New and Upcoming Treatments for Narcolepsy 2019! Part II Update from World Sleep

Originally at: http://julieflygare.com/new-and-upcoming-treatments-for-narcolepsy-2019-part-ii-update-from-world-sleep/

Did you know the FDA has approved 27 novel drugs so far in 2019, and two of those are for narcolepsy?! How amazing is that?! The diversification of treatment approaches and new therapies under development and gaining FDA-approval for narcolepsy in the U.S. is SO EXCITING!

In this post, I will provide an update on the narcolepsy drug development space and report back highlights from World Sleep 2019. This is Part II, Part I on hypocretin/orexin agonists is here.

Recent FDA Approvals:

 

Solriamfetol/Sunosi

  • Background: Solriamfetol (trade name Sunosi) is a wake-promoting agent, a dual-action dopamine and nonrepinephrine reuptake inhibitor to treat excessive daytime sleepiness in people with narcolepsy and obstructive sleep apnea. Clinical and preclinical data suggested that the wake-promoting effects of solriamfetol differ from medications such as modafinil and amphetamine.
  • Research Findings: Approval of Sunosi was based on data from clinical trials including:
    • One study evaluating excessive sleepiness in adult patients with narcolepsy (TONES 2)
    • Two studies evaluating excessive sleepiness in adult patients with OSA (TONES 3 and TONES 4),
    • An open-label long term safety and maintenance of efficacy for the treatment of excessive sleepiness in patients with narcolepsy or OSA (TONES 5).
  • FDA APPROVAL & Available Now: On March 20, 2019, Jazz Pharmaceuticals announced here that the FDA approved solriamfetol/Sunosi for the treatment of excessive sleepiness in adults with narcolepsy or obstructive sleep apnea. As of July 2019, Sunosi is now commercially available for healthcare professionals and patients in the U.S. 

Pitolisant/Wakix

  • Background: Pitolisant is a histamine H3 receptor inverse agonist that activates histamine neurons, which is an exciting advancement because pitolisant works via a different mechanism of action than any other treatment options currently available for narcolepsy. This article offers some neat ideas about how the treatment may work. 
  • Pitolisant has been on the market in Europe since 2016 when approved by the European Medicines Agency. In Europe, pitolisant is known by its trade name “Wakix”. In October 2017, Harmony Biosciences, LLC acquired the rights to develop, register and market the drug in the United States.
  • Research Findings:
    • At World Sleep 2019: In an oral presentation, Dr. Jeffrey Dayno of Harmony Biosciences shared the results from a study evaluating the abuse potential of pitolisant compared with the stimulant phentermine HCl (C-IV) and placebo in non-dependent, recreational stimulant users. Pitolisant had much lower scores on drug liking compared to phentermine consistent with a lower abuse potential than the more traditional stimulant. Harmony also presented posters further highlighting the efficacy and safety of

Orexin/Hypocretin Agonists are Coming! Part I: Reporting Back from World Sleep 2019

Originally at: http://julieflygare.com/orexin-hypocretin-agonists-are-coming-part-i-reporting-back-from-world-sleep-2019/

Room 116: A Glimpse of the Future

It was a basic, boring conference room, but there was nothing basic or boring about Room 116 at the Vancouver Convention Center on Wednesday, Sept. 25, 2019 at 4:30 p.m. As the final session of the final of five days of the World Sleep Congress including World Narcolepsy Day, I felt wobbly and cataplectic, but I couldn’t go home, not yet. At exactly 4:30 p.m., I eagerly stepped into Room 116 to join narcolepsy experts, drug developers and other patient advocates for a look into the future. 

This final session, simply titled “Narcolepsy” – included researchers sharing important new results related to novel and upcoming narcolepsy therapies. In July 2018, I reported here on the unprecedented amount of drug development underway for narcolepsy. Since then, the FDA has made three important approvals and more drug development continues on, full-steam ahead!

 

So it’s time for an update. Part I will catch you up to speed on orexin/hypocretin agonists, and Part II will share many more exciting developments. 

(Please note: I am not a scientist or doctor. You should always speak with your narcolepsy specialist about treatment options and whether a clinical trial would be a good option for you. However, I hope this post helps provide access to information, because when navigating a complex healthcare system with a serious condition like narcolepsy, information is power.)

Advancing Orexin-Related Therapies

Since 1999, we’ve known that type 1 narcolepsy with cataplexy is caused by a selective loss of neurons producing the neuropeptide orexin (or hypocretin), which plays a central role in maintaining wakefulness. However, finding compounds able to cross the blood-brain barrier and mimic the function of orexin has been scientifically challenging. Over the past 20 years, a few approaches have been explored, but promising research started coming out of Japan a few years ago with Takeda Pharmaceuticals. 

