Geoff’s Narration
The GIST
A Non-Opioid Drug for Fibromyalgia Soon to Hit the US Market
For the first time in 15 years, a drug has been approved for fibromyalgia in the U.S.
On August 15th, the FDA approved Tonmya for use in fibromyalgia (FM). It’s been a long wait – 15 years – since the last drug was approved for FM. I felt like pinching myself. Health Rising has been following the Tonmya (formerly TNX-102) saga for at least five years.
Tonmya seemed as dead as a duck at some points, and over that time, we’ve seen drugs come and go, but somehow, little Tonix Pharmaceuticals hung on through thick and thin and managed to produce a winner when others could not.
Fifteen years is a long dry spell for a disease afflicting approximately ten million people in the U.S. Seth Lederman, Tonix’s CEO, and the driver behind the drug, pointed out in our talk that the lack of drug approvals is not the FDA’s fault. The FDA is eager to approve new pain drugs that meet its standards, but drug companies are largely not stepping up to the plate.
That’s too bad. With the last 3 FDA-approved drugs (Lyrica-2007, Cymbalta-2008, and Savella-2009) producing “strikingly modest” effects, FM patients are surely ready to try a new approach. One large study reported that “only a minority of fibromyalgia patients continue taking medications for more than a short period of time due to either lack of efficacy, side effects, or both.” Even though long-term opioid use carries substantial risks and is not a good solution for many, Lederman noted that their research indicates that many doctors have turned to them, not the FDA-approved drugs, to treat fibromyalgia patients.
Getting a drug approved by the FDA, particularly if you’re a small drug company, is not for the faint of heart. Check out some recent examples in the FM and ME/CFS fields.
THE GIST
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Tomnya reduces pain by helping people with fibromyalgia achieve deeper sleep.
It took 15 years, but a 4th drug called Tonmya has been approved to treat fibromyalgia in the U.S. With the three other FDA-approved drugs (Lyrica, Cymbalta, and Savella) producing “strikingly modest” results and most patients choosing not to continue with them, the FM community was past due for a new treatment option.
- Tonix Pharmaceuticals is a small drug company, and its achievement was remarkable given the travails it went through and the inability of other drug companies (one very large) to bring their FM drugs to market.
- Tonix had to endure two failed major trials – one because the dose was too small and one because of the COVID pandemic, but persisted, and with the last two trials coming in with good numbers, the drug was approved on August 15th.
- Tonmya is nothing like the past FDA-approved drugs (an anticonvulsant and two antidepressants with pain-reducing qualities). An updated, sublingual form of Flexeril (cyclobenzaprine), which is primarily used as a muscle relaxant, Tonmya is being used by Tonix as a sleep drug.
- Tomnya shoots the drug straight into the body, thereby increasing its bioavailability and efficiency, and bypassing the toxicity problems that were relegating Flexeril to short-term use.
- Tonmya is different from other sleep drugs in that it blocks four receptors associated with increased alertness. Its goal is not to reduce insomnia but to enhance deep sleep in FM.
- It’s not a miracle drug. It will not take your fibromyalgia away, and not everyone with fibromyalgia benefits. Studies in over 1000 people with FM show, though, that Tonmya consistently produces “clinically meaningful”; i.e., clearly noticeable improvements in pain, fatigue, and sleep in the fibromyalgia population at large.
- Side effects are minimal with a very small percentage of participants reporting fatigue, and others reporting temporary sensations such as tingling in the mouth when the dose is taken.
- Tonix will become available in the US in the 4th quarter of this year. Costs and insurance coverage are not yet available. Tonix is only approved in the US but the company hopes to become available in other countries over time.
- Pain specialists were happy to see a new treatment approach become available. Citing the limited and poor treatment options available, Philip Mease, M.D., Director of Rheumatology Research at the Providence Swedish Medical Center, said “Tonmya is a novel treatment approach that targets nonrestorative sleep that… can impact core symptoms, specifically pain.”
Misses
Crossing the “valley of death” where most drugs go to die is not easy. Somehow, Tonix, a small drug company, made it.
Xyrem did well in its Phase 3 trial. In 2010, though, after the FDA required what Jazz Pharmaceutical considered crippling conditions for approval, the company stopped trying to get approval for Xyrem in fibromyalgia. (The active component of the drug (GHB) had been used as a date rape drug). The company CEO, Bruce Cozzad stated, “we continue to believe there is a significant unmet medical need among fibromyalgia patients that could be met by JZP-6”. Interestingly, Xyrem, like Tonmya, sought to reduce FM patients’ pain by improving their sleep.
The pharmaceutical giant Daichii-Sankyo was so confident of their upgrade of the upgrade (a better version of Lyrica called mirogabalin) that it went straight to a huge Phase III trial (3,600 patients in 300 centers worldwide) and failed. It blamed changed criteria by the FDA for the failure. (Mirogabalin is now approved for neuropathic pain conditions in Japan, South Korea, Taiwan, Thailand, and China but not the U.S.)
Skip Pridgen, M.D, has been trying to get a duo-antiviral drug approach to fibromyalgia approved for over a decade. Pridgen first formed Innovative Med Concepts to bring the drug to market, then there was Virios, which is now apparently Dogwood Therapeutics and is not moving forward with the drug. Dr. Pridgen reported that his new company, PridCor Therapeutics, had developed a combo that is targeting long COVID, which he believes can be applied to MECFS, FM and IBS with very good results. A paper is about to be published.
Many ways to fail on the pathway to FDA approval clearly exist.
