Positive Phase 3 Efficacy Data Bolsters Tonix Pharmaceuticals' Expectations For Phase 3 Confirmatory Trial In Fibromyalgia

The following post was written and/or published as a collaboration between Benzinga’s in-house sponsored content team and a financial partner of Benzinga.

Clinical-stage biopharmaceutical company Tonix Pharmaceuticals Holding Corp. TNXP announced late last year positive results for the first of two pivotal Phase 3 studies of its lead fibromyalgia drug candidate, TNX-102 SL. The company reported that the results from its Phase 3 RELIEF study revealed TNX-102 SL provided statistically significant daily pain reduction over placebo while also being well-tolerated by participants in the study.

“We are delighted with the results of our first positive Phase 3 study of TNX-102 SL for the management of fibromyalgia,” said Tonix Pharmaceuticals CEO, Dr. Seth Lederman. “RELIEF is the first of two studies that are required for approval by the U.S. Food and Drug Administration (FDA) and we are already enrolling participants in the second Phase 3 study, called RALLY. Interim results for RALLY are expected to be reported in the third quarter of 2021 and topline results before the end of 2021. If the RALLY study is also positive, we expect to be in a position to file a New Drug Application in 2022.”

With TNX-102 SL now in mid-Phase 3 development, Benzinga had the opportunity to speak with Dr. Lederman about the results of the first positive Phase 3 study and what they mean for TNX-102 SL as it looks to its potential entry into a fibromyalgia drug market that generated $10 billion in combined revenue between formerly patented drugs from Pfizer Inc. PFE and Eli Lilly and Company LLY.

Broad Spectrum Relief

The positive Phase 3 results cast a hopeful light on the prospects for TNX-102 SL as a potential treatment for fibromyalgia, a condition that affects roughly 10 million adults in the U.S.  Fibromyalgia is a complex and frustrating syndrome for those who suffer from it, with key symptoms being widespread pain and often non-restorative sleep and fatigue. Patients also report a range of other symptoms, including stiffness, depressed mood and anxiety, all of which impact overall health and decrease quality of life.

Among the array of encouraging takeaways from the positive Phase 3 study, Dr. Lederman highlighted that the Phase 3 RELIEF study showed activity in improving sleep quality and fatigue.  Together with pain, sleep disturbance and fatigue are the most common symptoms of fibromyalgia.  Dr. Lederman believes that activity in pain, disturbed sleep and fatigue can be described as “broad spectrum” activity.  “Fibromyalgia involves more than just pain,” Dr. Lederman said, “but disturbed sleep and fatigue may be reasons why fibromyalgia patients resort to taking more than one drug at the same time, a practice called ‘polypharmacy.’”

“One of the key findings of the RELIEF study is the activity of TNX-102 SL in the three predominant symptoms that fibromyalgia patients care about: pain, non-restorative sleep and fatigue. The primary endpoint showed an effect of TNX-102 SL on reducing pain, which is a factor for FDA approval. But we believe TNX-102 SL’s activity in non-restorative sleep and fatigue have the potential to differentiate this product from other available treatment options.”

Those results are encouraging for TNX-102 SL’s potential entry into the fibromyalgia market, which was formerly dominated by Pfizer and Eli Lilly, whose drugs Lyrica and Cymbalta, respectively, were their largest drug products by sales before they lost patent protection and were substituted by generics pregabalin and duloxetine. Another FDA-approved drug for the treatment of fibromyalgia, Savella from AbbVie Inc. ABBV, is still on patent.

According to Dr. Lederman, TNX-102 SL is a different class of medicine than the currently FDA-approved patented and generic versions of these drugs. There are currently two primary approved treatments for fibromyalgia; gabapentinoids that act through dulling neuropathic pain and serotonin–norepinephrine reuptake inhibitors (SNRIs) that function by increasing levels of serotonin and norepinephrine to better regulate an individual’s mood and energy.

As a tricyclic molecule, TNX-102 SL works by inhibiting four high activity receptors in the brain - the serotonin 2A receptor, alpha adrenergic 1A receptor and histamine H-1 receptor and M1 muscarinic receptor - which, when overactive, can cause an increased sense of pain and anxiety as well as disrupt healthy sleep patterns. This mechanism of action, along with the results of the Phase 3 RELIEF study, would make TNX-102 SL a compelling alternative to current treatments for individuals who either are not benefitting from or are unable to tolerate the existing drugs.