So when Dr. Rebecca Evans took the stage in Room 116 to present Takeda’s first-in-human clinical trial findings for the orexin 2 receptor selective agonist, TAK-925, the excitement was palpable. I felt honored to be in the room as these outcomes were shared publicly for the first time here. 

TAK-925

  • Background: In 2017, a patent for orexin 2 receptor selective agonists, including the clinical candidate TAK-925 was claimed. In April 2018, the orexin 2 receptor-selective agonist, TAK-925, was found to significantly increase wakefulness and recover cataplexy-like episodes in mice with a type of narcolepsy. 
  • A second publication reported on the pharmacological and electrophysiological characterization of TAK-925 from in vitro (petri dish-type studies) and in vivo (studies in wild-type mice, common marmosets, and cynomolgus

Taking a “Sick Day” with Narcolepsy

Originally at: http://julieflygare.com/taking-a-sick-day/

When working in traditional offices, I struggled with “sick days.”

I didn’t often get colds or flus. I just dealt with my narcolepsy with cataplexy, which was fairly stable and “well-managed” by the time I took these jobs.

Yet narcolepsy was still with me every day, to varying degrees — from minor annoyance to extreme discomfort — sprinkled over moments, minutes or hours.

I rarely felt fully “healthy” OR fully “sick” — like bed-ridden, throwing up, or contagious — things deemed worthy of sick days. My more invisible and consistent adversity was hard to measure, hard to explain to a supervisor & hard to decide for myself when to say “Nope, not today.”

I eventually got better at this though and realized I didn’t need to explain myself. I could say “I’m not feeling well enough to work today,” and walk away to do some self-care. (Read here about getting a nap space.)

For the past 1.5 years, I’ve had my dream job working for Project Sleep. Now, I make my own schedule, work at my own pace and do NOT commute three hours a day across Los Angeles.

Interestingly, now that my work is my passion, taking a day off means putting off something I feel strongly about, or delaying something where I feel my “timeliness” reflects upon my leadership skills or my nonprofit’s consistency.

However, by the end of World Sleep, I was zombie-esque and feeling down. Which I realize sounds odd because I had TONS to be happy about after a successful inaugural World Narcolepsy DayWorld Sleep Congress 2019 in Vancouver, Canada. However, I was so depleted & indifferent on my route home on Thursday, I recognized that I needed another full day off.

Yesterday, I unpacked and made a big batch of minestrone soup. I bought three kinds of ice cream and four bunches of flowers and eucalyptus to fill my apartment. I watched YouTube aimlessly, walked lots and lay with my legs up the wall to bring down inflammation in my ankles.

Last night, I started doing my work in my dreams! Today, I’m feeling good enough to get back to this work in reality.

I’m glad I gave my energy wave its due course. Running a non-profit organization as a person with a chronic illness has many interesting dynamics, this is just one of them. I am proud to serve in my role and believe that our organization being run by a person with a sleep condition will serve us well in the long run, so long as I remember to take breaks as needed. Somewhat like choosing …

It’s Almost World Narcolepsy Day, Are You Ready?

Originally at: http://julieflygare.com/its-almost-world-narcolepsy-day-are-you-ready/

The week leading up to World Narcolepsy Day has quickly become one of the most surreal weeks of my life! Seeing posts, articles, videos and radio segments from around the globe honoring World Narcolepsy Day, wow!

World Narcolepsy Day Activities:

I will travel to Vancouver, Canada tomorrow to celebrate World Narcolepsy Day at World Sleep 2019, an international congress on sleep medicine. Join myself and Project Sleep virtually or in-person, here are some opportunities:

World Narcolepsy Day Pronouncement:

Tune in on Sunday, Sept. 22, 2019 at 12:00 noon ET for the World Narcolepsy Day Pronouncement – broadcasting via Facebook Live. Narcolepsy and idiopathic hypersomnia experts and community leaders gathered at World Sleep 2019 will discuss the importance of World Narcolepsy Day, raising awareness and advancing research to improve outcomes for people with narcolepsy and IH around the world.

To watch the live broadcast, simply go to Project Sleep’s Facebook page on Sunday 9/22 at 12noon ET and as soon as we “go live,” the video should show up in our newsfeed!

World Narcolepsy Day #NChat on Twitter

#Nchat is a monthly Twitter conversation that connects people with narcolepsy worldwide. Join in this special #WorldNarcolepsyDay #Nchat on Sunday, Sept. 22nd at 5:00 p.m. ET!