Tonix’s Long and Winding Path
I talked with Seth Lederman, CEO of Tonix Pharmaceuticals, about Tonmya’s long and winding path to approval, what it does, how it’s different from past FDA-approved drugs for FM, when it will be available, and how the ME/CFS field could help.
Tonix’s path with Tonmya was no less easy. The company actually abandoned Tonix after the first big trial went belly up, but then, after a higher dose worked in a PTSD trial, it relaunched the drug in fibromyalgia. They got the dose right, but the timing was lousy, and the COVID pandemic subsequently tanked the trial.
Not many companies would keep going after two major failed trials, but Tonix retrenched, did a deep dive into their numbers, found they looked good, and persevered.
At times, it seemed like it was touch-and-go for Tonix. It was in penny stock territory for a while, but the last two trials, aptly named RESILIENT and RELIEF phase III trials, yielded promising results, and the drug was FDA-approved for FM this month.
Tonmya – a Sleep Drug for Pain in Fibromyalgia
Tonmya is nothing like the past FDA-approved drugs (an anticonvulsant, and two antidepressants with pain-reducing qualities). An updated, sublingual form of Flexeril (cyclobenzaprine), which is primarily used as a muscle relaxant, Tonmya is being used by Tonix as a sleep drug.
Tomnya reduces pain by helping people with fibromyalgia sleep better.
As Seth noted in our talk, Tomnya’s precursor, cyclobenzaprine may have been the subject of the first major fibromyalgia drug trial. The drug worked well for a month, but after that, side effects like dry mouth, somnolence, dizziness, drowsiness/fatigue, and weight gain obliterated its effects. It turned out that over time, a metabolite of the drug built up in patients’ systems, causing the side effects.
The Flexeril trials caused the European Alliance of Associations for Rheumatology to give it a weak recommendation, based, interestingly, on a trend of improvement in sleep disturbance.
That caught the eye of Seth Lederman, then a professor of rheumatology at Columbia. Lederman was well acquainted with the work of Harvey Moldofsky, a pioneering sleep and pain researcher at the University of Toronto. Citing the interruptions in sleep he found back in 1975, Moldofsky proposed that the “fibrositis” symptom complex be considered a “non-restorative sleep syndrome”.
In 1993, Moldofsky reported that “chronic fatigue syndrome and fibromyalgia have similar disordered sleep physiology, namely an alpha rhythm disturbance (7.5-11 Hz) in the electroencephalogram (EEG), within non-rapid eye movement (NREM) sleep that accompanies increased nocturnal vigilance and light, unrefreshing sleep.” It’s the “nocturnal vigilance” and light, unrefreshing sleep that sets diseases like ME/CFS and FM apart. More recent research calls this a “hyperarousal sleep disorder”.
Indeed, several studies suggest that the sympathetic nervous system (fight/flight) activation and sleep fragmentation play a key role in these diseases. It may not be so much that ME/CFS/FM patients are not getting enough deep sleep but that their deep sleep is not deep enough. A 2020 Australian ME/CFS sleep study concluded:
“Autonomic hypervigilance during the deeper, recuperative stages of sleep is associated with poor quality sleep and self-reported wellbeing.”
It was Moldofsky’s work that prompted Lederman to develop Tonmya, a sublingual form of Flexeril, to improve sleep and subsequently pain in FM. Ironically, Moldofsky, who was a founding member of Tonix’s scientific advisory board, died the day Tonmya was approved.
Tonmya shoots the drug straight into the body, thereby increasing its bioavailability and efficiency, and bypassing the toxicity problems that were relegating Flexeril to short-term use.
Tonix’s goal is not to produce longer sleep nor to prevent insomnia, but deeper, more refreshing sleep. By reducing the activity of nervous system pathways associated with alertness and vigilance during sleep – and thereby relieving pain as well, Tonix aimed Tonmya at key areas of FM (and ME/CFS). It’s different from other sleep drugs in that it blocks 4 receptors associated with increased alertness. It’s notable that the hypnotic sleep drug Ambien, which does increase sleep times but does not affect deep sleep, did not improve pain levels in FM.
Not a Miracle Drug
Tonmya is not a miracle drug. Not everyone with fibromyalgia benefits, and those who do benefit don’t suddenly lose their pain or start sleeping the sleep of the dead. What studies in over 1,000 people with FM do show, though, is that Tonmya consistently produces “clinically meaningful”; i.e., clearly noticeable improvements in pain, fatigue, and sleep in the fibromyalgia population at large.
Note that FDA approval is not a guarantee that everyone or even a majority of FM patients will respond. Like any drug, some people will respond very well to the drug, some people will do moderately well, some people will not respond, and a few will do poorly.
Major symptoms
- Pain Intensity – The mean reduction pain intensity (numerical rating scale) of about 30% that Tonmya produced in the latest trial is considered a “a clinically important” improvement. (The participants in the placebo arm received a modest improvement in pain.) Twenty-two percent of patients reported they’d received a >50% improvement in pain.
- Fibromyalgia Impact – The reduction in Fibromyalgia Impact Questionnaire score (FIQR) (-12.2) eflected a “noticeable, beneficial change in fibromyalgia symptoms and quality of life” (but is at around the threshold for “a clinically important difference”.)
- Fatigue – The 7.2 reduction in the PROMIS Fatigue Score signifies “a substantial positive change in fatigue symptoms”.
- Sleep – Likewise, the -1.7 sleep diary score signifies a “moderate and clinically meaningful improvement” which constitutes a ” clear and beneficial shift in sleep quality”.
