All posts tagged Pridgen

Through the “Valley of Death”: Dr. Pridgen, Fibromyalgia and the Looming Trials

First there were the anecdotal reports – FM patients were not just getting better but some, and not just a few, were getting well using something entirely new – an antiviral protocol, of all things, created not by a pain specialist or rheumatologist but by a surgeon.

Aside from a few doctors in the U.S., no one was treating FM with antivirals and virtually no research had examined the role of pathogens in the disease. A PubMed search of fibromyalgia and herpesviruses pulled up just two herpesvirus studies – both done over thirty years ago.

Skip Pridgen fibromyalgia

Dr. Pridgen’s hypothesis that FM is a herpesvirus disease may be put to the test by the end of this year.

But here was Skip Pridgen, a Tuscaloosa surgeon, not just asserting that herpesviruses were the cause of FM, but that an unusual antiviral protocol consisting of a herpesvirus antiviral and anti-inflammatory with antiviral properties (celecoxib) was doing the trick.  Plus, he asserted that herpes simplex virus – a virus that has gotten no attention in FM’s sister disease, chronic fatigue syndrome (ME/CFS) – was the culprit.

Pridgen, who’s treated thousands of patients with gastrointestinal issues, came up with the protocol after he noticed that his FM patients with IBS seemed to get better and then relapse. Figuring that a herpesvirus might be responsible, he gave them a herpesvirus drug and was surprised that not only their GI but also their FM symptoms improved. When celecoxib had the same effect in FM patients with arthritis, the idea of a drug combo – IMC-1 – was born.

Pridgen and Carol Duffy – his research partner at the University of Alabama – believe the drug combo is effective because each drug inhibits the virus at different points in its replication cycle and they stop viral reactivation as well.  (Hitting a virus at multiple points is a strategy employed to stop HIV.)

Pridgen created a startup Innovative Med Concepts – and put together a pretty hot team (including a past Vice President of Pfizer) and some respected researchers for its Scientific Advisory Board (including Daniel Clauw and surprise, surprise former ME/CFS researcher Dr. Dedra Buchwald) and got a Phase II clinical trial funded and going. (Dr. Buchwald was a surprise because she was so darn conservative in her approach to ME/CFS…)

The clinical trials are where it gets really serious, though. For all the reports of Pridgen helping FM patients, they mean nothing to Pridgen’s hopes of producing an FDA approved drug. The trials are where the action is, and with the recent publication of Pridgen’s Phase II clinical trial in the Journal of Pain Research, we finally have something we can really get our hands around.

The Trial

A famciclovir + celecoxib combination treatment is safe and efficacious in the treatment of fibromyalgia. William L Pridgen, Carol Duffy, Judy F Gendreau, R Michael Gendreau. Journal of Pain Research 2017:10 451–460

Pridgen has been almost relentlessly upbeat in his assertions about the effectiveness of his new protocol and he and his co-authors don’t pull any punches in the title of their journal article which boldly states that “A famciclovir + celecoxib combination treatment is safe and efficacious in the treatment of fibromyalgia”.

Because the trial was distributed across twelve sites, it sampled a broad array of FM patients (and doctors). With 143 patients participating, it was a good size and was double-blinded (neither the patients nor doctors/researchers knew who got the drug or placebo), placebo-controlled 16-week study.

Six questionnaires were used to assess the drug combo’s effectiveness. The primary endpoint – the test the study really had to meet involved two questionnaires – a numerical pain rating scale (NRS) and a past week functional and symptom assessment questionnaire called the Fibromyalgia Impact Quotient (FIQ-R) score.

The first part of the FIQ-R asks how difficult it was over the past week to do things like walk continuously for 20 minutes, vacuum the floor, climb one flight of stairs, go shopping etc. The second part asks each patient to rate their pain, energy, sleep, depression, etc.

The study participants had to be off a variety of drugs (duloxetine, milnacipran, pregabalin, gabapentin, sodium oxybate, and opioids). Over ninety percent of the participants were women and their average age was 49.

Results

Functionality and Symptoms – The FM patients on the IMC-1 protocol showed a statistically significant improvement in their functionality and overall symptom scores on the FIQ-R test relative to the patients not on the protocol.  (The average patient showed a 2.2 point improvement on the eleven point scale.)  Functionality, symptoms and overall impact of FM all showed significant improvement on the drug.

Pain Assessment – Past 24 Hours – With regard to the other primary endpoint – the NSR measurement of pain, only when the data was subjected to “imputation” did the patients report statistically significant improvement in their past 24-hour pain. (Imputation analyses were used to account for missing data.)

