Despite a worsening pandemic, Tonix Pharmaceuticals Holding Corp., a clinical-stage biopharmaceutical company, is pushing ahead with a third – and hopefully final – clinical trial of TNX-102 SL, a sublingual version of the common muscle relaxer cyclobenzaprine (brand name: Flexeril), as a potential fibromyalgia treatment. If successful, TNX-102 SL could become available during 2023 as a new pharmaceutical option for fibromyalgia patients.
In 2016, a previous phase 3 trial, known as the AFFIRM study, using 2.8 mg of TNX-102 SL failed to meet the threshold for pain relief among fibromyalgia patients. But instead of giving up entirely on the potential of TNX-102 SL, Tonix launched two new phase 3 trials earlier this year using 5.6 mg in hopes the larger dose would have greater pain-fighting ability.
Results from the first of those two phase 3 trials, known as the RELIEF trial, are expected by the end of this year.
Patient recruitment is ongoing for RALLY, the other phase 3 trial using 5.6 mg. Fibromyalgia patients who are interested in participating in the trial should visit RallyStudy.com for more information.
While many pharmaceutical companies halted their clinical trials due to the COVID-19 pandemic, Tonix continued the RELIEF trial through the spring and summer and into the early fall. The final patients completed the 14-week trial last month.
As RELIEF was winding down, Tonix began recruitment for RALLY, which mirrors RELIEF with the same dosing and participant numbers. Tonix is hopeful that completing the identical studies back-to-back will help the company satisfy U.S. Food and Drug Administration (FDA) requirements and bring TNX-102 SL to market as quickly as possible.
“RELIEF was unusual because we continued to enroll [participants] during the onset of the COVID-19 pandemic,” says Seth Lederman, MD, Tonix’s CEO and chairman. “The FDA issued guidelines in late March for how to safely continue to study participants during the pandemic, so we adopted all of the FDA’s recommendations and continue to. … We were several months faster in recruiting [for RELIEF] than we had expected, and we think it was because the clinical trial sites didn’t have other studies going on. We were one of the only studies that continued.”
How the Pandemic May Be Affecting the Clinical Trials
Unfortunately, continuing RELIEF through the early days of the pandemic may have negatively impacted trial results. In late September, Tonix released the outcome of a pre-planned interim analysis from an independent data monitoring committee (IDMC), which recommended adding another 210 participants to the RELIEF trial. The recommendation to add patients is a sign that TNX-102 SL may not be performing as well as anticipated.
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“We’re already quite suspicious that there may have been an unwanted effect of the pandemic, and I don’t mean that people are getting sick from COVID. What I mean is that the stressful, terrifying time of the onset of the pandemic may have affected peoples’ situation in terms of their health and pain status,” Dr. Lederman says.
In other words, the added pressure and uncertainty of the pandemic may have increased patients’ pain levels, which in turn could have impacted their perception of how well TNX-102 SL was working.
There is good news, however. The IDMC could have labeled the RELIEF trial as “futile,” which would have meant TNX-102 SL was having little-to-no effect on participants’ pain levels. The fact that IDMC recommended adding more patients instead likely means the committee could see TNX-102 SL was benefitting trial participants and thought increasing enrollment could help to prove its efficacy.
Since the IDMC’s recommendations are nonbinding, Tonix made the decision to continue the RELIEF trial with the 503 patients that were already enrolled and began recruitment for the RALLY trial.
The company expects to announce results from RELIEF by the end of the year. “Depending on what we learn from that, we may increase the size of the RALLY study, or we may just decide that the RELIEF study was confounded by the COVID pandemic,” Dr. Lederman says.
If RELIEF fails to show TNX-102 SL as an effective pain reliever for fibromyalgia, Tonix is committed to doing a fourth phase 3 trial.
“I think that the circumstances of the pandemic are so extraordinary,” Dr. Lederman says. “A lot of other companies are having trouble with trials related to the pandemic. If RALLY is positive, then we will continue on, and it’ll just be a delay in the program.”
It’s been more than a decade since the FDA has approved a new drug for treating fibromyalgia, and patients are desperately in need of new solutions to manage chronic pain.
“We’ve been working a long time [on TNX-102 SL], but we are still passionate about it because we think the need is still great,” says Dr. Lederman, who used to treat fibromyalgia patients as a practicing physician. “We believe in the effects that we’ve seen and the tolerability profile of our drug [and] the mechanism of how it improves sleep. … We continue to think that these characteristics should make it a distinct alternative for people who are dissatisfied with their current medicines. Even if the COVID pandemic hurt the RELIEF study in some way, and RALLY is positive, we’re still going to soldier on and try as hard as we can to make sure this is available to people with fibromyalgia.”
Donna Gregory Burch was diagnosed with fibromyalgia in 2014 after several years of unexplained pain, fatigue and other symptoms. She was later diagnosed with chronic Lyme disease. Donna covers news, treatments, research and practical tips for living better with fibromyalgia and Lyme on her blog, FedUpwithFatigue.com. You can also find her on Facebook and Twitter. Donna is an award-winning journalist whose work has appeared online and in newspapers and magazines throughout Virginia, Delaware and Pennsylvania. She lives in Delaware with her husband and their many fur babies.