on September 24

The skies above the U.S. Food & Drug Administration’s Silver Spring, Maryland, campus were clear and bright blue, a welcoming sign to nearly 150 narcolepsy patients, family members, and other stakeholders who gathered in the agency’s public facility on September 24, 2013. Many arrived well ahead of the 1 p.m. starting time, making the lobby a hub for greetings between people who’d previously met only online, were renewing long-distance friendships made over the years, or were meeting for the first time. There were nerves to calm and public testimony slots to claim. By the time FDA organizers got the session under way, there were also a few hundred participants logged into the live webcast. The FDA’s fourth Patient Focused Drug Development Initiative meeting and its first on a rare disease broke previous participation records, giving narcolepsy a major spotlight before a large audience that included FDA reviewers, pharmaceutical company representatives, reporters, researchers, advocacy organization leaders, and other government representatives.

Soujanya Giambone of the Office of Strategic Programs in the FDA’s Center for Drug Evaluation and Research (CDER) welcomed the capacity crowd and people watching via the web with an overview of the day. The dozen members of the FDA staff seated at the front tables introduced themselves. Dr. Ellis Unger, director of CDER’s Office of Drug Evaluation I, made opening remarks about the purpose of the meeting and the agency’s efforts to better understand patient perspectives. He acknowledged the serious nature of narcolepsy and continued, “Here at FDA we’re in an ‘ivory tower’ of sorts, a bit isolated from the experience of patients. We’re here to make sure that clinical trials are conducted safely and to approve therapies based on careful analyses of data provided by sponsors. You’re here to shake us up a bit, to help us understand how you experience narcolepsy and view benefits and risks associated with treatment.” Dr. Unger reiterated that it is not within FDA’s mission to test drugs or decide which therapies are to be tested for which conditions, common misunderstandings about the agency’s role. He stated that they want to use information from patients to ensure that clinical trial sponsors focus on symptoms that matter to patients and he invited patients to share what one thing they most want “fixed” about their symptoms or currently available treatments.

Dr. Theresa Mullin describes the FDA's Patient-Focused Drug Development Initiative with FDA colleagues looking on.

Dr. Theresa Mullin describes the FDA’s Patient-Focused Drug Development Initiative with FDA colleagues looking on.

Next, Dr. Theresa Mullin, director of the Office of Strategic Programs, reviewed the purpose of Patient-Focused Drug Development Initiative. “This is a systematic way for us to hear directly from patients that goes beyond the clinical evidence we receive in applications from sponsors,” echoing some of Dr. Unger’s comments. She commended the strong participation from the narcolepsy community in both this meeting and the process that helped FDA staff select the 20 disease areas for this series from 90 conditions nominated through an open comment period held in the fall of 2012. The strong participation of narcolepsy advocates helped propel narcolepsy to the top of the list. She described the prior three meetings on chronic fatigue syndrome (CFS, or ME/CFS), HIV/AIDS, and lung cancer and additions made to the format to expand methods of capturing patient input. Dr. Mullin related how the information being gathered at this session and through the public docket would be used by reviewers, noting that the staff would carefully review all comments and produce a report to be publicly posted as part of the “Voice of the Patient” series. This report series would aid FDA reviewers, drug developers, and sponsors in understanding these clinical areas from the patient’s viewpoint.

Dr. Ronald Farkas, the lead medical officer in FDA’s Division of Neurology Products and chief reviewer for narcolepsy-related applications, provided an overview of narcolepsy and therapies used to treat it. He noted that with a prevalence of 200,000 cases in the U.S., narcolepsy met the agency’s criteria for being a rare or “orphan” disease, a designation that provides various incentives to drug developers. He also noted that there are some 7,000 rare diseases, affecting 1 in 10 Americans. He recognized that narcolepsy can start in childhood, adolescence or later and he reviewed common symptoms and treatments, including the four FDA-approved medications for narcolepsy, cataplexy, or excessive daytime sleepiness – Adderall, Nuvigil, Provigil, and Xyrem.

