"This could be my last SLEEP meeting before an orexin agonist hits the market..."

Last week (June 7-11, 2025) in Seattle, I was honored to help represent Project Sleep at SLEEP 2025, the annual meeting of the American Academy of Sleep Medicine and Sleep Research Society.

Bright and early on Wed. June 11th at 8:00 a.m., the session I was most looking forward to took place, "Advances in the Development of Orexin Agonists" chaired by Dr. Thomas Scammell. Three leading orexin agonist developers, Takeda, Alkermes, and Centessa Pharmaceuticals, all provided exciting updates from phase 1 and 2 clinical trials.

On my way home after the meeting, if occurred to me:

"This could be my last SLEEP meeting before an orexin agonist hits the market."

Since then, I keep thinking of all my potential "lasts" this year before an orexin agonist crosses the finish line to gain FDA approval (fingers crossed). Perhaps it's my last birthday, my last World Sleep meeting, my last Holidays... before an orexin agonist reaches the market in the U.S. (and hopefully other countries too).

Maybe this sounds dramatic, but this gives me great hope. While I do not believe orexin agonists will be a "cure" for my type 1 narcolepsy with cataplexy, I do believe this progress represents a historic and major advancement in therapeutic options for people with narcolepsy.

We've come so far!

Not long after my diagnosis, in 2008, an article in the New York Times described how the 1999 discovery of hypocretin/orexin should lead to better treatment options for people with narcolepsy soon, however, “[u]ltimately, experts say, the main obstacle to developing any narcolepsy medication is that the number of patients is too small to lure pharmaceutical firms into making the expensive investment required to bring a remedy to market.”[1]

The article upset and inspired me to study the Orphan Drug Act (ODA) in law school, to better understand the financial incentives in place to encourage rare disease drug development. At the time, it seemed that larger pharmaceutical companies still saw orphan drug development as risky and unprofitable. As a result, large pharmaceutical companies were not often entering the rare disease market, with only 10 percent of all applications for orphan drug designation filed by large pharmaceutical companies.[2] 

Smaller pharmaceutical and start-up companies were developing and marketing orphan drugs with variable success.  However, it seemed advantageous to involve larger companies as well. Larger pharmaceutical companies have more financial security and are in a better position to “sink” the development costs of any one drug.  Small or startup pharmaceutical companies take large risks when investing in any one drug, especially an orphan drug developed and approved for a small patient population.  It is foreseeable that when smaller companies rely on the sales of an orphan drug to sustain an entire business, there will be pressure to expand the drug’s use beyond the limited orphan disease population indication.  Developers of orphan drugs should not have to hope for a lucky "windfall" of finding more widespread uses in order to break even.     

My research led me to conclude that the incentive package of the ODA should be re-examined to encourage larger pharmaceutical companies to enter the market, as the incentives aimed to make the marketing of an orphan drug profitable. Yet, there was still a significant chance that costs would outweigh sales, unless the developer charged customers exorbitant prices. (Lol.)

I felt that policymakers should investigate ways of making orphan drug development profitable for a company, despite potential mediocre financial returns of the orphan drug itself.  For example, if a pharmaceutical company brought a successful orphan drug to market, the government could reward this company with a tax break of some sort. Incentives aimed at an entire business’ success would be preferable to incentives focused narrowly on the success of a particular drug. 

Years of feeling frustrated

In 2012, I attended my first SLEEP meeting in Boston and remember speaking to a researcher about the development of an orexin agonist. He mentioned that a company had looked into it, but abandoned the work. My soul felt crushed.

In 2014, I remember watching an orexin antagonist (Belsomra) gain FDA approval for insomnia - the inverse of what we needed for narcolepsy. While I understood that creating an antagonist was less complicated scientifically and that the insomnia market was much larger -- this was still hard to swallow, especially when no one seemed even interested in taking on the development of an orexin agonist for narcolepsy.

Finally -- the agonist journey began!

On Wed, Sept. 25, 2019, at the final session of the final day of the World Sleep Congress in Vancouver, Canada, Dr. Rebecca Evans took the stage to present Takeda’s first-in-human clinical trial findings for the orexin 2 receptor selective agonist, TAK-925. The room was PACKED and the the excitement palpable. I shared more about this moving experience here.

Since then, it's been a rollercoaster, but the momentum is now gaining quickly. Each SLEEP and World Sleep conference now seems to have more updates, and perhaps next year we'll see an orexin agonist gain FDA approval.

I don't want to jinx this, but I also just have to say, I cannot freaking wait. Thank you to the researchers, drug developers, clinicians, and clinical trial sites. But most importantly, thank you to the people living with type 1 narcolepsy, type 2 narcolepsy, and idiopathic hypersomnia who have participated in any clinical trials. Learn more about current opportunities on Project Sleep's Participate in Research page.

[1] Chen, Ingfei. "A Leap Forward but Hurdles Remain in Narcolepsy." New York Times on the web, 19 Feb. 2008. Health Guide. 29 Feb. 2008.

[2] Neuman, Ariel. "GHB’s Path to Legitimacy: An Administrative and Legislative History of Xyrem" Harvard Law School Food and Drug Law, April 2004 https://dash.harvard.edu/bitstream/handle/1/9795464/Neuman.html?sequence=2