IMC-1 was statistically significantly superior to placebo in most of the tests

IMC-1 was statistically significantly superior to placebo in most of the tests

Overall Improvement – Another test called the PGIC which asked patients about how much they had improved. Patients had to report that they were much or very improved to pass the PGIC test. About 35% of patients on the IMC-1 protocol reported they were much or very much improved at weeks 12 or 16 vs about 18% of those on placebo – a statistically significant result.

Another Pain Analysis – Responder analyses used to assess what percentage of patients received a 30-50% reduction in pain found that about 30% of FM patients reported a greater than 50% reduction in pain over the past 24 hours on the IMC-1 drug combo.

Fatigue – Two fatigue assessments (MFI, PROMIS fatigue short form) had differing results; the older MFI test showed no significant improvements in fatigue while the more recently developed PROMIS test showed that those on the drug combo received statistically significant reductions in fatigue.

Depression – The depression findings were intriguing given that one does not ordinarily link depression with herpesvirus infections. When the imputation analyses to account for missing data were performed, however, IMC-1 produced a highly statistically significant (P=0.003) reduction in depression. (This data was not in the published paper.) Since the HSV-1 virus hangs out in three different nerve ganglia in the body, knocking it down could conceivably affect many symptoms – including depression and anxiety.

Safety and Tolerability

With more patients off the drug than on the drug reporting side effects, the IMC-1 drug combo passed the safety test with flying colors. That finding was bolstered by the much higher dropout rates in the placebo arm compared to the drug arm.

The Phase II clinical trials reported on here is a proof of concept trial done to demonstrate that the drug probably works and is safe. Because these trials are also used to help manufacturers determine the best dose to use in a Phase III trial, Phase II trials are also more experimental.

The results were good but not spectacular. I asked Dr. Pridgen if he was satisfied with them. Considering that he felt that Innovative Med Concepts had a hand tied behind its back by the FDA he was:

Given that the FDA restricted our dose to that which we ultimately used, we were thrilled that we met statistical significance with our primary, secondary and even our exploratory endpoints. Being able to show statistically significant improvement in Pain, fatigue, depression, and a dramatic impact on IBS is truly unique. Honestly, I have never seen a proof of concept trial with this broad of an impact. Knowing that the recent toxicology results support our planned ideal dose, as you might imagine, we are incredibly confident in our Phase 3 trial. Dr. Pridgen

Pinpointing the Culprit

One of Pridgen’s and Duffy’s tasks includes demonstrating that herpes simplex one (HSV-1) – the virus they believe is responsible for FM – is, in fact, present. Pridgen reported that Duffy’s analysis of FM patients gut tissue is complete and that the data that emerged “far surpassed” their expectations. They are writing up the manuscript now.

Through the Valley of Death

Pridgen reported a couple of factors that may increase IMC-1’s effectiveness in the next trial. A higher dose will be used in the next trial and the screening process for the participants will be tighter to avoid the impact of confounding factors.

The huge Phase III clinical trials required for FDA approval are called the “Valley of Death” by some for good reason. Pridgen said that testing the drug combination – featuring two drugs that are already FDA approved – will require two 500-1000 person drug trials, each costing from $25-50 million. That’s on top of almost complete animal toxicology testing that’s been done and the large proof of concept Phase II trial.

Trials like that take some heavy lifting and Pridgen’s enrolled some top talent to get IMC-1 through the “Valley”. Rick Burch, the President of Innovative Med Concepts and the former Senior Vice President for Pfizer, oversaw divisions employing more than 6,500 employees and had a hand in launching Lyrica. As chief medical and safety officers, Drs. Michael and Judy Gendreau helped usher Savella to FDA approval.

Pridgen-IMC-1-valley-death

Pridgen hopes to get IMC-1 through the “valley of death” and into its final clinical trials by the end of this year

Pridgen reported that Innovative Med Concepts met with 14 companies (half pharmaceutical, half companies that could provide financing) at JP Morgan in January of this year. He expects the trials to begin in late 2017.

He’s confident enough of the drug’s success to expect to employ in the next trial what he stated was the toughest primary endpoint ever used in an FM drug trial – a 50% or more reduction in pain.

Will Pridgen’s approach revolutionize our understanding and treatment of fibromyalgia? Could FM really come to be viewed as a herpesvirus induced disease – and if it is – what would that mean for chronic fatigue syndrome?

Intriguing questions all. The rubber will really meet the road for surgeon turned drug developer and the many FM patients looking for better treatment options probably at the end of this year.

 More on Dr. Pridgen and His Approach to Fibromyalgia

Simmaron

The Pridgen Revolution? Dr. Pridgen on Bringing His Antiviral Approach to Fibromyalgia To Market

The Pridgen Revolution?