Ms. Giambone returned to the podium and asked her staff colleagues to distribute the handheld voting devices – nicknamed “clickers” – to people in the audience who identified themselves as patients, caregivers, and family members. She explained that the clickers would be used to elicit and quantify input on questions throughout the afternoon. She also reviewed the two discussion topics that would guide the panelists’ remarks and dialogue with the larger group. Before welcoming the first panel, she conducted five polling questions to capture the characteristics of participants in the room and on the web. Approximately two-thirds of polling participants were people who themselves had been diagnosed with narcolepsy.

panel 1Panel One
The first set of five panelists was then invited to be seated at the head table. This panel was asked to focus on the symptoms they experience and how those symptoms impact their lives. Undergraduate student Kerry Lenzi related her experience with the onset of narcolepsy two years ago and diagnosis in July. She identified the following three symptoms as most disruptive: disturbed sleep cycles, excessive daytime sleepiness and a state of “loopiness” that she described as beginning with hyperactivity, head and neck droop, rapid talking then a blank stare that might occur four times a day. Kerry provided details about how her symptoms impact college class performance and exercise, adding that many of the 25 doctors she’s seen have encouraged her to leave school. Stress, anxiety, being sleep-deprived or dehydrated, sun and heat contributed to symptom flares. She also related several misdiagnoses that preceded her narcolepsy diagnosis, and treatments with serious side effects that she was exposed to before the correct diagnosis was made.

Brandon CoonrodBrandon Coonrod, a composed and articulate 15-year-old high school sophomore, was diagnosed two years ago. Prior to the onset of symptoms he had been a high-achieving student but his inability to stay awake in class led to him being removed from honors classes. Brandon’s most disruptive symptoms included excessive daytime sleepiness, cataplexy, hallucinations (which he described as moving in and out of dreams throughout the day), and automatic behaviors. The greatest impacts on his life are experienced in trying to maintain his performance in school, interacting with friends, the uncertain prospect of driving when he turns 16 and lost opportunity for a future military career. He excused the accusations of fellow students and teachers that his sleep attacks were due to him being lazy or not caring, “It’s not their fault. They don’t understand.” He mentioned the depression that comes along with narcolepsy because of changes in life circumstances and the weight gain that can follow changes in metabolism and activity levels. (See this local news story about Brandon.)

Retired pharmaceutical sales representative Fran Rosen related the sudden onset of sleep paralysis and hallucinations at age 29 that caused her to think she was going crazy. As a single mother, she feared that sharing these symptoms with others would lead to her son being taken from her. Cataplexy came on a few years later when her son would make her laugh, making her think that she was going to have a stroke. The loss of confidence in her abilities as a mother and provider contributed to strong feelings of guilt. In her 40s, the powerful onset of sleep attacks added further challenges to her professional and parenting responsibilities. Finally, at age 49 she picked up a brochure about narcolepsy and recognized the symptoms as her own, leading her to seek medical attention and testing that confirmed the diagnosis. “I had to give narcolepsy control of my life because narcolepsy was winning.” Fran related the misunderstanding and shame she suffered because of an unsympathetic supervisor who did not believe her illness, and ultimately her triumph in being able to perform well in spite of the condition. For Fran, this FDA meeting was her first opportunity to meet another person with narcolepsy in all the years she’s suffered alone.

Panelist Carrie Bollino (center) with her mother (left) and author/blogger Julie Flygare, J.D., the key advocate responsible for getting narcolepsy named to FDA’s list and a leader of the Unite Narcolepsy initiative.

Panelist Carrie Bollino (center) with her mother (left) and author/blogger Julie Flygare, J.D., the key advocate responsible for getting narcolepsy named to FDA’s list and a leader of the Unite Narcolepsy initiative.