While Tonmya didn’t eliminate fibromyalgia, it clearly produced significant improvements in major symptom areas.
Side Effects
The patient retention rate (81%) in the latest Tonmya trial is considered a “strong result,” and side effects were quite manageable. The most common systemic side-effects were not common at all and included headache (3% vs 1.8% placebo) and somnolence (drowsiness – 3% vs 1.3%). Other localized side effects caused by the sublingual (under the tongue) application (numbness (23.4% vs 0.4%), product taste abnormal (11.3% vs 0.9%), and tingling (6.9% vs 0.9%) were transitory.
Response
Pain specialists were happy to see a new treatment approach become available. Citing the limited and poor treatment options available, Philip Mease, M.D., Director of Rheumatology Research at the Providence Swedish Medical Center, said:
Tonmya is a novel treatment approach that targets nonrestorative sleep that… can impact core symptoms, specifically pain.”
Sharon Waldrop, the founder of the Fibromyalgia Association, stated, “
For over 15 years, this community has been underserved and waiting for new treatment options. This approval is a promising step forward and brings renewed hope to millions.”
Availability / Costs / Insurance
Tonix, a small drug company – but growing larger by the minute – is going to take on production, packaging, marketing, etc. itself. Lederman told Fierce Pharma:
“Our approach is to be flexible, see what works, what doesn’t work. We do believe that this could be—maybe should be—a big pharma drug. But we’ve also seen that the trend in the industry is that more and more—particularly in the [central nervous system] space—that companies have to launch the drug themselves.”
Tonmya will be available later this year. Costs have not been announced, and Lederman said, if I got it right, that talks with the insurance companies are ongoing. Tonmya is not approved outside of the U.S., but as soon as the approval was announced, Lederman said Tonix was thinking about Canada, Europe (which has no approved drugs for FM), and Asia.
Tonmya is taken once at night before bed. The doses begin low for the first two weeks and then ramp up. See prescribing information here.
Lessons for ME/CFS
“If you don’t have an endpoint you don’t have a drug” Lederman
Lederman noted the reason fibromyalgia now has 4 FDA-approved drugs but has never had a biological biomarker is that FDA-validated endpoints for pain exist. That process started in the early 2000s by a man named Lee Simon at the FDA’s pain division. Simon recognized that fibromyalgia was real and that drug companies could use assessments of daily pain to validate their drugs for fibromyalgia.
No such endpoint currently exists for fatigue in ME/CFS or any other disease. (One reason Tonix cannot claim that Tonmya helps with fatigue, even though the trials suggested that it does, is apparently that no validated endpoints for fatigue exist.) Lederman noted, though, that a recent report put out by the National Academies of Science, Engineering, and Medicine on chronic Lyme uses the work of fibromyalgia as a paradigm for moving forward with drug development in infection-associated chronic illnesses.
*Full disclosure – When Tonix Pharmaceuticals was a penny stock, I, feeling that FDA approval was imminent, for the first time in my life, bought some stock! I was right about the approval, but wrong about everything else. The stock was diluted at least once, and my small investment disappeared. It would take a miracle to break even at this point (lol).
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In the back of my mind for several years now i kept thinking that a cause will never be found and pharma will intervene with some drug(s) that will only mask symptoms and possibly do more harm..and now we see it unfolding
No drugs for this guy.Nobody knows what these or any other drug from big or little pharma does to people 10, 20, or 30 years down the road.
What happens when these drugs do harm?Good luck trying to win litigation and the lawyer that represents you laughs all the way to the bank. I was represented by a bad lawyer that took peoples monies held in trust and blew it all away at the local casino. What happened to this lawyer…he was asked if he wanted his lawyers license back and told he could keep practicing if he wanted to.
Some punishment hey
This drug scenario has been played out in history over and over and over meanwhile people ard finding real true cures on their own.
I went around in circles of md’s thinking that I just need to find the right dr. But I never did.im convinced the system is very broken and driven only by profit off of,in these cases, very vulnerable people.
Thats why we need to find the true cause of what these illnesses are…not bandaids.
Not sure why this is taking years and years for the REAL SCIENCE🤔
Pharma companies conduct good standard science, it’s not some big conspiracy to harm people. In fact much of basic research done at universities is then brought to pharma to translate into targeting through drugs. There is no clear mechanism in fibromyalgia like ME/CFS, but we know sleep is a major problem that’s intertwined with pain. Lots of REAL SCIENCE in that. And so if we can have something that helps get better sleep that’ll help. It’s not going to cure it. Some diseases are simple and caused by one defective gene so you can replace that gene or add back the protein and you’re fine. That’s not this kind of disease. We should applaud Tonix for being one of the few companies willing to spend this much money to see something through to approval.
As much science as during the coronavirus pandemic? Since then, I’ve been fed up with medications! Zero trust in pharmaceuticals, and certainly not in the FDA!
Bam!
I for one am excited to try it when it comes to Canada….After 35 yrs of fm pain ,thank you Tonix …
“will intervene with some drug(s) that will only mask symptoms and possibly do more harm..and now we see it unfolding”
But, but, Buckey….is getting more deep sleep masking symptoms or is getting more deep sleep? Is getting more uninterrupted sleep masking symptoms or is it getting more uninterrupted sleep?
Tonmya was based on “real science”: dozens of studies by Moldofsky showing that poor sleep results in more pain. (My pain hypersensitivity goes up after a poor nights sleep).