Almost three years ago, Dr. Pridgen threatened to turn the world of fibromyalgia treatment on its head. Few had connected fibromyalgia with viruses or even immune problems when Pridgen announced that a) FM is caused herpes simplex virus reactivation and b) that it could be treated with antivirals. Then he shocked a chronic fatigue syndrome community (ME/CFS) well acquainted with antivirals with his assertion that one antiviral drug was not enough.  (Pridgen believes the same process is going on in ME/CFS). Pridgen wasn’t done, though, instead of using the usual anti-herpes virus drugs he used an anti-inflammatory (Celebrex) that had antiviral properties as his second antiviral.

pridgen_skipPridgen was knocking down received wisdom at every turn. One would not have been remiss to think that he and his unusual protocol would, as other supposed cures have, disappear at some point, but he hasn’t.

Instead, touting his success with the drug combo, Pridgen embarked on the long and difficult task of bringing a new treatment to market. After joining up with a University of Alabama virologist, Dr. Carol Duffy, Pridgen formed a biotech company aptly named Innovative Med Concepts, hired an ex-Pfizer vice-president, put together a strong scientific board, raised the money for a Phase 2 trial, and embarked on toxicology testing.

The Phase II trial was successful enough for the drug combo to move forward. Then Innovate Med Concept got a break when FDA granted fast-track status to its IMC-1 formulation, allowing the drug combo to move forward as quickly as possible.  (Fast-track status is granted to serious diseases that have “substantial impact on day-to-day functioning.”)

Now comes the real work – raising money for some very, very expensive Phase 3 trials. It’s been about a year since we checked in. In an interview, I asked Pridgen how it was going.

The Pridgen Interview

The Phase II trial results were certainly quite good, but they weren’t spectacular.  How did the Phase II trial inform the Phase III trial and how will it be different?

We wanted to prove the concept first with a dose that we knew would be effective.  Additionally, we chose this lower dose, as it would allow us to begin without first performing the very expensive and time-consuming toxicology studies. We will be beginning the final 2 toxicology studies necessary to be Phase 3 ready, this month, and we expect to have these completed late this winter or in early spring 2017.

This was a year to prep for the big Phase III trials. How much money do you need to raise? Do you need to do one or two trials and how big does the trial or trials need to be? How much money do you need to raise?

Typically, two Phase 3 studies are required, the studies require 500-1000 patients per study, and these studies cost $25-50 million each.

One report suggested that some pharmaceutical companies have shown interest. Can you say anything about that?

drug-developmentWe have met with a dozen different pharmaceutical companies. All knew that we would be either forming a strategic partnership, or continuing the drug development ourselves once we near Phase 3 readiness. We will meet with these pharmaceutical companies to discuss a possible partnership at the upcoming JP Morgan meeting Jan 2017 in San Francisco.

We’ve seen a couple of high-profile Phase III trial failures recently. One may have been due to doctors misidentifying a side effect as something else and using a drug that interfered with the results. Another got excellent results in the Phase II trial but then didn’t meet its primary endpoint (but did meet some of its secondary endpoints) in the Phase III trial.  In another trial a very high placebo rate surfaced. What can you do to ensure that IMC-1 trial goes as well as possible?

We have actually been using a variant of this combination at my office for 2-3 years, so we are extremely confident in, not only its efficacy, but also know the combination is quite well tolerated and safe. Though providing the necessary optimal dose is incredibly time-consuming for the office staff, and complicated for the patients, we endure this hardship because of the dramatic improvement they experience.

Dr. Pridgen remains very, (very) confident in the effects of his protocol; he’s so confident that he anticipates raising the bar for the primary endpoint of his Phase 3 trials. Drugs have failed because they chose the wrong primary endpoint or too difficult of a primary endpoint, but Pridgen reports the study will use the most difficult primary endpoint to attain of any fibromyalgia trial to date:

Finally, because IMC-1 is so effective, we will use a primary endpoint that represents the highest bar ever used for any of the drugs previously studied for FM. We feel that this will negate to some degree the placebo effect.

We can see from studies and patient comments that the fibromyalgia population is pretty heterogeneous one. Some people do well on Lyrica – others do terribly. Low dose naltrexone works very well for some and others do poorly on it, etc., etc. The heterogeneity seen in the reactions to pain medications, in general, is pretty daunting. Is there any way you can target FM patients who are more likely to do well on the drug?

Again, Pridgen waxed confident in how efficacious this drug combination is. He believes his is the only protocol that gets at the source of fibromyalgia.

We believe IMC-1 is targeting the possible cause of fibromyalgia, not just modifying the body’s perception of pain.

Emedicine lists four antivirals (Famvir, Valtrex, Acyclovir, Penciclovir) used to treat herpes simplex infections. You’ve found that you need to add Celebrex to Famvir to get the best results in FM. Why do you think this is?

