By Donna Gregory Burch
The fibromyalgia community received some bad news earlier this week when Tonix Pharmaceuticals Holding Corp. announced TNX-102 SL (trade name: Tonmya), a low-dose, sublingual form of cyclobenzaprine (Flexeril), did not achieve the primary goal of pain relief in its latest clinical trial. The company will no longer seek approval from the U.S. Food and Drug Administration for TNX-102 SL, one of three new pharmaceutical treatments in the pipeline for fibromyalgia.
Lack of restorative sleep is one of the primary symptoms of fibromyalgia, and TNX-102 SL showed great promise for improving the slumber of fibro patients. Its developers theorized that if fibromyalgia patients could get better sleep, then it may lead to pain relief.
However, in the latest trial, TNX-102 SL failed to meet the threshold for pain relief. A high rate of patient dropouts not due to the use of TNX-102 SL contributed to the trial failure.
Below is a short Q & A with Tonix’s CEO Dr. Seth Lederman about what went wrong with the recent fibromyalgia trial and the future of TNX-102 SL.
Can you give me an update on the TNX-102 SL trial for fibromyalgia? I read that it did not achieve the pain relief goal.
The preliminary results from our Phase 3 clinical study, AFFIRM, designed to evaluate the safety and efficacy of TNX-102 SL (cyclobenzaprine HCl sublingual tablets) in patients with fibromyalgia, showed that the drug did not meet the main goal of reducing pain in fibromyalgia patients by 30 percent or more over a 12-week period. However, TNX-102 SL did show statistically significant effects on pain when analyzed by other standard statistical approaches.
TNX-102 SL activity in fibromyalgia was cross-validated by two additional endpoints, Patient Global Impression of Change (PGIC) and Fibromyalgia Impact Questionnaire-Revised (FIQ-R). These endpoints assess global improvement and a range of fibromyalgia symptoms and function.
TNX-102 SL showed strong effects on improving sleep quality by the daily diary and the PROMIS sleep disturbance scale. The internal consistency of these results provides clear evidence of beneficial effect of TNX-102 SL for the treatment of fibromyalgia.
What’s next for TNX-102 SL?
Despite achieving clinically meaningful results from AFFIRM, we have greater clarity on the regulatory path forward in our PTSD [post-traumatic stress disorder] program. We will therefore discontinue the fibromyalgia program in order to fully focus Tonix’s resources on advancing our potential breakthrough PTSD program to Phase 3.
I’m assuming this is a big disappointment for the company. Your thoughts?
Our decision to focus on PTSD was ultimately a decision between two appealing Phase 3 programs. We don’t have the resources to take both the fibromyalgia and PTSD programs forward, and since each program will likely require two Phase 3 studies for FDA approval, PTSD seems like the better option.
In our Phase 2 AtEase study, TNX-102 SL 5.6 mg showed significant improvement in PTSD measured by the Clinician Administered PTSD Scale (CAPS). PTSD is considered a serious mental illness, which is one of the criteria for breakthrough designation. We believe TNX-102 SL has the potential to be granted breakthrough designation since military-related PTSD does not appear responsive to currently approved medicines.
This is also a big disappointment for the fibromyalgia community since there’s such a lack of effective pharmaceutical treatments. Any thoughts?
While the study did not achieve statistical significance on the pre-specified primary analysis – where all patients who discontinued for any reason were treated as non-responders – there is clear evidence of efficacy in AFFIRM. We are gratified to see, in AFFIRM, strong positive effects on sleep quality and other clinical outcomes that are important to this patient population, as highlighted in the FDA-sponsored Patient-Focused Drug Development meeting conducted in March 2014.
These findings validate our approach to developing a differentiated drug that targets sleep quality and acts beyond analgesia to improve multiple symptom domains of a complex and inadequately treated condition. When we started our program, sleep quality was not regarded as a potential target of therapy in fibromyalgia. By establishing and validating sleep quality as a potential target of drug therapy in fibromyalgia, we believe we’ve shown the way for us and other drug developers to a new class of medicines that target this mechanism.
Can you please elaborate on the impact of the people who dropped out of the trial had on the data?
There was an unusual disparity between the treatment and control arms in patient discontinuations unrelated to efficacy or tolerability–for example, a patient was moving to a different state so needed to discontinue the trial. There were 15 patients who dropped out in the treatment arm compared to three in the placebo group. This affected the responder rate, as drop-outs (like those moving out of town) were categorized as non-responders. In a responder analysis, you are penalized when people do not complete the trial. This directly led to the result we obtained, which was a near miss. If a couple of those patients had stayed in the trial, the results could have been different.
Is it possible that Tonix may re-pursue Tonmya for fibromyalgia at some point?
It is not possible in the foreseeable future as Tonix is now dedicated to moving forward with our Post-Traumatic Stress Disorder (PTSD) study, for which we hope to start enrolling patients in the first quarter of 2017.
There was an unusual disparity between the treatment and control arms in patient discontinuations unrelated to efficacy or tolerability. For example, a patient was moving to a different state so needed to discontinue the trial. There were 15 patients who dropped out in the treatment arm compared to three in the placebo group. This affected the responder rate, as drop-outs (like those moving out of town) were categorized as non-responders.
In a responder analysis, you are penalized when people do not complete the trial. This directly led to the result we obtained, which was a near miss. If a couple of those patients had stayed in the trial, the results could have been different.
Now it’s your turn? Are you disappointed that TNX-102 SL won’t be available as a treatment for fibromyalgia? Share in the comments!
Donna Gregory Burch was diagnosed with fibromyalgia in 2014 after several years of unexplained pain, fatigue and other symptoms. She covers news, treatments, research and practical tips for living better with fibromyalgia on her blog, FedUpwithFatigue.com. 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.