Why don’t we have more answers? Why aren’t we at the core of FM yet? Funding….The NIH is spending $1.8 dollars per year per fibromyalgia patient.
I concur. My pain is in direct proportion to the quality of sleep I had. Tonmya is no “magic bullet,” but it can improve the quality of life by reducing pain and probably brain fog. The result should be overall better functioning.
Well written and i couldn’t agree more!
Buckey, your pessimism towards the pharmaceutical industry is understandable, yes, and whatever happened with the lawyer is too. It’s difficult to keep in mind that this huge impersonal system of drug manufacture is truly designed to provide healthcare products, and does in fact do so. Inefficiently, yes, and slowly, yes too.
But it does respond. With chemical mixtures that produce side effects, yes to this as well.
Still, holistic or functional medicine is no more effective than allopathic medicine, and everything we put in our bodies, regardless of how “organic” it is, contributes to a process (combustion) that will cause our deaths in time (no more than 110 years according to the most recent data I’ve read) under the best of conditions.
If the Sackler family had not taken an ethical off-ramp with Purdue Pharma, we would all have access to drugs that help relive pain while in the meantime other drugs could be developed. As it stands, we live in relative misery while we wait. That this feels unfair goes without saying.
Still, we are a market ten million strong, and only becoming larger. Drugs are developing in response to this market. They will come. That we may not live to see the day cfc/fm are “cured” is true. Then again…we must keep the faith for those who come after us. Our children and grandchildren will benefit from our continuing raised voices for progress. SAB
Buckey. You are “singing my song”. I have13 platinum coils in my brain and am losing my vision in my left eye. All this because of a test of treatment for mast cell disorder with two small doses of antihistamines, Singulair and Tagamet. This combination triggered narrow angle glaucoma which was followed by a laser procedure and then a 7 hour brain surgery.
Reactions to all kinds of chemicals, meds, foods, etc. have always been some of my most debilitating symptoms. I had to quit my job as an advertising copywriter because I couldn’t pick up work in places like print shops where they are using toxic inks.
Cipro for a UTI nearly killed me.
And it is not just pharmaceuticals. I have a drawerful of supplements that I just can’t take.
ME/CFS and Long Covid (I have both) can cause mast cell problems. No one knows why, because no one knows what is causing the illnesses and I am not sure that anyone really cares as long as there is money to be made on treatments that may or may not make you better. And in my case, made me significantly worse.
There is money to be made on the chronically ill and desperate. Finding a cause and specific cure is a short term financial gain and likely not of interest to big pharma. They want long-term problems that lots of people have that they can treat forever.
Wow, I can relate.
I also lost color vision in my left eye after an mRNA Pfizer shot, and it triggered Stevens-Johnson Syndrome (SJS) confirmed by 2 doctors.
Now diagnosed with kidney stones.
I forgot to mention that Cipro, in combination with Vancomycin after sepsis (8 weeks), worsened my muscle weakness—possibly due to sarcolemma damage.
I for once feel some hope that a company has stayed the course and not put total profit over a treatment.
Thus said, we shall see.
I, for one, I’m anxious to try this new treatment.
It sounds promising. I’ve tried all the others…. Why not this one?
I started adding Baclofen (muscle relaxer) onto my regime a couple of years for Fibromyalgia, along with a medley of other things. It has helped so much! I was a pharma rep so the first thing I do is google a new medication. This is a sublingual form of Flexeril, another muscle relaxer. I would google all muscle relaxers and find the one with the least side effects and then the lowest dose. Ask your primary care physician (PCP) to write a prescription for the generic. Probably a free co-pay. Try it before you spend time and money on a new drug, that’s really an old drug reinvented in a sublingual form. We have enough issues without the added expense of a drug that’s not on formulary and your PCP will have to jump through hoops to get the insurance company to fill it at the pharmacy. Why pay $100 co-pay when you can get a zero-dollar co-pay. Everything old is new again.
Did you read the part about how after a month a metabolite builds up with oral Flexeril, that obliterates any benefits to sleep?
As a pharma rep you should know this isn’t the same as Flexeril it’s formulated differently to change its metabolism and thereby the way it acts (yes muscle relaxers knock you out, this is meant to actually last longer to continue improving sleep). So it’s not interchangeable with other cheaper muscle relaxants nor should people use this while taking other muscle relaxants.
It worked miracles for me. I started with a quarter of 10mg. 2.5 mg. Just trying to help the people searching for answers. I’ve had fibro for 15 years. Finally sleeping like a dream.
That’s how Daniel Clauw uses it – splits it into quarters if I remember correctly, to bypass the metabolic problems. Seems to work!
Glad you had a good result with Baclofen. Because my husband came across something that suggested Baclofen would help with pain, I asked my doctor to prescribe it.
Unfortunately, for me it was a disaster – after a few very good days. Took a couple of weeks to get rid of the brain fog and gastric complications.
My previous sleep neurologist was willing to try Xyrem for my FM, and it definitely helped. Unfortunately, after about one month taking it each night, I started becoming very anxious and paranoid, almost borderline psychotic. He told me to stop, citing that about one in five patients he prescribed Xyrem to, mostly for narcolepsy, developed this complication. And I was only taking one-third the standard dose (couldn’t wake up for ten hours on the first of two nightly doses). Totally sucked, since I had far less pain and more energy with Xyrem than without. But trading one’s sanity for symptom relief ain’t worth it.
Right- sanity comes first – but note how much a sleep drug helped for a while….Maybe Moldofsky was right – FM is, in part, a sleep disorder, and if you can get better deep and uninterrupted sleep everything else will improve.