Penciclovir is not available in the PO form because it is not well absorbed, so it is a better topical agent.  Actually, Famvir turns into the active form, penciclovir, once it is acted on by human and viral enzymes. Celebrex is effective as an antiviral also. Herpes viruses are known to up-regulate the Cox-1 and Cox-2 enzymes to maximize viral activation. Though Celebrex (celecoxib) is known as a Cox-2 inhibitor, it actually has substantial Cox-1 inhibition.

viral-attack-cfsAre the herpes simplex infections harder in FM harder to get at than in other diseases? Do you need to reach into the central nervous system?

Essentially all adults have HSV-1, but we believe there is an immune defect in place in some patients, which results in an inability to force the virus into dormancy after an acute infection. In other words, patients with FM, have an ongoing HSV-1 infection, which we feel results in a chronic stress response. The meds can act centrally, however, the virus lives in the Trigeminal, and Nodose ganglia which are intracranial, but technically not in the CNS. The dorsal sacral root ganglia are the third major site (in the pelvis) where the virus resides.

Note: The herpes virus is known to hide out all three of these ganglia or cell bodies.

  • Trigeminal ganglia – is the largest and most complex of the 12 cranial nerves. The trigeminal ganglia provides sensations to the face and other parts of the head. It also sends signals that allow us to chew and even helps with balance. People with trigeminal neuralgia can experience high levels of pain when doing things like brushing their teeth or putting on makeup.
  • Nodose ganglia – are sensory ganglia or nerve cell bodies of the vagus nerve that are found near the top of the spine..
  • Dorsal sacral root ganglia – are associated with vertebrae in the pelvic area. The nerves emanating from them impact all areas of gut and pelvic functioning. In between bouts of genital herpes virus reactivation, the herpes simplex virus hides in these ganglia.

Like the other herpesviruses, almost everyone is infected with HSV-1, and when reactivated these infections can be pretty harmful. They’ve been shown to cause gastrointestinal and esophageal disorders, acute viral encephalitis, and approximately 25% of all genital herpes infections. Fibromyalgia is a bit different; it causes widespread pain, fatigue, sleep and sometimes mood problems as well as other symptoms- and is thought more of as a central nervous system disorder than anything else. Can you explain what the herpes simplex virus is doing differently in FM to cause this extraordinary range of symptoms?

The ongoing stress response affects nearly every system in the body. The immune response to this stress response over time affects sleep, mood, anxiety, thyroid, adrenal function, GI tract, HA’s and much more.

Dr. Duffy was reportedly writing up a paper on her gut findings. Can you tell us that the status of that is?

We have one last sample (of 60 total) to obtain to complete the study.

(At a conference Duffy was reported to find HSV-1 in 100% of FM gut biopsies and a protein found only in cells that are actively infected with HSV-1 in 80% of patients.)

With another year under your belt have you learned anything new treating FM using Famvir and Celebrex?

We have found that anything that was previously part of the functional somatic syndrome will improve on this treatment. At the risk of sounding like a snake oil salesman, we have patients who have chronic non-seasonal sinusitis, HA’s, brain fog, and even libido issues who swear by IMC-1.

Dosing – I also asked Dr. Pridgen about dosing information. He replied that the dosing information has to be proprietary right now. This is because pharmaceutical companies or other funding sources would not back a product composed of already approved drugs if the dosages were put in the public realm. Given the enormous costs of the Phase 3 trials, Pridgen’s drug combo would never make it to market without their backing.

That means FM patients will have to wait before Dr. Pridgen publicly reports on the appropriate dose. For many people this conversation is moot – their doctors would not prescribe antivirals now anyway. People seeing Dr. Pridgen or people seeing doctors in touch with Dr. Pridgen will obviously get the right doses.

If the trials are successful and the FDA approves the IMC-1 formulation everyone should be able to get a shot at these drugs.

Can you give us a timeline regarding the Phase III trial(s)?

They will start next year.

____________________________

For more on Dr. Pridgen’s antiviral approach to fibromyalgia:

Dr. Pridgen on Doses, Fixing Broken Bodies and Why the Next Fibromyalgia Trials Will Be Better

If Dr. Pridgen is right, his protocol for treating fibromyalgia could end up turning the medical world’s conception of FM (and perhaps even chronic fatigue syndrome) on its head. The first treatment trial had good results but they didn’t exactly turn the FM world upside down. Geoff Langhorne asked him about that in an interview a couple of months ago and I followed up with my own questions.

A confident Dr. Pridgen explained why the first trials result were good but not earth-shattering and why the next trial results will be better. First some background.

