It wasn’t supposed to go this way. Daiichi Sankyo bet big, big money that it’s safer, more effective version of Lyrica (pregabalin) called mirogabalin was going to be the next big thing in fibromaylgia (FM). It was so confident that it embarked on a global series of trials involving over 3,600 patients in 300 centers throughout North America, South America, Eastern Europe, Western Europe and the Asia Pacific region. Mirogabalin was going to do battle with Lyrica worldwide, and Daiichi Sankyo executives clearly anticipated winning.
Mirogabalin was going to take on Lyrica world-wide
They had good reason to be confident. Lyrica, mirogabalin’s predecessor, binds to a calcium channel subunit that has pain reducing and central nervous system effects. Those central nervous system effects are believed to cause its rather notorious side effects.
Mirogabalin, on the other hand, binds to a calcium channel subunit believed to have strictly analgesic; i.e. pain reducing effects. In one fell swoop, Daiichi was going to produce a drug that was not only more effective but had fewer side-effects and was longer-acting than Lyrica.
One imagined that Pfizer, Lyrica’s manufacturer, was not happy with the threat to its $600 million a year cash cow. It turned out that mirogabalin did meet its primary goal in shingles (post-herpetic neuralgia), a nasty, nasty disease – but Daiichi’s big money was on fibromyalgia. Unfortunately Daiichi’s much larger FM trials failed to produce a statistically significant reduction in FM patients’ worst daily pain score (compiled weekly) over 13 weeks. For all its problems, Lyrica has passed that test many times.
In the three 13-week, double-blind, global, phase 3 ALDAY clinical trials evaluating Mirogabalin for the treatment of pain associated with fibromyalgia, Mirogabalin did not meet the primary efficacy endpoint to demonstrate a statistically significant reduction in the weekly average of worst daily pain score from baseline to Week 13. Daiichi Sankyo
The Next Lyrica?
One wonders if the mine of calcium channel effecting drugs in fibromyalgia has finally been played out. First came Neurontin (gabapentin), then there was Lyrica (pregabalin) and now there’s mirogabalin. Gapabentin enacarbil (Horizant) is a prodrug to Gabapentin which has been FDA approved for moderate to severe restless leg syndrome and shingles. Several other efforts at producing drugs in this class have failed.
Pfizer’s patent on Lyrica will expire in 2018, allowing generics to enter the market. The pressure’s on for Pfizer to find a replacement before then. Pfizer’s apparently found an analogue for Lyrica called 4-methylpregabalin that, according to Wikipedia, has proved several times more potent in animals than Lyrica. It’s apparently able to easily pass through the blood-brain barrier. No trials appear to be underway, though.
Tough Disease
The rapid approval of three drugs (Lyrica, Cymbalta, Savella) over a couple of years in the late 2000’s must have made FM seem like an easy sell. With two big recent failures (TNX-102, mirogabalin) drug companies are probably thinking differently.
Of the five drugs up for approval only one is left – but a new one is being tested.
The collapse of Tonix’s flexeril derivative (TNX-102) was perhaps even more surprising. Daiichi didn’t do a bunch of phase II mirogabalin trials, but Tonix evaluated TNX-102 in at least four FM trials and seven other studies. The trial indicated that Tonix did have its benefits, but it failed to reduce pain significantly in at least 30% of the FM patients taking it, and Tonix is no longer interested in it for FM.
Last year both the Synergy trial (methylphenidate/supplements) in ME/CFS and the highly touted antiherpesvirus drug CMX-001 or Brindcifovir in transplant patients also failed to reach their endpoints.
The Future
So where are we now with FM drugs? Just a few years ago five drugs were considered possible candidates for FDA approval. Two are gone and no studies are underway in two of the others (time-release formulation of Lyrica, TD-9855 – NSRI. TD-9855 is being assessed for neurogenic orthostatic hypotension.) The last man standing from that group is Dr. Pridgen’s antiviral drug combination trial (IMC-1) which is slated to begin Phase III trials at the end of this year or next year. Other possibilities are popping up, however.