If you’re in the Vancouver area or attending World Sleep 2019, join us in-person for these opportunities:

  • World Narcolepsy Day “Selfie-Station” on Sunday, Sept. 22, 2019 from 10:00 a.m. – 4:00 p.m. PT in the Public Foyer, Vancouver Convention Center
  • Julie Flygare’s Author Table on Sunday, Sept. 22, 2019 from 12:15 – 12:45 p.m. PT in the Public Foyer, Vancouver Convention Center
  • Inaugural World Narcolepsy Day Forum on Sunday, Sept. 22, 2019 from 5:30 – 6:30 p.m. PT in Room 109, Vancouver Convention Center
    • Speakers: Matt O’Neill, Narcolepsy UK, Julie Flygare, JD, Project Sleep, Claire Crisp, Wake Up Narcolepsy, Eveline Honig, MD, Narcolepsy Network, Rebecca King, Hypersomnia Foundation, Mark Patterson, MD, Day4Naps
    • Session description: To mark the inaugural World Narcolepsy Day, Sept 22, 2019, leaders of narcolepsy non-profit patient organizations will share programmatic highlights, best practices and key insights from the front lines. Clinicians, researchers and patient community members will learn about the latest resources from non-profit sector while also fostering new ideas for working together across disciplines to improve outcomes for people with narcolepsy across the world.

GLOBAL begins with LOCAL: 

Awareness begins with one person reaching out to another person in their community. This is why Project Sleep has designed a beautiful World Narcolepsy Day webpage with resources and graphics to help you raise your voice in your community. 

Quick Ways to Support:

  • Add the Facebook Frame: Show support on Facebook by adding the World Narcolepsy Day frame

Living One-Third of My Life with Narcolepsy

Originally at: http://julieflygare.com/living-one-third-of-my-life-with-narcolepsy/

Twelve years ago today, I was diagnosed with a classic case of type 1 narcolepsy with cataplexy, just four days after my 24th birthday. So as of today, four days after my 36th birthday, I’ve now spent one-third of my life officially as a “person with narcolepsy” (not counting the years of symptoms before diagnosis).

For fun today, I searched my emails from that fateful day, Sept 18, 2007, and interestingly, I didn’t mention “narcolepsy” once via email that day, but I did send a lot of writing samples and cover letters for law firm job interviews… Interviews for fancy jobs I would never secure, and visions of “success” I would never realize.

“Futures have a way of falling down in mid-flight.” ~Veronica Shoffstall, After A While

It took a while for me to realize I wasn’t going to “get better and go back to my life as planned” after starting treatment. The emails to my dad proclaiming: “I HATE narcolepsy” started a few months later. For me, the hell of the next several years was a lifetime low.

“Innovation doesn’t happen because there’s some person who’s in some great circumstance and everything is going well and they get on a roll and they make something for the world. Innovation happens—art happens—because of suffering.” ~Claire Wineland, Klick MUSE New York

So here I stand, just four days away from the inaugural World Narcolepsy Day on Sept. 22, 2019. This week, I’m seeing posts from Japan, Australia, Brazil, Myanmar, Argentina, Spain, Finland, the UK, Ireland, and Israel. It’s totally surreal.

This is one of those moments that have made the past one-third of my life the richest years, with lessons learned about pushing beyond my comfort zone, letting go of other people’s expectations, standing up for what i believe in even when its not popular, and finding the courage to build my dream organization Project Sleep to align with like-minded people who want to disrupt the status quo and innovate for a brighter future.

No matter where you are, I want you to know that it is temporary and will not last forever. It’s a bubble. Things will shift or eventually, you can change bubbles. I never could’ve imagined where i would turn up 12 years after my narcolepsy diagnosis, it’s much bigger and more meaningful than anything i ever dreamed for myself.

I never could’ve reached this reality without your support. Thank you to YOUR kindness, trust and love over so many years.❣

from Blog – Julie Flygare http://julieflygare.com/living-one-third-of-my-life-with-narcolepsy/…

Listen: Julie Flygare on Present Not Perfect Podcast in honor of World Narcolepsy Day

Originally at: http://julieflygare.com/listen-julie-flygare-on-present-not-perfect-podcast-in-honor-of-world-narcolepsy-day/

Two people with narcolepsy. Double the insight!

A few minutes into recording, I realized I’d never recorded a podcast with a fellow person with narcolepsy before. This interview with Leyla Sarper for the “Present Not Perfect” podcast was such a neat experience. I’m super excited to share this with you today!

Listen now on Spotify here. Also available on Apple Podcasts, Stitcher, Google Podcasts and more! Just search “Present Not Perfect.”

What did we discuss?