How it Happened

“It was never my intention to be involved in Fibromyalgia” William Pridgen

Pridgen didn’t start out to treat fibromyalgia – he was simply trying to get at what was causing the diarrhea/constipation and abdominal pain in his patients.  Both he and his mother – a virologist – recognized that the pattern he kept seeing –stubborn symptoms which got better with treatment then got worse, and then better and then worse – could reflect a virus getting reactivated, then knocked down, reactivated then knocked down. Throw in the fact that his patients gut problems typically got worse during stressful events and a herpesvirus infection became a viable option.

herpesvirus

The pattern of remission and then relapse, particularly, after stressful situation, suggested herpesviruses.

Pridgen started off giving a couple of his patients a single antiviral herpesvirus drug. The fact that some of the patients did get better encouraged him, but it was not until he combined it with the anti-inflammatory Celexicob (Celebrex) that he really began to see results.

The big surprise was that his patients were reporting relief from a whole panoply of other symptoms. Their fatigue, their headaches, their muscle and joint pains, their sleep problems, their difficulty relaxing – all were improved. By the time twenty or thirty patients had reported this he really began to take notice.

“Holy crud!” in the interview he stated, “I discovered something.”

He switched gears and began offering the drug combo to people with chronic fatigue syndrome and fibromyalgia. He lambasted the idea that fibromyalgia or chronic fatigue syndrome are difficult diagnoses to make. As soon as he knew what these illnesses looked like, he said, anyone working in his office could spot them immediately.

Fixing What’s Broken

Patients tended to sporadically improve early with the full effects showing up after about three months. He wasn’t just treating herpesvirus infections, however. Asserting that these diseases “break things”,  he also worked on their treatment resistant sinusitis, acid reflux, thyroid issues, insomnia, anxiety, and depression.

fixing what's broken

Pridgen asserted it’s necessary to fix what else is broken for his protocol to have full effect.

In fact, his first step was to figure out what was broken and fix it and then put them on the drug combo “. He said “if you’ve done a good job with the first half” then 12 to 14 weeks into the treatment program a “switch” often gets flipped with people feeling a whole lot better.

Geoff then asked a great question – would you characterize this as a cure or a successful treatment?  Pridgen stated that you can’t “cure” or eliminate viruses, but that he did feel that his treatment protocol was getting at the core of the disease. Note, however, that Dr. Pridgen did put that qualifier – “If you’ve done a good job with the first half” – in. It’s important to treat the depression or generalized anxiety disorder, symptomatic gallbladder disease, severe reflux and chronic nonseasonal sinusitis, etc. for his combination treatment to optimally work.

His protocol, he believes, is much more effective at symptom reduction than the drugs currently approved for fibromyalgia. He does not feel those meds get at the core of the disorder: his does.

Herpes Simplex Virus-1

The predominant virus he believes that is causing the pain in fibromyalgia is herpes simplex virus-1 (HSV-1). HSV-1 has been put in the “fever-blister” category; it causes some unpleasant symptoms and nothing more. Pridgen believes that view and the accompanying attitude of benign neglect towards the virus HSV-1 are disappearing.

HSV-1, it turns out, isn’t always so benign, after all. Yes, the initial infection is usually mild. And yes, essentially everyone, including healthy people, is exposed to and carries HSV-1 in their body.

neurons HSV--1

HSV-1 hangs out in the neurons. In susceptible people that could be a problem.

Like the other herpesviruses, however, HSV-1 persists in the body hanging out in the neurons. After the initial infection, HSV-1 is able, in some people, to become reactivated, travel up the axon of the neuron to the nerve centers – waiting to be reawakened by a stressor.

Studies indicate that  almost any stressor including colds, eczema, menstruation, emotional and physical stress, stomach upset, fatigue or injury can reactivate it. It can cause encephalitis and blindness, and some evidence suggests it’s associated with Alzheimer’s disease.

Vaccines for HSV-2, a close cousin to HSV-1, are being worked on. If HSV-1 does end up being the cause of fibromyalgia, Pridgen believes widespread HSV-2 vaccination could, just as vaccines have put an end to measles, chickenpox, hepatitis and other viral illnesses, help put an end to fibromyalgia. A vaccine, by the way, could also potentially help some people who already have fibromyalgia much like the shingles vaccine helps people with Varicella Zoster reactivation.

The First Trial

“We didn’t get a 60-70% efficacy, because it wasn’t our ideal dose and a lot of patients had other conditions they couldn’t get fixed in a trial like that.”

If you’ve been following the Pridgen story you’ve probably heard of people who’ve tried the Famvir/Celebrex combination who’ve done well and others who haven’t. Pridgen addressed the variability in results in his protocol by asserting that the doses aren’t set and that many of the participants had more than fibromyalgia to deal with.