Cort, I am super confident that FM is mainly a sleeping disorder. My personal theory is that FM is the bastard stepchild of narcolepsy.
Too many of us have been diagnosed with several different sleep disorders in addition to having traditional narcolepsy symptoms without actually having narcolepsy, or so the doctors claim. I’ve been at Stanford sleep neurology for almost 20 years, and the doctors I’ve seen still claim I don’t have narcolepsy. I have the narc genes, one of my mom’s sisters had sleep drop attacks when pregnant, I’ve had cataplectic drop attacks when startled or severely frightened, and I fell asleep in less than two minutes during the multiple sleep latency test. But because I didn’t fall into REM sleep in the first five minutes, they claimed no narcolepsy, even though I’ve never produced more than a few minutes of REM sleep in the sleep lab, like many other FM patients. That’s why I call it the bastard stepchild of narcolepsy.
Maybe someday sleep researchers will get this, hopefully.
I have an interview with an FM/ME/CFS doc who has these diseases and believes that ME/CFS/FM is a kind of narcolepsy as well. He’s used Xyrem for decades and used to prescribe it widely. Unfortunately, I fell out of touch with him but I think I will post it.
Cool.
Thanks, Cort!
When I was with Kaiser (insurance) and having body wide muscle pain, I was prescribed Flexeril. I had to take a half dose b because I was too groggy the next day with the dose they gave me (10 mg.) Later Kaiser took it away and told me that it was not appropriate for older adults. Nobody explained why but later I found it on a list of drugs which affected brain function. Also it can make some individuals dizzy and give them a fall risk. Both reasons apply especially to seniors. If I remember correctly, it also had a very long half life.
It did help with sleep and also pain, but alas, it became no longer available. I wonder if either of these side effects would apply to this new drug.
It appears that they do not – at least not in above 2% I think it was, of patients. Only fatigue and drowsiness – about 3% – were in that category.
10 mgs. is too much for a fibromyalgia patient. Check this out from Daniel Clauw
You could try splitting Flexeril into quarters and see what you can tolerate and see how it goes. It’s Daniel Clauw’s favorite drug for FM – he reduces the dose so that the metabolite doesn’t build up.
From the blog
https://www.healthrising.org/blog/2024/08/31/fibromyalgia-chronic-fatigue-long-covid-central-nervous-system/
“At 10 mg, Flexeril was so sedating to FM patients that he believes sensitivity to it could be considered almost a biomarker for the disease. Even a milligram, more or less, can make a difference. When he cut down the dose to 5 or even 2.5 mg, though, they could tolerate it, use it long term, and benefit from it.”
No worries Cort. I guess I wasn’t clear about my dose. I was cutting the normal 10 mg in half to 5 mg. Even then there was a mild bit of a morning after effect. I was using it for the muscle spasms (and pain) of Ehlers-Danlos–not for fibromyalgia. It worked well. I didn’t however, use it every evening–just when I needed extra support.
My modus oporandi is ‘listen to your body’ no matter what the doctors might say. I am exceedingly sensitive to most medications and so need to do this while doctors usually prescribe a dose which works for ‘most’ people.
I am so thrilled about this but was disheartened to see the reaction from those in the fibro community online, mostly of skepticism and the misunderstanding that this is the “same as Flexeril”. This is a great breakthrough and has the best clinical trial data yet for fibro. About half of patients had at least 30% or greater improvement in pain which is more than the roughly 1/3 who benefited from Lyrica or Savella. Hope people try this and also that it’s affordable and covered by insurance. Now on to the task of trying to educate my rheumatologist about it so she’ll consider prescribing it when available.
Good luck! One nice thing about Tonmya was the low level of side effects. I don’t know if you can say that about Savella. I asked AI what the common side effects of Savella are – and here they are: The most common side effects of Savella (milnacipran), a medication used to treat fibromyalgia, include:
Nausea (most common)
Headache
Constipation
Dizziness
Insomnia (trouble sleeping)
Hot flushes/flushing (feeling of warmth or redness)
Increased sweating
Vomiting
Palpitations (irregular or pounding heartbeat)
Increased heart rate
Dry mouth
Increased blood pressure
Quite the list!
Thanks Cort and agree! My rheum is all about trying to get me off so many meds, which I don’t disagree wth. I’m hoping that if this can improve my sleep and therefore pain, maybe I CAN lower or eliminate Lyrica and some others. And yes the Tonmya side effect profile is very good per the US PI, compared with any other FDA approved fibro meds and off-label ones.
In our talk, Lederman said that one of Tonix’s hopes is that it will be able to show that using Tonmya allows FM patients to get off other drugs. Let’s hope!
I tried going without a prescription medication. I took melatonin for awhile, but it stopped working after a year. I noticed a sharp increase in neuroinflammation as well. I am now taking Trazadone which is helping with sleep and reducing the inflammation.
My concern with Tonix is that it is a small company that intends to do its own distribution and marketing. I saw Novavax, a small company that produced a traditional Covid drug, struggle to do its own distribution which cause huge delays in getting the drug to the public. I hope they are not underestimating what it will take to bring the drug to market.
Let’s hope they’re ready to do that. They seem to have been planning to do this for quite some time and purchased the rights to some other drugs to get them ready.
I saw your headline & was hopeful this new drug would help with my extremely low amount of deep sleep. I often register zero or 1-2 minutes. Then I saw its reformation of Flexeril, which I’m allergic to, so I guess it’s not in the cards for me. Hopefully, it’ll help others tho.