Carrie Bollino’s story came next. She paused at the beginning to marvel at how she’d even made it to this day, to this room, given all the times she’d driven in a “daze,” losing up to 30 minutes at a time behind the wheel, but always arriving safely at her destination or parked in a rest area or truck stop. Carrie’s symptoms began in childhood but intensified in college when she had trouble keeping up with studies and socializing with friends the way she wanted to. She described the frightening, dark images that appeared during hynagogic hallucinations and how sleep paralysis attacks dominated her 20s, leading to isolation and depression. She was 39 when the right diagnosis finally helped make sense of these strange, alarming symptoms and she was finally able to dismiss the “lazy” and “unmotivated” labels that had been applied to her by others for so long. Today medications and tight control over her emotions helps her manage her symptoms, although what she described as “irrational eating behavior” is still a problem. She hopes for a brighter future. “I was baited into big decisions of life by low self-esteem, lured by loneliness and depression. Narcolepsy is a darn good trap! I hope being here today can lead to treatments that make the trap disappear for all of us.”

The final panelist for topic one was Joseph Poplawski. He described himself as an “alert zombie” who never feels fully awake. “Daytime sleepiness pervades every moment.” His longest stretch of sleep was 42 hours. He expressed the embarrassment he feels when he falls asleep in public and how every plan he makes includes “a way out.” Cataplexy has come on more recently, as has sleep paralysis. These added symptoms have changed his ability to participate in sports and physical activity with his sons and have contributed to serious weight gain in the last few years. Joe related his challenge with constantly balancing the effectiveness and side effects of medications. He expressed frustration with physicians who are reluctant to write prescriptions for the medications he needs and the judgmental looks he gets from pharmacists who fill the prescriptions. Some of these medications have caused a loss of some of his teeth and he’s ashamed at now having to have others removed. All of these symptoms together have led him to withdraw socially.

symptomsAfter thanking the panel for its courage and honesty, Ms. Giambone proceeded with more polling questions about symptoms to involve participants in the room and on the web. Excessive daytime sleepiness, trouble sleeping through the night, and cataplexy were the most prevalent symptoms among participants in the room and on the web.

These polling questions kicked off a discussion between FDA staff and attendees. The raw emotion of publicly sharing personal struggles was evident; several individuals fought back tears as they offered comments. Author and blogger Julie Flygare, J.D., described the feeling during an attack of cataplexy as “being awake inside a corpse. Am I going to stop breathing? It’s terrorizing. I don’t trust my body because cataplexy can occur at any second.” Monica Gow, co-founder and executive director of Wake Up Narcolepsy, added that doctors didn’t believe her 10-year-old son’s description of cataplexy and only after they videotaped an episode to show doctors did they understand. She described a “popping” sensation that her son feels throughout his body; people around the room nodded in understanding. Another mom and Wake Up Narcolepsy volunteer, Kim Grady, shared how her four-year-old daughter often alerted Kim to her older brother’s cataplexy attacks, a scary event for such a young sibling and the whole family. Another participant related how medical personnel mistook cataplexy for a drug overdose or being drunk. She described a particularly harrowing episode that led to an ambulance driver returning a day later to her hospital room to apologize for not being trained to recognize cataplexy.

Wake Up Narcolepsy volunteer Kim Grady describes the family impact of narcolepsy

Wake Up Narcolepsy volunteer Kim Grady describes the family impact of narcolepsy

Switching to excessive daytime sleepiness, another participant named Michelle explained how her family referred to her sleep attacks as “spells” and still doesn’t understand the condition after many years. She sets dozens of timers around the house and posts notes to remind her about simple, everyday tasks. Many in the room conferred silent agreement with these experiences. Dr. Farkas asked a clarifying question about whether the periods of doing automatic behaviors or blanking out were preceded by a wave of sleepiness. This prompted various answers from participants, demonstrating both common and unique features of patients’ experiences.

A comment from the audience about seasonal variation in symptoms prompted Ms. Giambone to ask for a show of hands of how many people noticed a difference season-to-season; lots of hands went up. Next, in a new addition to the remote participation, FDA staff connected several web participants by telephone. They also summarized comments being posted to the web. “There are hundreds of participants and hundreds of comments being sent; we apologize that we can’t read them all aloud,” a member of the staff team lamented. Forgetfulness, memory loss, constant fatigue, depression, injuries arising from other symptoms, anger, and other mood changes were some of the symptoms raised by those watching via webcast. A short break followed.