The trial was less restrictive than most other phase 2 (FDA approved) FM trials where men or people with severe depression weren’t allowed to enroll. He said they pretty much let everybody with FM in.

He also stated that if the patients failed to commit to fixing the secondary problems they didn’t do as well. The FDA also required only one dose be used in the trial – and that dose was not their “favorite” one.

Fifty-three percent of the patients in the trial had at least a thirty percent reduction in pain. That’s a good but not great figure, but Pridgen noted that almost forty percent had at least a fifty percent reduction in pain – and that’s a very good figure for FM. Already their stats, he stated, may prove to be better than the three FDA approved drugs for FM – and he hasn’t been able to use the dose he ultimately intends to market. He stated that some of the world class experts on IMC’s scientific advisory board have said they had “never seen pain data like this” for FM before.

The Next Trials

The next phase three trials, though, will be slightly more selective as the fibromyalgia patients will not have as many “extra conditions”.

It’s going to take time to raise the money and then do two phase III trials – which can be run side by side. While there may be one dose that works best for the most people, Pridgen asserted that no dose is perfect for this variable population and they’ll probably do a dose-ranging study to get at the variability.

They’re trying to get FDA to fast-track the next trials. My guess is that patient enrollment will not be a problem; they expected it to take nine months to enroll the last study and they did it in three.

When asked how the phase three trials are coming Pridgen stated, “We’re moving as fast as we can….This is not an easy process.”

Confident

“I feel very confident that the next two trials will be far more impressive”.

Dr. Pridgen appears to be utterly confident he’s on the right track. He said he’s seen a 1,000 plus FM patients and an equal number of chronic fatigue patients.

recovery from fibromyalgia

Prigen asserts many people have gotten well using his protocol.

“If a patient does what we tell them to do and they jump through the appropriate hoops it’s unbelievable what happens to these people – they do so much better” Skip Pridgen

When the Blue Ribbon Project came to Tuscaloosa, it was the only place, he said, they saw people getting better.

He said he’s seen “countless” patients get well and go on with their lives, including very ill patients.  “I’ve had some tremendously ill patients who get their life back….get back to working again.”

They come from all over. He gets the protocol started and then refers them back to their physicians. His Canadian and Australian  patients have a good chance of continuing with the protocol because their physicians are more open minded, but the Brits often run into a wall so unless they can cross the Atlantic, presently they are receiving little support from their own medical profession.

Dr. Pridgen Talks

When do you expect the study to be published?

Dr. Carol Duffy is feverishly working on the manuscript and should be submitting it for publication this summer, hopefully in one of the premier pain journals.

How did you, a surgeon, end up treating people with gut problems?

Many general surgeons perform endoscopies in their practice of medicine.

How did you get the idea to combine the antiviral with an anti-inflammatory?

I was merely giving them a NSAID for their joint pains, and serendipitously noticed the two drugs when combined had unexpected benefits. I’d never heard of anti-inflammatories used to hit viruses before. Virologists have known for two decades, though, that NSAID had antiviral properties.

You presented a very different model of fibromyalgia at the Rheumatology Conference than rheumatologist are used to. I don’t know if anyone has looked at fibromyalgia as a herpesvirus disorder let alone treated people with antivirals. What kind of reception did your talk receive?

Lot’s of questions, none too difficult to answer and generally it was well received even if the attendance was not ideal.

neurons

Pridgen and Duffy believe three sites in the body may be particularly affected in fibromyalgia: the gut, the vagus nerve and the sinus area

I know someone who couldn’t tolerate the Famvir but did very well on Celebrex for six months when everything fell apart again.

There are other options, and if his physician had reached out to me, I would have given the physician everything they needed to help that patient.

What can you say about the gut tissue biopsy results?

The preliminary data was presented a little over a year ago at an international virology meeting, and for patients who have FM 100% of those patients have HSV-1 data in their biopsies and 80% have a protein that is found only in cells that are actively infected with HSV-1.

If HSV-1 is found in the guts of FM patients is it your guess that it’s probably reactivating elsewhere?

The vagus nerve is the nerve that controls the gut and the virus lives in its ganglion. We postulate that there are two other major sites, the sinuses, and the urinary bladder, that are also likely sites of chronic reactivation.

If it’s active in the gut would you expect to see an increased incidence of cold sores in FM?

Approximately 30% of the population suffers from cold sores. If you go to the innovativemedconcepts.com site you will be able to watch a couple of video’s that explain this better.

big fibromyalgia studies are next for Pridgen

Has Pridgen cracked at least part of fibromyalgia? Time will tell. The big studies are next…

You tried several different combinations of drugs and Famvir turned out to be the antiviral of choice for the fibromyalgia patients in your study. Do you have any idea why Famvir was more effective than the other drugs?