Have you tried Flexeril in low doses?
You could try splitting Flexeril into quarters and see what you can tolerate and see how it goes. It’s Daniel Clauw’s favorite drug for FM – he reduces the dose so that the metabolite doesn’t build up.
From the Daniel Clauw blog
https://www.healthrising.org/blog/2024/08/31/fibromyalgia-chronic-fatigue-long-covid-central-nervous-system/
“At 10 mg, Flexeril was so sedating to FM patients that he believes sensitivity to it could be considered almost a biomarker for the disease. Even a milligram, more or less, can make a difference. When he cut down the dose to 5 or even 2.5 mg, though, they could tolerate it, use it long term, and benefit from it.”
Thanks for the suggestion, but I get severe facial swelling & wheeziness, so don’t think it’d be safe to take it at all. Wouldn’t want to risk anaphylaxis. My wife who’s had idiopathic anaphylaxis her whole life wouldn’t be okay with it either. Besides, my list of allergies gets longer as I age with ME/CFS. They never seem to go the other way. Interestingly, I don’t recall Flexeril being sedating for me.
So will the UK NHS deem Tonmya safe, affordable, and allow doctors to prescribe all who would benefit. I am worried that we in the UK will have little chance of having a drug that offers more help than the current offerings. In the meantime, I will carry on with Duloxetine, having tried all the current alternatives.
You could try splitting Flexeril into quarters and see what you can tolerate and see how it goes. It’s Daniel Clauw’s favorite drug for FM – he reduces the dose so that the metabolite doesn’t build up.
From the blog
https://www.healthrising.org/blog/2024/08/31/fibromyalgia-chronic-fatigue-long-covid-central-nervous-system/
“At 10 mg, Flexeril was so sedating to FM patients that he believes sensitivity to it could be considered almost a biomarker for the disease. Even a milligram, more or less, can make a difference. When he cut down the dose to 5 or even 2.5 mg, though, they could tolerate it, use it long term, and benefit from it.”
I was on Xyrem for about 3 years. I slept deeply and woke up refreshed, without my usual stiffness. I thought Xyrem was the most wonderful drug ever invented.
I didn’t mind waking after 4 hours to take the second dose. Apparently, split doses were one of the reasons that patients in the FDA trials were reluctant to continue on this drug. I rarely experienced any side effects.
After 3 years, my doctor stopped prescribing Xyrem.
Xyrem didn’t cure me. I have and had too many chronic illnesses. But it gave me some semblance of a normal life.
I am curious about this new sublingual form of Flexeril. I had poor results with oral Amitryptilene and oral Flexeril many years ago.
Emily, all pharma companies do not do good basic science.
Case in point, Bendectin, a medication that was concocted in 1956 to treat morning sickness had no basic science supporting it. It was a marketing decision where it was determined that about half of all women had morning sickness during pregnancy and that a safe and probably effective drug could have huge profit potential.
An antihistamine, an antispasmodic and vitamin B-12 were combined into Bendectin, a pill with 20 shellac coatings that you could take at night so it would be available to combat “morning” sickness.
No studies were done in pregnant women or in pregnant animals. But, Bendectin was grandfathered in…in just 28 days.
Bendectin didn’t work very well but it would have probably been benign until the Kefaufer-Harris amendments were passed in response to the travesty of thalidomide which caused 10,000 babies to be born without limbs and other devastating birth defects. (In pre-marketing studies thalidomide was considered so safe they could kill a test animal with it.)
Since the manufacturer was having trouble proving the efficacy of Bendectin, they micro-processed the antispasmodic (which made it much, much more potent) and they removed half the shellac coatings to be sure the drug was actually being dissolved and not just passing through.
At this point, cases of children with missing limbs (whose mothers took Bendectin) started being reported to regulatory agencies from all over the world.
My son was one of these children and we only learned about Bendectin’s history from whistleblowers at the FDA who helped us with documents and information.
We were involved in a 10 year court battle and eventually got Bendectin off the world-wide market.
That said, my life has been saved by antibiotics when I had a MRSA infection and my vision (I hope) will be preserved by glaucoma drops. And my ME/CFS has been controlled by a drug (Nexavir) made by a small manufacturer.
But, the really big pharma companies are looking for diseases they can treat forever with expensive drugs.
This is a judicial opinion in a Bendectin case and if you can get through it, it will give you a new understanding of the pharm industry. https://birthdefects.org/wp-content/uploads/2014/04/Bendectin-JOP.pdf
Bendectin cases won jury awards in the millions (up to $95 million in a Washington DC case) but every single case was overturned by higher and higher courts.
I think it was also the case with the covid vaccines.
Significant Increase in Excess Deaths after Repeated COVID-19 Vaccination in Japan
https://pubmed.ncbi.nlm.nih.gov/40416011/
The more doses you get, the sooner you are likely to die. “…the more doses you get, the sooner you are likely to die, within a shorter period… A peak in mortality occurred among the vaccinated, especially between 90 and 120 days after vaccination. “A significant peak forms after three or four months,” “This is likely due to the influence of the vaccine, leading to side effects that result in death.
https://imahealth.org/experts/yasufumi-murakami/
Here we go again! I asked AI Perplexity how many studies involving how many people have shown that the COVID-19 studies have reduced mortality.
Here’s its answer.
“A comprehensive meta-analysis published in 2023 reviewed seven studies that included a combined total of 21,618,297 COVID-19 patients. This analysis found that vaccination significantly reduced mortality: unvaccinated individuals were 2.46 times more likely to die from COVID-19 than those who were vaccinated.