  • being present,
  • letting go of self-guilt,
  • what is sleepiness?
  • coping with invisible illness,
  • Wide Awake and Dreaming: A Memoir of Narcolepsy,
  • cataplexy from Celine Dion,
  • nap rooms at work,
  • awesome dads,
  • building my “no” muscle,
  • learning the world doesn’t revolve around me,
  • re-arranging my life around my passions,
  • finding the courage to START, and
  • and of course, World Narcolepsy Day!!

To listen: Apple Podcasts, Spotify, Stitcher, Google Podcasts and more! Just search “Present Not Perfect.”

I hope you will enjoy and share. Thank you for your support!

from Blog – Julie Flygare http://julieflygare.com/listen-julie-flygare-on-present-not-perfect-podcast-in-honor-of-world-narcolepsy-day/…

Share! Narcolepsy with Cataplexy PSA Video with Ode to Joy Movie

Originally at: http://julieflygare.com/share-narcolepsy-with-cataplexy-psa-video-with-ode-to-joy-movie/

Friends: I’m SO beyond thrilled to share the news with you today that Project Sleep proudly partnered with IFC Films and Ode to Joy Director, Jason Winer, to create a PSA to raise awareness about narcolepsy with cataplexy.

Please watch and share with friends!

Watch this video on YouTube.

Teamwork makes the dream work

I am so grateful to Jason and IFC for their enthusiasm and partnership. Creating this video was a team effort, with significant contributions by many thoughtful people. Most notably, a huge shout out to Hannah Powell for making this project a reality and working with myself and Project Sleep every step of the way!

How this came to be

Over the past year, I researched how other disease communities have worked with and responded to the film industry in similar situations. I interviewed health communications experts and people in “the industry.” I learned A LOT. (Honestly, it would be another post entirely to explain how eye-opening this process was, but I’ll link to my fav articles at the bottom of this post.)

Since Ode to Joy was in post-production as of late 2018, influencing the content of the actual film itself was unlikely. Experts advised me to focus “my asks” on the marketing and distribution phase. 

One of my key “asks” was to collaborate on a short PSA to raise awareness about narcolepsy with cataplexy surrounding the film’s release. Examples I’d seen included Netflix’s To The Bone Nine Truths PSA and The Emoji Movie‘s Stand Up to Bullying campaign.

Once in communication with Ode to Joy’s team, I presented “my asks” and director, Jason Winer, loved the PSA idea and quickly committed to working together to make this happen. This was a surreal moment! I’d spent months researching and formulating my asks, and now it was “go time!”

If you ask for what you want, you better be ready in case you get it!

I had ideas for the PSA and was happy to draft the script, but it was certainly a major undertaking! Jason and I decided to keep this to under one minute. My first draft was around 300 words and the final is about 140 words. I agonized over the pros and cons of each word choice with the help of a few close colleagues and friends.  

About a week before filming, Jason and I agreed that I would join him as “talent” in the PSA. This wasn’t my original plan, but ultimately it made sense, and I liked the idea of a real person with narcolepsy with cataplexy being in the video. 

On the morning …

Are Sleep and Happiness Related? Listen Now To Find Out!

Originally at: http://julieflygare.com/are-sleep-and-happiness-related-listen-now-to-find-out/

I was honored to be a guest on the More Happy Life Podcast with Andy Proctor recently. We talked sleep, spoons, narcolepsy, storytelling, happiness, dreams and more. Listen here.

Episode description: In this episode we talk about all things sleep and much more! How does sleep impact our energy, mood, and clarity? How much sleep do we need each night? How did you discover your narcolepsy? How can we improve our sleep patterns? Should naps be allowed and supported at work? Let’s talk about dreams and remembering dreams. What would you tell people who just found out they have narcolepsy? Find your self affirming voice within all the voices in your head. This will make you happier. 

It was such a joy to share this conversation with Andy and now I’m really enjoying listening to his other More Happy Life podcast episodes too! Listen to our conversation here.

from Blog – Julie Flygare http://julieflygare.com/are-sleep-and-happiness-related-listen-now-to-find-out/…

“Ode to Joy” Movie Review From A Person Living with Narcolepsy with Cataplexy

Originally at: http://julieflygare.com/ode-to-joy-movie-review-from-a-person-living-with-narcolepsy-with-cataplexy/

Today, the new feature film, Ode to Joy opens in select theaters (in New York and Los Angeles) and releases via video on demand across the United States. Ode to Joy is a movie about a man, Charlie (played by Martin Freeman) navigating romance while living with narcolepsy with cataplexy.