(Dr. Pridgen said that’s a trade secret for now.)

In your experience are people who improve dramatically able to get off the drugs and maintain their improvement for a considerable amount of time?

Absolutely not! The moment they stop the meds the next time they are severely stressed the condition returns. You can’t stop diabetes, hypertension, and cholesterol medications and you can’t stop these.

What is the timeline for the phase III study or studies?

Plans are underway for the near future.

 

Drug Combo in Pridgen Antiviral Fibromyalgia Trial Identified – Some Results Available

A lengthy article originating on the University of Alabama website and an  abstract presented to the American College of Rheumatology Conference indicates that the two drugs Dr. William “Skip” Pridgen and virologist Carol Duffy PhD used in their Fibromyalgia antiviral trial were Famciclovir, better known as Famvir and Celexicob, best known as Celebrex.

The report also indicates that  Duffy found only herpes simplex – 1 viruses (HSV-1) in the gastrointestinal tissues of the FM patients. Neither of these drugs nor this type of herpes virus have been commonly used or associated with chronic fatigue syndrome.

HSV-1

Duffy found only herpes simplex-1 viruses in the gut tissues of FM patients

We also learned Pridgen discovered the two drug combo similar to the way Fluge/Mella uncovered Rituximab in chronic fatigue syndrome – by observation. Suspecting that herpes viruses might be to blame for the gastrointestinal issues in his patients, Pridgen started them off on Famvir.  The drug helped but symptoms remained.

After Pridgen noticed much greater improvement in the symptoms of the patients also put on Celebrex for their arthritis he combined the two drugs – for everyone.

In the University of Alabama article, Duffy reported the improvement on the two drug combo was immense.

““The patients who took both drugs, however, came back and said everything was better. Their fibromyalgia was gone. Their chronic fatigue was gone. Their headaches were gone. All of these things had cleared up. When the first few patients approached him, he thought it was a fluke, but as more and more and more patients said the same thing, he knew it couldn’t be a coincidence.”

The Triad

That drug combo never been used in herpes virus infected patients before, but it made sense to Duffy. She knew that some herpes viruses  increase the production of COX-2, a pro- inflammatory enzyme. While Famvir stopped the herpes viruses from replicating, Celebrex weakened the viruses, making them “unstable”.  Since Celebrex also has some antiviral properties, the drug combo hit the virus in three ways.

Famvir

Famvir

Famvir – rarely mentioned in ME/CFS – was the antiviral of choice for Pridgen

Valtrex, Valcyte and Vistide are often used to treat herpesvirus infections in chronic fatigue syndrome but Famvir is rarely mentioned. (Dr. Dantini appears to use Famvir frequently to treat his ME/CFS/FM patients.)

One of the reasons may be that Famvir is mostly used to treat herpes virus infections such as herpes simplex virus, herpes simplex virus 2 (genital herpes) and herpes labialis that have not been typically associated with ME/CFS.

The Newcomer – Herpes Simplex

Duffy scoured the gastrointestinal tissues of 45 patients for a virus. In the end it wasn’t EBV, cytomegalovirus or HHV-6 that showed up, but herpes simplex virus-1 (HSV-1) – the very virus she’s been studying in her lab.  (That’s a little scary, but a technique called immunoblotting was used to ensure contamination had not occurred.)

Herpes simplex virus is best known for its ability to cause cold sores and genital herpes, but according to a Wikipedia article can also cause  herpetic whitlowherpes gladiatorumocular herpes, cerebral herpes infection encephalitisMollaret’s meningitisneonatal herpes, and possibly Bell’s palsy.

HSV-1

The group believes HSV-1 could be affecting many different tissues in FM and other disorders

HSV-1 can infect various organs in the body including the peripheral and central nervous systems, upper respiratory tract, and gastrointestinal tract. It may play a major role in Alzheimer’s. It’s able to deplete mitochondrial DNA. One article suggests herpes simplex virus may be better adapted to take advantage of poorly functioning natural killer cells than any other herpes virus.

The group believes HSV-1 may be responsible for fibromyalgia, irritable bowel syndrome, chronic fatigue syndrome and perhaps other disorders. A video on the Innovative Med Concepts website indicates the virus can attack the facial, gastrointestinal and pelvic regions and that it ultimately takes up residence in the vagus nerve.

It took Pridgen and Duffy about a year to raise the $4 million dollars for the 100 person plus phase II trial to assess the drug combo’s efficacy and safety.  Along the way they enrolled a member of the drug team that brought Savella to market in FM, and a past president of Pfizer in their effort at Innovative Med Concepts.  Noted FM researcher Daniel Clauw joined their advisory board.

