During the year following my fibromyalgia diagnosis, my rheumatologist prescribed five different drugs in an attempt to relieve my pain.
None of them worked.
The current fibromyalgia drugs on the market are notoriously ineffective. I remember my rheumatologist sharing a surprising statistic that I’ve since verified through my own research: The most effective fibromyalgia drugs provide at least a 50 percent reduction in pain in only about one-third of patients.
We desperately need better treatments, and drug companies are anxious to deliver them. Two new fibromyalgia drugs are currently in clinical trials, and a third one will be tested next year.
Two of these prospective treatments are cousins to drugs already on the market, and one takes a completely unique approach to fibromyalgia. I’ll start with that one first.
IMC-1: A blockbuster combo?
The U.S. Food and Drug Administration (FDA) has fast tracked IMC-1, a combination of famciclovir (Famvir), a common antiviral, with celecoxib (Celebrex), an anti-inflammatory arthritis drug, for a Phase III trial next year.
Dr. William “Skip” Pridgen, the combo’s discoverer, believes the HSV1 virus, commonly associated with cold sores, may be a culprit in fibromyalgia. He developed this theory while treating the gastrointestinal issues of fibromyalgia patients in his growing surgical practice in Tuscaloosa, Alabama.
Pridgen noticed patients’ symptoms seemed to wax and wane over time and speculated these flares may be caused by the activation of an undetected virus. He tested his theory by prescribing common antiviral medications and noticed some slight improvement among patients.
Around the same time, he began giving fibromyalgia patients samples of Celebrex, hoping the anti-inflammatory would reduce their overall pain. The patients who took both the antiviral and the Celebrex began reporting substantial improvements in their fibromyalgia symptoms.
In 2014, Pridgen and his research team conducted a phase II study involving 143 fibromyalgia patients at 12 U.S. clinics. Patients either received IMC-1 or a placebo. After 16 weeks, 37.9 percent of patients reported a 50 percent or greater reduction in pain. That’s slightly better than Cymbalta, the most effective of the three FDA-approved fibromyalgia drugs. Side effects were low, with more patients from the placebo group dropping out of the trial due to adverse reactions than those taking IMC-1.
“We had pain reduction levels that rivaled or were comparable to other fibromyalgia drugs,” Pridgen said. “It wasn’t just that we reduced their pain. In all the measures we looked at [including fatigue, anxiety, headaches, TMJ, etc.], we seem to have an impact overall.”
“We’re radically different [from other fibromyalgia drugs],” Pridgen continued. “Instead of just trying to reduce pain perception, we think we’ve discovered what is at the root cause [of fibromyalgia].”
Pridgen expects even better results from next year’s phase III trial because it will use the dosage he’s been perfecting in his practice for the past six years. Phase II used a lower, less effective dose, he said.
Phase III may enroll up to 1,200 patients at around 60 sites, some of which could be international. Several major pharmaceutical companies have already expressed interest in IMC-1, and a new drug could be on the market within three years.
Mirogabalin: A better Lyrica?
Millions of patients were thrilled when Lyrica became the first FDA-approved drug for fibromyalgia in 2007. But for many, Lyrica’s real-life performance didn’t live up to drugmaker Pfizer’s picture-perfect TV commercials.
Based on Pfizer’s research, only around 1 in 5 fibromyalgia patients experience at least a 50 percent or greater reduction in pain. And worst still, Lyrica is well known among those in the fibromyalgia community for its troubling side effects.
I know a few people whose lives have been changed by Lyrica, and I’m grateful for any treatment that helps – even if it only helps a small percentage of us. But at the end of the day, for most of us with fibromyalgia, Lyrica hasn’t lived up to the hype.
Japanese drugmaker Daiichi Sankyo is now testing what could be Lyrica 2.0.
Lyrica and Daiichi’s new drug, mirogabalin (aka DS-5565), both relieve pain by binding to the body’s calcium channels. For readers who love more technical explanations, Alyssa Dargento, Daiichi’s public relations director, explained how Lyrica and mirogabalin differ: “Like Lyrica, mirogabalin preferentially and selectively binds to the a2δ subunit of voltage gated calcium channel proteins, which may help to regulate how the brain processes pain signals. However, in vitro studies have shown that mirogabalin has a unique binding profile and long duration of action at voltage gated calcium channels.”