I was not involved in the development or filming of this movie, but I’ve been interested since the film was announced in 2011, based on the This American Life segment “I’m Fallen In Love and I Can’t Get Up.” This past April, I attended a showing of Ode to Joy at the Phoenix Film Festival, with Project Sleep board member, Ed Sweet.

As President & CEO of Project Sleep, seeing the film as soon as possible was important to me. Representations of narcolepsy in film provide valuable insight into public perceptions and understanding of the condition. For many individuals, cinematic depictions of narcolepsy may be their only exposure to the symptoms. Thus, patient-driven organizations like Project Sleep, along with narcolepsy advocates and medical professionals, will all benefit from being aware of movie portrayals and joining the conversation as much as possible.

As a person living with narcolepsy with cataplexy myself, I was nervous to see the film. Generally, I close my eyes when clinicians play videos of cataplexy at conferences. Also, I have a short YouTube playlist of other people’s cataplexy episodes and inevitably, tears stream down my face watching these.

Going into seeing the film for the first time, my burning questions were:

1.) How will the movie depict and describe cataplexy? 
2.) How will the movie depict and describe narcolepsy?
3.) How will it depict treatment?
4.) How will it depict the condition’s impact on life? 
5.) Will there be resources exemplified during the film or offered at the end?
6.) Will the film help to raise awareness and/or reduce stigma?
7.) Will I find the movie funny?

Here are my responses. WARNING: from this point on, this post contains spoilers.

1.) How will the movie depict and describe cataplexy?

Physical manifestations: 
I was curious to see how Martin Freeman might act out cataplexy on camera. Cataplexy is such a unique form of muscle weakness/paralysis that can be so sudden and jerky, even I find it hard to “re-enact” on purpose, even having lived with it for over 14 years now.

The physical manifestations of cataplexy in Ode to Joy ranged from accurate (i.e. a knee-buckling and crumbling inward/downward to the ground) to inaccurate (i.e. rigid plank tumbling backward). I would love to know how Freeman prepared for this role – what examples …

Celebrating 20 Years of Hypocretin/Orexin: Narcolepsy’s Big Breakthrough

Originally at: http://julieflygare.com/celebrating-20-years-since-narcolepsys-big-breakthrough-hypocretin-orexin/

LET’S PARTY LIKE IT’S 1999:

Twenty years ago today, a dog named Kahlua was on the cover of the journal Cell. Kahlua was a doberman pinscher with canine narcolepsy and an important piece of history.

Today marks 20 years since Dr. Emmanuel Mignot, MD, PhD, and his team at Stanford University published their key paper in Cell on the genetic mutations responsible for canine narcolepsy. The paper identified that mutations to the hypocretin (orexin) receptor 2 gene caused canine narcolepsy in Kahlua and the Doberman colony at Stanford, a discovery that had important implications for sleep science and humans with narcolepsy.

Mignot’s breakthrough was part of an amazing flurry of scientific discoveries, each building on one another. In 1998, Luis de Lecea, PhD, while at Scripps Research Institute, first discovered that hypocretin existed. Building on this, Mignot’s team published their key paper on August 6, 1999 and just two weeks later, on August 20, 1999, Masasi Yanagisawa and his group at the University of Texas also published in Cell implicating hypocretin (orexin) in mice with narcolepsy-like symptoms.

In Sleepyhead: The Neuroscience of a Good Night’s Sleep, author and fellow person with narcolepsy, Henry Nicholls eloquently tells the riveting history in Chapter 5: Sleeping Dogs Don’t Lie. My summary doesn’t do this story justice, I highly recommend Nicholls’ book!

In 2000, further research suggested that hypocretin was not present in the cerebrospinal fluid of people with narcolepsy. That same year, two groups, Mignot’s team and another led by Jerome Siegel, PhD at UCLA found that the lack of hypocretin in humans with narcolepsy was not due to gene mutations (as was the case with the dogs) but due to hypocretin cells actually being missing in their brains.

So while August 6, 1999 was not the beginning or the end of the hypocretin(orexin) story, it was a huge leap of progress and a moment with celebrating today. This discovery flurry spurred many more questions like: How did hypocretin go missing in the brains of people with narcolepsy? Could targeted treatments be developed to address this deficiency?

1999 – PRESENT:

Recently, I caught up with Dr. Mignot to ask him how he felt about the 20th anniversary of his discovery.

“The ride has been spectacular,” described Dr. Mignot. “From isolation of the hypocretin/orexin receptor gene in dogs, to the autoimmune basis of narcolepsy and the implication of the H1N1 flu as a trigger and now hypocretin/orexin agonists to treat patients, it has never been as exciting.” 

Personally, I wasn’t part of the narcolepsy world in 1999, as I still had my hypocretin. My “grand entrance” came a few