Conference Abstract Provides Results

An abstract presented at the ACR conference yesterday suggested the drug combo produced strong improvement in some measures and not as strong improvement in others. The changes in pain using the revised Fibromyalgia Impact Form appeared impressive (p< 001) as did changes in function and symptoms (p<.004) and overall impact (p<.003). Fatigue was significantly improved but less so (p<.02).

stop-pain

Changes in pain were impressive. Fatigue was improved but not as much

However, only 33% of patients (vs 19% of those not on it) met the criteria for a secondary measure called the  Global Impression of Change Scale which asked about changes in a person’s activity, limitation, symptoms, emotions and quality of life. It‘s not clear how to parse the more impressive results in some of the tests with less impressive results in the last one.

The drug combination was judged very safe with more adverse events found in the placebo group than in the patients taking the drug.

Improving Efficacy Efforts Underway

If the trial wasn’t a complete win it nevertheless produced significant improvements in a notoriously difficult to treat illness.  Since fibromyalgia, like chronic fatigue syndrome, is believed to be a quite heterogeneous illness asking any drug or drug combo to be effective in everyone is unrealistic.

Phase III Trial Will Tell the Tale

tablets

Finding the optimum dose will be a key aim of the big trial

Designed to  assess basic aspects of efficacy and safety, Phase II trials are not the last word in efficacy. As the Pridgen/Duffey team proceeds to the Phase III trial  they’re exploring several ways to bump up efficacy. Duffy is working on diagnostic tests to identify which FM patients are most likely to benefit from the combo, and is doing toxicology tests to determine if higher doses are feasible. The optimum doses of the drug combo will also be determined in the Phase III trial. Expect efficacy rates to rise.

Big Trial Ahead

Next up is the big third phase trial – a jaw dropping $50-100 million trial the FDA needs in order to approve the drug combo for the treatment of fibromyalgia.

No one is satisfied with the state of fibromyalgia treatment – and few have looked to the immune system or to pathogens. If the results of this trial are not breathtaking – they are still very good –  and will hopefully improve as the therapy becomes better targeted.  They should begin to prompt a revaluation of what’s going on FM.

The publication of the study is probably just around the corner….

Brief Report From Dr. Prigden on the Fibromyalgia Antiviral Trial – and the Future Chronic Fatigue Syndrome One

It’s not too much to say that if successful, the Pridgen antiviral trials for Fibromyalgia would be a paradigm changer – turning FM from a poorly treated central nervous system disorder to a  disorder characterized by a (hopefully) treatable herpesvirus infection.

Is it a breakthrough? The results look good so far - stay tuned!

Is it a breakthrough? The results look good so far – stay tuned!

Pridgen’s approach is new in several ways. Not only has no one targeted herpesviruses in FM before, but the  herpesvirus Pridgen is targeting, herpes simplex virus, is one no one has connected with either FM or ME/CFS before.

Pridgen has also combined an antiviral with an anti-inflammatory (with antiviral properties).  Rumors have abounded regarding the identity or identities of the drugs, but we won’t know officially which they are until the report is made.

The fact that we haven’t had a press release by now regarding the Phase II trial has lead to some concern. (Phase two trials are typically larger trials (1-several hundred people) that further assess a treatment’s efficacy and safety. Pridgen’s Phase II trial was a large multi-center trial.)

I contacted Dr. Pridgen to see what he could say at this point. This is what he said.

  • They hope to present their research mid-Nov
  • A press release will predate that
  • The treatment was statistically significantly effective in improving nearly every primary and secondary endpoint
  • The treatment was significantly superior to placebo (p<.oo1) (not sure which  endpoints)
  • The treatment was better tolerated than placebo
  • The results in the FM trial are good enough that preliminary plans are being made for toxicology studies that will allow them to move forward on a similar Proof of Concept Phase 2 CFS (ME/CFS) trial; i.e. they’re beginning to work on a similar ME/CFS trial.
  • They will be looking for government/humanitarian funding for that.

The Earlier Video

Check out a confident Dr. Pridgen as he talks about the Fibromyalgia trial sometime around April at a local news station.

 

Conclusion

It’s going to take longer for the final results than many had hoped but the news otherwise is good.  The significant improvement in almost all the endpoints is promising (and I would say somewhat unusual).  The fact that they’re beginning preliminary planning for an ME/CFS trial suggests that the FM trial went well indeed.

Still, we won’t know how significant the significant improvements are until the press and study release probably in November.

That will be frustrating to those who want to get going on treatments now, but my understanding is that this period – prior to publication – is a delicate period in the development of any drug. If that’s true think how much more so it is for a startup company that’s going to need to raise significant funds for the  big Phase III trial.  Publicly releasing the full results and the drug combo they’ve identified this far in advance of publication would be a mistake.

For more on Pridgen’s antiviral trial check out