Another 2022 meta-analysis included 54 studies (sample sizes varied) and found that having received at least one dose of a COVID-19 vaccine reduced the risk of death by 68%, and two doses reduced it by 92%.
In summary, at least 54 studies—some including study populations in the tens of millions—have demonstrated that COVID-19 vaccines reduce mortality.”
When I asked AI Perplexity if the effects of the COVID-19 vaccines on overall mortality had been assessed it reported:
“Yes, several studies have assessed the effect of COVID-19 vaccines on overall (all-cause) mortality. Large population-based studies and meta-analyses have consistently found that COVID-19 vaccination greatly reduced the risk of death from COVID-19 without increasing the risk of death from other causes. For example, a 2023 study using national registry data found that the risk of non-COVID-19 mortality was lower or similar after vaccination compared to pre-vaccination periods across all age groups. These findings are supported by similar results in prior research, which observed no evidence that COVID-19 vaccines increase all-cause or non-COVID-19 mortality risk.”
The most important question is: for which age groups was COVID dangerous, which people were saved, how old were they? Ask AI? We know that for younger people, even under 60, this virus was hardly dangerous. Just wonder which people were saved by the mRNA vaccine.
Meta-analyses contain studies that are as comparable as possible, which also creates uncertainties. Most studies are based on models. These often contain assumptions. This also creates uncertainties. I believe there are still meta-analyses about CBT and GET as treatments for ME/CFS/FM, etc., that show exaggeratedly positive outcomes. Patients know this is wrong.
Those mRNA vaccines should never have been given to people under 60. Studies by drug manufacturers, in this case mRNA vaccines, should always be examined by independent scientists, but this often doesn’t happen. So who are these scientists? Who funded these studies? Why don’t critical scientists receive funding? Well, the answer is obvious. RFK no longer wants to fund mRNA vaccines because of, among other things, the potential for dangerous side effects and harm.
There actually aren’t meta-analyses of CBT that show dramatic improvements. The most they can say is that modest improvements in fatigue may result. I actually suspect that the metanalyses probably more than anything else are what killed the CBT field in ME/CFS. They showed it just wasn’t delivering.
I asked AI Perplexity – what effects, negative or positive did the COVID-19 vaccines have on young people. Here’s it’s answer:
Positive Effects
Vaccination greatly reduced the risk of severe illness, hospitalization, and death in children and adolescents who contracted COVID-19. For example, vaccination in teens was found to be 94% effective in preventing hospitalization and 91% effective in preventing multisystem inflammatory syndrome in children (MIS-C), a rare but serious condition linked to COVID-19 infection.
: Vaccinated children and adolescents had a much lower risk of complications like myocarditis and MIS-C after a COVID-19 infection compared to unvaccinated peers.
Vaccination had a positive relationship with mental health status in youth, with more vaccine doses correlating to reduced rates of depression, anxiety, insomnia, and post-traumatic stress disorder (PTSD). This improvement comes partly from reduced worry about infection and a return to more normal social interactions and school routines
Less Disruption to Daily Life: Vaccinated young people were less likely to miss school or activities due to illness or quarantine, supporting academic progress and social development
Negative Effects
There is an increased (though rare) risk of heart inflammation—myocarditis (heart muscle) and pericarditis (heart lining)—especially in male adolescents and after the second vaccine dose. The vast majority of these cases were mild and resolved without long-term problems, but they did require monitoring and sometimes hospitalization.
Young people, like adults, experienced mild side effects such as headache, dizziness, syncope (fainting), nausea, fever, and fatigue. Adolescents were also more likely than adults to experience syncope, loss of consciousness, chest pain, or palpitations, typically within a day or two after vaccination.
While extremely rare, some adolescents experienced severe side effects such as multisystem inflammatory syndrome (MIS-C), seizures, or demyelinating diseases following vaccination. These events were significantly less frequent than similar complications after actual COVID-19 infection in unvaccinated adolescents.
Conclusion
In summary, COVID-19 vaccines provided strong protection against severe infection and had mental health and social benefits for young people. Most side effects were mild and short-lived, while serious adverse effects were rare but monitored. The net effect has been considered positive for this age group, especially in preventing serious outcomes from the di
Thanks Cort for asking your question to AI. Here’s a meta-analysis showing a moderate to good effect on CFS through treatment with CBT. Many studies, such as the Pace trial and Prins et al., report significant effects of CBT. We know that was nonsense.
Many positive effects in medical studies are exaggerated. In practice, these are always lower. The mRNA vaccine is another example of this.
A 94% prevention of hospitalizations among young people seems highly exaggerated to me. This is also based on assumptions and models. How old were these young people? Were they hospitalized through COVID or with COVID? Did they have underlying conditions? So many factors play a role. This figure is relative. For example, how many people do you need to vaccinate to prevent one hospitalization?
Unvaccinated young people (and older ones) were no longer allowed to travel freely, go to school, the gym, or clubs. It’s logical that this group developed more mental health problems. The same thing happens when you lock people up. Those vaccines didn’t prevent that; there was simply discrimination and violations of human rights.
The median IFR was 0.0003% for ages 0-19, 0.002% for ages 20-29, 0.011% for ages 30-39, 0.035% for ages 40-49, 0.123% for ages 50-59, and 0.506% for ages 60-69.
https://pubmed.ncbi.nlm.nih.gov/36341800/
Look at how low the IFR is for young people. Mass vaccination with a new, insufficiently researched mRNA vaccine was unnecessary and irresponsible.