A new drug, ASP8062, which enhances GABA functioning, recently popped up on Clinicaltrials.gov. It’s Phase II trial to establish safety and provide data on efficacy began in May of this year, and is being tested in 22 locations around the U.S.. (For more information ontact: Astellas Pharma Global Development800-888-7704 ext 5473 or astellas.registration@astellas.com
Survovexant, an intriguing sleep drug, that targets a small area of the brain (in contrast to most sleep drugs) and may have beneficial autonomic nervous system effects, is now recruiting FM patients for a trial in Michigan.
Propanolol, a blood pressure drug sometimes uses to treat postural orthostatic tachycardia syndrome (POTS), is not usually thought of as a pain-reliever, but several studies suggest it could be helpful for fibromyalgia. One FM study found that low dose propanolol reduced pain, improved orthostatic intolerance and even increased cortisol levels. Dr. Light believes propanolol may block sensory receptors that are sending too many pain signals to the brain in FM. (The trial is active but not recruiting).
The three small low-dose naltrexone (LDN) studies in FM have made a big difference but what we really need is a larger trial. A major LDN trial (n=140) will wrap up in Norway in December. Several transcranial magnetic stimulation trials are underway as well.
Next up – Jarred Younger tackles LDN and fibromyalgia again.
I use low dose naltrexone for my fibro pain and it works great. I started at the lowest dose available, 0.2 mg, since I have bad reactions to pharmaceuticals in general. I am now stabilized at 0.8 mg, which I take before going to bed. My symptoms tend to be greater in the winter (I live in the north) than the summer, but overall everything is much better than it was before the LDN. Now if I could just get something for my crushing fatigue…
That just goes to show, Kristi, that we need better dosing information on FM. The dose in that Norway trial is 4.5 mgs and here you are benefiting at .8mg! Thanks for passing that on.
I treat both FM and ME/CFS and there’s a lot of overlap between fibro and ME/CFS fatigue symptoms. Often people qualify for both diagnoses. Unfortunately, there aren’t generally great treatments for underlying cause available yet, but often fibro fatigue responds to similar measures that one would use for ME/CFS (for example, evaluating and treating orthostatic intolerance – symptoms that get worse with standing).
Any medicine even carrying sucrose lactose fructose will not work 100% besides Fibro CFS is EDS, hopefully, these Nutters will realize this
Lactose Intolerance or sensitivity, and dairy in general, does make ME/CFS and FM worse, as does certain artifical ‘lake’ colorings (=”known neurotoxins in children”) & other common ‘inert’ non-natural ingredients and fillers in drugs.
I just wonder if that is why some of these Trials are not getting the results they expected?
And why CFS & FM people find that despite taking several Rx medications, they are not getting better?
I find it appalling the way severe fibromyalgia pts are treated thankfully I ran into a Stanford Dr studied it. Controlled severe fibromyalgia for 8 years completely undetectable w MS Cotin & Hydrocodone I actually decreased over 3 years until group of nurses in Ohio literally cut me down to the floor in inhumane pain again. Also placed something thin sharp near epidural area of spine “ unauthorized “ denying when I felt it now I “ pop out “ from the area & All over w obvious side effects from burns hives electrical zaps non fibromyalgia related & fibromyalgia not controlled 4 years later on exact same working regimen suddenly is blocked “ opiods “ though never abused or increased & was mentally retardation from LYRICA cymbalta “ manglia” w an array of side effects n allergies to 200 previous meds yet the fasad continues and doctors act like they are clueless stil 2017-2022 visible gage of body sight sound etc. burn marks streaks down limbs w mass heat like a methadone w electrical current threw me..all because most don’t comprehend the nerological Miss fire and that opiods stop it & true fibromyalgia ppl don’t get a high and they never stop working. I’d love to know who authorized this medical trial and why what would fix fibromyalgia all together is kept hidden? Please advise to date now I barely stand walk sit on a regimen proven to give me quality back physically
The answer to these surprises, is probably to be found when we understand the pathways that cause the actual dysfunctions in muscle tissues, that quite logically result in pain in most people with FM. When we understand that, we will understand why different pain suppressing drugs that work through this or that channel, failed to work with FM.