Panel Two

As the meeting reconvened, the second panel of patients was invited to take seats at the front table. Ms. Giambone asked panelists to focus on the second topic – current therapeutic options. Allison Greenstein, a physician, described her symptom onset and tools she uses to manage her condition. “Tired. Tired is only feeling I ever knew.” Being in medical school, it took Allison a while before she recognized that her tired wasn’t the same as other people’s tired. Treatment with Provigil had immediate benefit but soon her heart was racing with the slightest activity. A switch to Nuvigil and addition of a cardiac medication has helped balance wakefulness with better heart rate regulation. Allison also credits a gluten-free diet, a regular sleep schedule, regular exercise and a high-quality bed for the modest improvement she experiences. She expressed concern about the high cost of treatment when she briefly found herself without insurance coverage. “I understand now why my patients didn’t take their medications. $500 a month was the difference between keeping the power on and being able to afford medicines.”

Panel 2 allLa Shun Ray, accompanied by her nine-year-old daughter, described the “vicious battle of heart, mind, and body” that her daughter courageously fights. She takes two medications to stay awake and one to sleep at night and still her day is punctuated by the need for regular naps. Medication side effects include headaches, dizziness, weight gain, and suppressed appetite. Her daughter has trouble swallowing the adult-sized pills, even when they’re cut in half. La Shun also described her own deteriorating health in the face of being a full-time caregiver who has to wake each night to administer the second dose of the medication that helps her daughter sleep. She called for studies of medications in children and a better understanding of long-term effects.

For Casey Thompson, a self-employed single mother of four children, Xyrem was a “miracle,” greatly helping reduce cataplexy episodes. Echoing others’ comments about the importance of diet, she offered the suggestion to eat a daily banana to help leg cramps that can be a medication side effect – something she notices if she misses for a day or two. She returned to the topic of seasonal variations, noting that her body “is controlled by the sun.” Casey will use a special light this fall as the days grow shorter, hoping this will help extend wakefulness into evening hours. She ended with a poignant reminder that narcolepsy is no joke – a statement repeated often by people at the meeting and in comments submitted to Unite Narcolepsy’s Patient-Focused Narcolepsy Survey.

treatmentsSharon O’Shaunnessy went 35 years without a proper diagnosis and her treatment is complicated by co-existing conditions including fibromyalgia, Reynaud’s syndrome, allergies, asthma, and GI problems. She longs for a therapy that will address sleep architecture, not simply sedate her. Xyrem had provided one restorative night of sleep from which she awoke refreshed and joyful, but her husband reported an hour-long battle during the night when she had seizure-like movements that he couldn’t stop. The company recommended she stop the medication rather than tweaking the dose. Her current regimen includes frequent naps, Lunesta, Lyrica, Claritin, Norvasc, asthma medication when needed, several supplements, probiotics, regular exercise, and good nutrition (with no processed foods). Her productivity is still unpredictable so she volunteers since she can’t adhere to the “awake” work schedule that society demands.

This was the best-attended meeting of the FDA series so far, with nearly 150 participants on-site and hundreds viewing the webcast.

This was the best-attended meeting of the FDA series so far, with nearly 150 participants on-site and hundreds viewing the webcast.

The final panelist, Justin Greene, spoke slowly and deliberately about his experience with narcolepsy that began in childhood and of “being incapable of participating in his life” until he was treated with medicines approved for narcolepsy. The strategy he uses to maximize his function depends on controlling stress, the season of the year, and managing an increasing tolerance to medications he relies on. He challenged drug developers to start over and test medications under “normal life” conditions to help patients better manage the condition. He proposed that there was unlikely to be a single solution and suggested that treatment be tailored to subtypes such as narcolepsy with and without cataplexy, with and without comorbid conditions. “I’d like to be the last of the children who has no choice but to sleep through a bright future.”