In simple terms, Daiichi believes mirogabalin works better and with fewer side effects than Lyrica, and it’s investing millions in clinical trials to prove it. In fact, part of Daiichi’s research effort will involve pitting Lyrica and mirogabalin head-to-head against one another in trials.
“The clinical efficacy of mirogabalin was studied in two phase II, multicenter, randomized, double blind, placebo and active comparator-controlled adaptive studies in patients with diabetic peripheral neuropathic pain (DPNP),” Dargento said. “These data provided proof-of-concept for mirogabalin as a potential treatment for DPNP and suggested that mirogabalin may have utility in other chronic pain conditions, including fibromyalgia.”
Daiichi’s global ALDAY research program includes three phase III studies, which will compare various doses of mirogabalin, Lyrica and placebo in fibromyalgia patients with the main goal of relieving pain. There also will be an open label safety study. (ClinicalTrials.gov includes information on these trials.)
These are huge studies involving some 4,000 fibromyalgia patients at around 800 clinical centers worldwide. Daiichi is still recruiting patients for at least one of its studies.
“The top line results for the ALDAY phase III clinical trials are anticipated in calendar year 2017,” Dargento said. “We plan to share the results from the clinical trial program in publications and at medical meetings in the future.”
(As a footnote to this section, I read last year that Pfizer is working on a time-released version. I reached out to Pfizer at least twice in an attempt to interview someone for this story, but no one responded to my requests.)
Tonmya: Better sleep = less pain?
Cyclobenzaprine (Flexeril) was the final drug my rheumatologist prescribed for me before we essentially gave up on pharmaceutical treatments for fibromyalgia. I still have an old bottle of it that I reach for at bedtime when I’ve had a particularly awful day. It doesn’t stop the pain; it just knocks me out so I don’t feel it.
Unfortunately, cyclobenzaprine’s sedating effect works so well that I can barely function the day after taking it. I rarely use it because it makes me groggy through midafternoon.
But I may revisit cyclobenzaprine when and if Tonix Pharmaceuticals Holding Corp. releases Tonmya (aka TNX-102 SL), a new sublingual formulation of cyclobenzaprine HCL 2.8 mg.
Some fibromyalgia specialists believe, at its heart, fibromyalgia is really a sleep disorder, and I’m sure there are more than a few patients who would agree. Restorative sleep can be hard to come by for those of us with fibromyalgia.
The purpose of Tonmya is to improve the sleep of fibromyalgia sufferers.
“We think that sleep improvements lead to improvements in pain,” said Dr. Seth Lederman, Tonix’s CEO. “Sleep is not just a symptom. Sleep quality is part of the problem. If you can improve the sleep quality, then you can improve the other symptoms.”
Tonix just recently finished enrollment for its phase III AFFIRM trial of Tonmya, which involves 500 fibromyalgia patients at 35 U.S. clinical sites. AFFIRM’s main goal is to relieve fibromyalgia pain by at least 30 percent.
Trial results are expected by the end of September. If all goes well, Tonmya could be available for patients in 2018.
Since Tonmya contains a lowered dose of cyclobenzaprine, daytime grogginess shouldn’t be an issue for most users. In a previous trial, more people experienced daytime sleepiness using placebo than Tonmya.
The drug’s sublingual form also means absorption is much faster than its predecessor – just three minutes for Tonmya versus 45 minutes for cyclobenzaprine. (Those of us who use cyclobenzaprine to escape from pain know all too well how brutal those 45 minutes of waiting can be.)
In the earlier trial, temporary numbness in the mouth was the most common side effect. About 50 percent of patients reported oral numbness, which disappeared within 30-45 minutes of using Tonmya.
“We don’t have an impression that it’s a side effect that would limit its use,” Lederman said.
Tonmya also is being studied in those with post-traumatic stress disorder.
TD-9855 – On hold
In 2014, Theravance, Inc. announced positive results from a phase II study of TD-9855, a norepinephrine and serotonin reuptake inhibitor, in patients with fibromyalgia. Not only did it relieve pain better than placebo, but it also improved fatigue – a quality that’s unique among the fibromyalgia drugs currently on the market.
Unfortunately, TD-9855’s use as a potential fibro treatment has been put on hold.
“Theravance Biopharma has shifted the development strategy for the program and has opted to focus on a different therapeutic target (neurogenic orthostatic hypotension),” said Tim Brons, executive vice president of Vida Strategic Partners, the firm that’s handling Theravance’s public relations effort. “The company believes this is a more viable commercial opportunity for the drug and is planning to conduct a phase II study.”