I wish the research was being focused on finding the pathways that cause the actual muscle-tissue dysfunctions in the first place. It may be in the renal system or maybe in the metabolism. As long as researchers are focused on the Central Nervous System, they are like cancer researchers trying to alleviate the failure in patients organs without noticing “tumours” yet.
It is interesting just how confident Daichii was in this drug. They enrolled over 3,500 patients in several continents. They clearly thought they were impacting a key mechanism that produces pain in FM. To be so wrong is kind of stunning and does, at least to this laymen’s thinking, suggests that the cause of FM pain does indeed lie far from this area. Perhaps the search for more calcium channel affecting drugs is over (???).
Studies do indicate, though, that Lyrica does downregulate the microglia that Younger believes are involved in FM. (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4178248/)
I’m surprised that no one on Health Rising, at least I can find, has mentioned Epicgenetics FM/a test and the vaccine being sent by them to the FDA for approval, probably Phase 2. Medicare and some insurers will pay for the test, around $1000, but I first paid cash to avoid problems if I was in the 7% false negative group and am filing for reimbursement. In the near future, the M.D. CEO of Epicgenetics, followed by the Immunology M.D. who will administer the vaccine, followed by yours truly as a typical FM patient hoping this works, will be interviewed separately on ABC news in a health segment on the test and fibromyalgia. Dr. Gillis is convinced he has found a cure and I hope to be the first one in line to get the injection, may take several years to get approval. I will post here when I find when the show will air, am a bit nervous as they came to my home and asked lots of questions.
Bravo. I feel the same way. Let’s understand the disorder and then find some way to manage the disease.
Vaccines may work on future generations, but will not be effective for someone with the disorder. That is why, for the most part, we give vaccines early in childhood.
I agree that unless researchers try and find out what is causing pain in the fascia (membrane which encapsulates skeletal muscles) of our muscles, it will be difficlt to treat Fibromyalgia at the cause. I do believe, however, that since so little is known about the actual cause, that symptom relief is the next best thing. I have be able to get symptom relief from two very unorthodox drugs, but I still don’t have a functioning body. If I do nothing much I’m in very little pain. However the minute I try easing into any exercise, the pain just comes right back. My challenge is to find out if the pain I have is FM related or is caused by the deterioration that’s been diagnosed in certain tendons, but not in others. It’s complex, as are most issue involving FM and ME, it’s exhausting trying to find the right doctors to help. I find that lack of a curious mind in my doctors is the biggest hurdle to moving forward.
“I find that lack of a curious mind in my doctors is the biggest hurdle to moving forward.” I absolutely agree. I was trying all kinds of things, and some of it may have even been helping a little but I couldn’t handle how much suffering I was going through simply because doctors didn’t seem very interested in figuring out a way to help me.
They focus on the CNS because that’s what FM is, a CNS condition which causes muscle pain.
Although the CNS is involved, I believe Dr. Pridgen is correct that the HSV-1 virus is the culprit. The cold sore virus has gone after the CNS as it loves nerve tissue. Cold sores are almost never seen in Fibro patients because that is not the pathway it took in our bodies.
IMC-1 is the drug’s name which is being tested and the FDA has fast tracked the Phase III clinical trial. It will suppress the virus. http://me-pedia.org/wiki/Fibromyalgia#IMC-1
I take 75gm of lurica for my neuropathy pain in my feet gosh couldn’t live without it, the pain is hell, don’t think it helps at all with my fibro, as when I get slack or think I am ok and forget to take my other medication I stiffen up fatigue comes back and pain all over
For my fibro they only thing that works for me is pyralin en 500mg-200
I take 3 tablets twice a day has completely changed my life
Congratulations Catherine and thanks for passing that on. I hadn’t heard of it being used in FM. I wonder how your doctor decided on it.
Pyralin EN is used to treat and manage ulcerative colitis and Crohn’s disease which are inflammatory bowel diseases.