To again engage the wider audience in the dialogue, Ms. Giambone launched a series of polling questions about current therapies. Stimulants including Provigil, Nuvigil, and Adderall had been used by 100% of people in the room and 96% of the people watching by webcast. Xyrem had been used by 72% of people in the room and 66% of people watching via the web. Through comments the use of multiple therapies at one time and over time was highlighted, as was the need for patients to live according to tight dosing schedules that often impacted family and social life and made spontaneity impossible.

The high rate of endorsement of naps by more than 90% of participants led to a discussion during which some resisted the classification of naps as a therapy. Another suggested it was “necessary, not voluntary.” One resisted the classification of naps as therapy when she saw frequent napping as a core symptom of the disease. Kim Grady noted that society was not nap-friendly. Her son was able to take to the SAT with scheduled nap breaks and did very well, but sometimes schools do not permit this flexibility for regular class participation. Another emphasized that timing of naps relies on a complex set of factors that is often unpredictable. Finally, one spouse added that his wife needs two three-hour naps a day which dramatically cuts down on the time she has for other activities.

One of the FDA reviewers asked if antidepressants were used to treat depression or for some other reason. The audience collectively offered that they’re often prescribed to treat cataplexy, to improve sleep, and prevent REM intrusions during the daytime.

Ms. Giambone asked for comments about other downsides to treatments. Dental issues came up often and one participant suggested using Biotin toothpaste and oral spray. Balancing tolerance and addiction were flip sides of a coin raised by web participants. Brain fog was raised by one of the web commenters and came up often in the survey. “Pressed” speech and other speech issues were noted too. Finally, a continual theme was the “zombie-like” state that patients experience. One described uncontrollable eating during the night that she doesn’t remember in the morning. Her family now barricades her in the bedroom at night; she fears what would happen to her if there were a fire in the middle of the night.

Ms. Giambone asked what participants would consider an “ideal” therapy and participants responded with comments about orexin replacement therapy – proposing a kind of “synthroid” for narcolepsy. Several commented about Xyrem’s “wonder drug” properties, but were critical of the high cost and fear they would lose access if their insurance coverage ended. One said she’d be wheelchair-bound without the medication. The need to plan ahead and the dosing schedule were also difficult to maintain. In response to Dr. Mullin’s question about which symptoms patient would most like to address, one longed for a treatment that would provide more wakefulness and eliminate brain fog. Many nodded in accord with this simply stated request. One woman lamented that she had not slept more than two hours in many decades and she wished for a treatment that would allow her to sleep through the night.

Nancy Ackerman shares her experiences.

Nancy Ackerman shares her experiences.

A public comment period allowed nine individuals to offer short statements. Nancy Ackerman conveyed her wish that others would understand that she has “a medical condition, not a character flaw. My life will never be the one I imagined and that’s the hardest pill of all to swallow.” Julie Flygare drew attention to hypnagogic hallucinations and sleep paralysis, symptoms she felt had not received adequate attention. She also admitted to difficulties with mood regulation, especially when waking from a nap. Monica Gow described the challenges of getting her son correctly diagnosed and provided a short history of her co-founding Wake Up Narcolepsy to support research and decrease the time to diagnosis. She also explained the Unite Narcolepsy initiative to prepare the community for this meeting. Next, Kim Grady summarized interim results of the first 1,350 responses to the Unite Narcolepsy survey, many of which mirrored responses to polling questions. Building on earlier comments about the importance of diet issues, Meaghan Doyle described her intense sugar and carbohydrate cravings. She also commented on hallucinations and like others had noted, has trouble distinguishing reality from dreams. Dr. Jed Black, a narcolepsy specialist at Stanford University and consultant to Jazz Pharmaceuticals, commended the FDA and patients on the “remarkable process” of drawing out the patient experience. He validated the profound impact that narcolepsy has on the lives of his patients and admitted that his physician colleagues can be “dense and arrogant” when it comes to topics that are not informed about. He encouraged patients to tell their physicians and the world about the reality of their lives. Dr. Mark Patterson, a pediatrician and father of a patient, who feels educating physicians is one of the biggest issues. He raised concerns about Xyrem because of its strong sedative properties. He also underscored the desperation he sees among patients. Moshe Turner offered his belief that narcolepsy is a neurological condition caused by orexin signaling problems. He described current therapies as “bandaids” and urged attention to the issues of aging with narcolepsy because of the body’s diminishing ability to maintain homeostasis. Patricia Higgins was last to speak. She confided that her long battle with narcolepsy included some very low points at which she contemplated suicide, advocating that more attention be given to treating depression when it occurs.