“We believe TNX-102 SL targets the sleep disturbance in fibromyalgia and that increased restorative sleep allows the body to heal,” explained Dr. Lederman. “The active ingredient in TNX-102 SL, cyclobenzaprine, has no recognized potential for addiction or dependence. In contrast, pregabalin is a schedule V controlled substance according to the Drug Enforcement Administration. Also, TNX-102 SL was well tolerated, and the most common side effect was tongue numbness that, in people who experienced it, was episodic, transient and self-limited. In contrast, pregabalin has issues with weight gain and many people cannot tolerate the therapeutic dose. Duloxetine and Savella are reported to have adverse events relating to the digestive system.  In the RELIEF study, we did not observe those kinds of side effects with TNX-102 SL.”

Expanding Patient Options

Dr. Lederman made clear that the results of the completed Phase 3 RELIEF study represent an important milestone for Tonix and the progress of TNX-102 SL toward its New Drug Application or NDA and potential approval by the FDA. While Tonix is a much smaller pharmaceutical company than Pfizer, Lilly and AbbVie, Dr. Lederman feels TNX-102 SL’s novel mechanism of action, broad spectrum activity and tolerability will represent potential key advantages.

These factors will be particularly critical in increasing awareness of TNX-102 SL to doctors and patients who may be dissatisfied with their current treatment regimen or seeking more tolerable alternatives. Dr. Lederman explained that fibromyalgia patients commonly work with their physicians and insurers to try different medicines through the prior authorization process, searching for more effectiveness or with better tolerability.

“The prior authorization form is a certification the doctor makes to the insurance company that the patient has tried and is not satisfied with existing, cheaper, and usually generic alternatives.” said Dr. Lederman. “We believe that if TNX-102 SL is FDA approved and available, then it may potentially be prescribed to patients who are dissatisfied with the current medications, because patients may work with their doctors to file prior authorization forms.” 

He continued, “This apparently was the case when Cymbalta and Lyrica were first introduced, which is why, as new branded products, they grew so rapidly, despite the availability of drugs like venlafaxine and gabapentin.  Venlafaxine and gabapentin were generic and off-label, because they were not FDA approved for fibromyalgia.  But because they are mechanistically similar to Cymbalta and Lyrica some would argue that these were less expensive alternatives.”

Dr. Lederman characterizes the complex pathology of fibromyalgia as a neurological condition originating in the brain and believes that new approaches to managing a fibromyalgia patient’s medical therapy are supported by insurers through the prior authorization process.

Potential Other Indications

As Tonix prepares for reporting the results of the confirmatory Phase 3 study for its lead fibromyalgia drug, the company is not ignoring the future potential of TNX-102 SL in other indications.

In addition to fibromyalgia, Tonix is developing TNX-102 SL for treating posttraumatic stress disorder, agitation in Alzheimer’s Disease and alcohol use disorder.  Tonix has active investigational new drug applications, or INDs for each of these indications.  Dr. Lederman believes that the proposed mechanism of improving sleep quality means that TNX-102 SL may be useful in these and potentially other conditions.  In general, Dr. Lederman believes TNX-102 SL may be useful when poor sleep precipitates, exacerbates or blocks the recovery of the condition.

Dr. Lederman hopes the results of the currently recruiting confirmatory Phase 3 study will establish TNX-102 SL’s efficacy as a fibromyalgia treatment.  Given its efficacy results in the first Phase 3 study, Dr. Lederman feels that TNX-102 SL has the potential to be applied to other chronic pain disorders originating from the brain that affect an individual’s sensory experiences, such as chronic fatigue syndrome and traumatic brain injury, which appear to be exacerbated by poor sleep.

He compared the effects of long-term TNX-102 SL treatment in fibromyalgia to repairing a broken thermostat. Dr. Lederman said, “If a thermostat sensor is broken and inaccurately signals that the house is too cold, it will keep heating the house until it’s too hot and uncomfortable to live in.  Similarly, the pain sensor in the brains of fibromyalgia patients inaccurately signals patients that their body is broken, making it painful for the person to exist in their own body. If a medicine could re-set this brain sensor to accurately reflect what is going on in their body, then such a person may get relief.” 

Dr. Lederman continued, “The broken sensor in the fibromyalgia brain can also be imagined as a broken filter.  Without a filter, the brain experiences a continuous fire of noxious pain, light, sound, taste and odor signals.  We believe a drug with the potential to restore function to this sensor or filter could dampen or put out this fire and open a pathway to treating fibromyalgia.”

The author of this piece does not hold shares of any of the companies mentioned. Redington, Inc. employees and members of their families may from time own an equity interest in companies mentioned herein.

The preceding post was written and/or published as a collaboration between Benzinga’s in-house sponsored content team and a financial partner of Benzinga. Although the piece is not and should not be construed as editorial content, the sponsored content team works to ensure that any and all information contained within is true and accurate to the best of their knowledge and research. This content is for informational purposes only and not intended to be investing advice.