Pyralin EN is also used to treat rheumatoid arthritis which is a painful joint disease.
Pyralin EN helps prevent damage to your joints. It works to slowly reduce the swelling and stiffness in your joints. It is usually given when a group of medicines known as non-steroidal anti-inflammatory drugs (NSAIDs) are not working.
How Pyralin EN works
The active substance in Pyralin EN is sulfasalazine. It has a number of effects in the body. It is an immunosuppressive and an anti- inflammatory medicine. http://www.news-medical.net/drugs/Pyralin-EN.aspx
Thanks for this explanation of Pyralin EN. Since I’m on blood thinners, I’m always looking for a drug that isn’t an NSAID for some relief for inflammation. I’ve been able to get some relief from another drug, but it’s expensive and self pay. I also suffer from 3 major autoimmune diseases so an immunosuppressive may help as well. All I’ve been told is that my immune system isn’t funtioning, so I’m not sure if it would help or hurt that situation. I’ll have to ask my doctor.
Yes, thanks, Catherine, that is very interesting. My son has had severe Crohn’s for 20 years and, after 30 years with bad fibro, I have been wondering if it is a variant of CD. Joint problems or stiffness are not my problems, rather body and specific nasty pains, but I will start researching the pyralin, maybe my PCP will consider it. My feet are always hell, unaffected by Tramadol or anything else.
I had the Epigenetics FM/A test – positive (92, whatever that means), and shortly thereafter began low dose naltrexone at various doses over about a four month period. Unfortunately it did not work for me at all at any dose. Would love to have more possible treatments, and ones with plausible rationales for how and why they work.
LDN does not appear to work for about 40% of FM patients…Have you tried medical marijuana or other cannabis preparations? Survey’s suggest that cannabis (low THC-high CBD (???)) preparations may be the most effective treatment.
I’ve been taking LDN for years, it helps, but not enough. Recently I started taking CBD (drops under the tongue)in addition to LDN and melatonin, which really helps me sleep better (helps with pain, so I don’t wake up to turn over every 15 minutes or so). Better sleep gives me less pain during the day, it broke the fibro cycle.
Getting decent sleep is so important and CBD oil and other cannabis products are proving to be really helpful. Cannabis and LDN are two substances FM really could really, really use more research on. Congrats on breaking the cycle 🙂
So glad you are getting some relief! I don’t do well at all when I don’t sleep. I recently suffered the death of my sweet Dad. it’s set me back in just about every area. You’d think living in SF there would be all sorts of places I could get CBD, but you need a license and then the pot is super expensive. I’ve heard of sympathetic growers, but can’t find one in SF. Go figure!
N-Acetyl-Cysteine (NAC), is an antioxidant, a relative of glutathione + may be an option for those stugging with pain. Mine is primarily in hips + neck/skull base/paraspinals. I’ve been taking NAC 600mg 2-3×/day for the past 3 weeks and have noticed a marked reduction in pain to the point that I’ve been able to cut back on neurontin . The recommended dose on the label states “1 capsule, 600mg, once/day.” Purchased it at Vitamin Shoppe. Hope this gives someone relief:)
Thanks for sharing that Mary. 🙂
Mary,
You mention hips, neck, skull. This is also my pattern, and I know the reason – mild scoliosis with a sacrum that is dysfunctional due to injured ligaments that connect the sacrum to the ilia/ hip bones.
Finding any drug that really helps would be amazing. Sure wish we had some serious structure/function research. Check out the videos on You Tube by Jerry Hesch.
So is it less effective than pregabalin or perhaps was pregabalin’s efficacy inflated?
I believe it was inflated and it causes weight gain.