Gijs,
I was doing a little research on MNRA technology. This is what I found:
“Almost everybody working on Covid vaccines comes from the HIV world,” said Mitchell Warren, executive director of AVAC, a global advocacy group for HIV prevention. “Moderna had been working on mRNA-based HIV vaccine before SARS-CoV-2 was even known to exist.”
“Government funding is a crucial component of all vaccine research and development. Within a few months, Operation Warp Speed allocated $10 billion to Covid vaccine research and development. By contrast, between 2000 and 2020, the U.S. government contributed $12 billion toward HIV vaccine research and development. This funding frequently goes to private companies.”
Cort, it seems to me that Medicare Part D programs hold off on adding new, expensive drugs without any generic substitute to their formulary for as long as possible.
And I’d guess that MANY of us are on SSDI and Medicare. Those of us that are the sickest and need this drug are more likely to be on Medicare (with some luck).
It’s possible that there might be grants for this drug for fibro patients at companies like PAN but doubtful as fibro is such as relatively common condition if 10,000,000 people are affected.
And it is possible that some Medicare Part D programs will allow it with authorization from your doctor (but probably not likely as it is brand new).
What are your thoughts on this, Cort? TY for all you do for us.
I didn’t know that…Darn! (I’m on Medicare now….).
If you can’t get Tomnya you could try splitting Flexeril into quarters and see what you can tolerate and see how it goes. It’s Daniel Clauw’s favorite drug for FM – he reduces the dose so that the metabolite doesn’t build up.
From the blog
https://www.healthrising.org/blog/2024/08/31/fibromyalgia-chronic-fatigue-long-covid-central-nervous-system/
“At 10 mg, Flexeril was so sedating to FM patients that he believes sensitivity to it could be considered almost a biomarker for the disease. Even a milligram, more or less, can make a difference. When he cut down the dose to 5 or even 2.5 mg, though, they could tolerate it, use it long term, and benefit from it.”
THanks for the info and taking time to reply. Seems like I tried flexeril many years ago and for some reason didn’t stay on it, but I doubt it was such a low dose.
I’ll see what happens and consider it. Useful info that I appreciate, Cort.
The way out…
https://youtu.be/vU91aBLyMMQ?si=Y38gkZ3mceZjpL1u
Cort, thanks for the interview with Seth Lederman.
I’m still trying to make sense of Fibromyalgia.
I’ve read nearly all the reputable research papers, but my experience remains confusing:
August 2021 (Oncology): Diagnosed with Fibromyalgia (ICD: M79.70G)
May 2023 (Hematology): Lupus confirmed through lab testing—often mistaken for Fibromyalgia
So… what is it now?
None of the research addressed one important factor: how many hours a patient had gone without food before sleep.
For example, in my case—and likely for many others who are highly sensitive or immunocompromised—going more than four hours without eating before bedtime leads to waking up during the night and being unable to fall back asleep.
Agree. I have to have a hearty snack right before bed if I don’t want to wake up hungry in the night and then not be able to fall back asleep. Then, the doctors say no food 2 hours before bed to reduce acid reflux. I can’t win.
Becky:
Since I have lupus—which is often mistaken for fibromyalgia—I hadn’t been following my doctor’s advice for 8 months. My last meal, about 2 to 3 hours before bedtime, is very low in carbohydrates and high in protein, as polysaccharides (carbs) can trigger inflammation. I also take half a tablet of cetirizine before bed, which helps me sleep well for 7-8 hours and wake up feeling refreshed and energized.
WHAT is the difference between Flexiril and new drug??? I have taken flexoril since 2004
Tonmya is a sublingual formulation shoots the drug straight into the body, thereby increasing its bioavailability and efficiency, and bypassing the toxicity problems which caused drowsiness, etc. that were relegating Flexeril to short-term use.
So, is it an injection??
Very interesting. I have narcolepsy and fibromyalgia. I am well aware of the connection sleep (or lack thereof) has with pain.
Just read it at Solve M.E.
“Extracellular Vesicle Proteins in Men with ME/CFS: Changes Before and After Exercise Correlate with Key Symptoms”
Excerpt: Severity of post-exertional malaise (PEM) correlated with differences in extracellular vesicle proteins related to the endoplasmic reticulum stress response and to protein folding. In other words, the men in whom levels of these extracellular vesicle proteins changed the most also had the most severe post-exertional malaise.
https://solvecfs.org/extracellular-vesicle-proteins/
If you can, watch Jarred Younger, PhD:
Why ME/CFS “fatigue” is not normal fatigue
https://www.youtube.com/watch?v=Nx6qX-9tim4
That sounds hopeful, especially with 81% of people completing the trial. Thank you for another interesting article, Cort, and good luck with your stocks!
It’s just Flexeril SL. It doesn’t work.
Cort, thank you so much for this article and the interview, which was great. I learned so much!
I’m trying to help a family member who has Hypermobile EDS, POTS, and MCAS as well as several sleep issues (Periodic Limb Movement and Obstructive Sleep Apnea). I really have some hope now that Tonmya might help her main issues, which are fatigue, hypersomnia, and brain fog.
My worry about this drug causing a deeper sleep is that they are now saying that taking sleep medication taken over long term is increasing dementia in people as keeping the brain a sleep for longer periods of time was reacting to the drugs. So since this drug is putting you in a deeper sleep which would effect the brain more then regular sleep medication then we are facing the chance of having dementia at a earlier age.