Dr. Eric Bastings, acting director of the FDA’s division of neurology products, drew the session to a close. He summarized what he had heard that day from patients about their symptoms, the terrorizing nature of the symptoms and fears they provoked. He recounted the huge impact on lives – schooling, choice of career, getting a job, keeping a job, social interactions, friends, family life. Speaking of available treatments, he relayed the wide use of many different drugs, there being no “magic bullet,” that patients still experience significant symptoms in spite of using many treatments, and that side effects and tolerance are huge issues. “A lot remains to be done,” he noted and stated that he heard treatments to improve alertness, brain fog, and allow patients to sleep through the night were needed. He thanked all who participated in the session for attending and participating so fully and thoughtfully and bid everyone safe travels home.

Post-Meeting Activities
Immediately following the meeting, Wake Up Narcolepsy and Unite Narcolepsy invited everyone in attendance to gather for a reception at a nearby hotel. About 40 people made the four-mile trip after the long, emotional afternoon. They shared impressions of the day and experiences from their lives, exchanged coping tips and email addresses. It was a lively gathering, again demonstrating the limited venues that people affected by narcolepsy have to relieve the isolation and silent suffering that misunderstanding and incapacity can impose.

Capitol BuildingThe following day, Monica Gow and Kim Grady of Wake Up Narcolepsy met with staff for four members of Congress representing their home state and districts: Sen. Edward Markey (D-MA); Sen. Elizabeth Warren (D-MA); Rep. John Tierney (D-MA-6); and Rep. McGovern (D-MA-2). They reported on the FDA meeting, research efforts the organization supports at Beth Israel Deaconess/Harvard Medical School in Boston and at other leading institutions, and a program being piloted in Massachusetts to educate school nurses and administrators about narcolepsy, Narcolepsy Goes to School. The reception from staffers was warm and there has already been some follow-up and additional outreach conducted. The blue sky over the Capitol dome was the perfect metaphor for the prospect for better health for all people with narcolepsy, thanks to all who have participated in this FDA effort.


There’s still time to make sure your voice is heard. Here are two ways you can share your experience and perspectives:

  • Complete the Survey: Take 15-20 minutes to respond to the Unite Narcolepsy Patient-Focused Survey based on FDA’s questions and other issues important to narcolepsy patients: https://www.surveymonkey.com/s/unitenarcolepsy All survey responses received by November 15, 2013 will be submitted to FDA before the November 25, 2013 deadline. We will also update the interim summary of the first 1,350 responses with final responses. We’re exploring ways to make the valuable data set available to researchers.
  • Respond to the FDA Docket: We’ve made it easy to provide input directly to FDA. Read the step-by-step instructions here or visit the docket site directly.

Join us on Thursday, Oct. 10 at 2:00 PM (Eastern) time for a final “wrap-up” webinar. We’ll recap what happened at the event, review ways that patients and other stakeholders can offer their perspective to the agency, and look ahead at ways to sustain the positive momentum. Free registration: https://attendee.gotowebinar.com/register/5747469788803640834

Kim McCleary served as a consultant to Wake Up Narcolepsy to create the Unite Narcolepsy initiative in preparation for FDA’s Patient-Focused Drug Development Initiative meeting on narcolepsy. She was also involved in planning the agency’s ME/CFS meeting as former president & CEO of the CFIDS Association of America.