IMC-1 is our next hope. It is believed the cold sore virus is the problem. http://me-pedia.org/wiki/Fibromyalgia#IMC-1
Hello everyone, I have a question – have anyone heard of or tried a 5-htp for improving mood and sleep while diagnosed with fibromyalgia ? I’ve found this article and it seem to be interesting and helping as well -> brain-feed.com/can-5-htp-help-with-fibromyalgia-symptoms If anyone tried it please let me know! thank you Bára
Hi Bara, Dr. Murphree uses 5-htp to help with sleep in FM – https://www.healthrising.org/forums/resources/enhancing-sleep-with-5-htp.250/ – https://www.healthrising.org/forums/resources/using-5-htp-to-boost-serotonin-levels-in-fibromyalgia-and-chronic-fatigue-syndrome.249/
I was one of the over 3,600 patients taking part in the Daiichi Sankyo global series of trials of Mirogabalin (DS-5565) in early 2016 – although at the time my Specialist and I had no idea which of the randomized treatment regimes I was taking.
For me taking 15mg twice daily of the trial drug was a miracle; I had forgotten what life could be like without the constant pain and fatigue of FM and suddenly I was back to my old self and no side effects.
Unfortunately at the end of the 13 weeks trial I ran back into the hard, brick wall of full blown fibro flare-up and it has been demoralising to realise just how life limiting FM is.
I had been keeping my hopes up waiting for the release of Mirogabalin, but now that has been taken away.
!….So sorry to hear that. I’m still shocked that the trial wasn’t a success. Hopefully the drug will surface again and you can get at. I’ve found high CBD/low THC cannabis oils helpful for pain by the way.
I was also taking part in this trial of Mirogabalin. I was surprised to hear about the disappointing results. This drug gave me a new life, it worked amazingly well! Fantastic to have energy to do whatever I want and without the pain!! I hope and pray that this drug will be available at the marked in the nearest future. I got really sick after the trial. I’ve tried a lot of different drugs, but nothing works as well as Mirogabalin.
I think this trial shows, that one drug works well for person A, another drug works well for person B. So I hope the company pays attention to all the positive results as well. I know that many other patients in Norway had great results too. A women who had been without work for 20 years, cam back to work after using Mirogabalin for about a month. That’s amazing!
So to everybody: if Mirogabalin comes to the market, TRY IT 🙂
Maybe you will be one of the lucky ones it really really have great benefit from it!
I was also part of that trial. Started late 2015 and was then eligible to get the guaranteed Miragabalin for a full year after the 13 week trial. It was a Godsend to feel normal again. I literally cried at my last clinical visit because I knew what I was going back to. No side affects at all for me either and my blood pressure was noral for the 1st time in years! I’m devastated now. I really had my hopes up that it would be available soon. God bless you all in this fight.
Quite by chance I saw a locum doctor who suggested I try low dose propranolol to help my fm symptoms.
I was very sceptical, what would a locum know? As it turned out, he knew more than my regular gp. Propranolol has made a significant difference to my energy levels and muscle soreness.
Great to hear and thanks for passing that on Tessa. You’ve got a smart practitioner. LD propanolol is a little-known but good option – check out this link https://www.healthrising.org/treating-chronic-fatigue-syndrome-mecfs/drugs-for-chronic-fatigue-syndrome-mecfs-treatment/propanolol-inderal-treating-chronic-fatigue-syndrome-fibromyalgia/ for more.
I am a long term sufferer of fibromyalgia and it is accompanied by chronic fatigue.
My pain control plan consists of strong painkillers, acupuncture and meditation with relaxation techniques.
very recently I had a letter from the Pain Services of the NHS declaring that they have deemed Acupuncture ineffective in dealing with chronic pain.
The letter included a three page list of Acupuncture practitioners in my area should I wish to continue this treatment.
I am very disappointed in this anomaly. NHS suggests I am now denied this treatment unless I go privately. Further it now denies contact with the NHS Pain Service,
Aiden Lucas
I was diagnosed with fibromyalgia for 3 years, and it was very painful some days. I was taken methocarbamol to relieve the pain. Sometimes it helps and other days it doesn’t. it was killing me for 3 years, doctor said there was no cure. So I tried to live with it and it wasn’t easy.My childhood friend introduced me to Dr George (Good health herbs home),Dr George fibromyalgia herbal remedy cured me within 6 weeks of usage ,am fibromyalgia free now 100%.