Tonix TNX-102 SL: Innovating Fibromyalgia Treatment in Development

In this interview, we sit with Seth Lederman, CEO of Tonix Pharmaceuticals, about their new drug in development for fibromyalgia, TNX-102 SL. Lederman discusses the strategic advancements of this innovative treatment and its potential impact in addressing fibromyalgia.

How could TNX-102 SL Transform Fibromyalgia Treatment for Patients?

TNX-102 SL is designed for long-term daily use at bedtime to target the distinctive sleep disturbance of fibromyalgia.  The overall clinical goal of TNX-102 SL therapy is to decrease fibromyalgia pain.  Decreased pain was the primary endpoint of our pivotal clinical trials that support FDA registration. In two 14-week Phase 3 trials, TNX-102 SL demonstrated a statistically significant pain reduction in fibromyalgia patients and was generally well tolerated.

Fibromyalgia is a chronic pain disorder. Therefore, only a durable reduction in pain can be considered a meaningful benefit to fibromyalgia patients.  A drug that provides only short term reduction in pain is not a meaningful benefit for this chronic condition. The active ingredient of TNX-102 SL, cyclobenzaprine, is also the active ingredient of an oral swallowed tablet product called, Flexeril® (cyclobenzaprine HCl tablets) that has been marketed since the 70s for short term use. The oral swallowed cyclobenzaprine product was previously systematically studied by Merck as a treatment for fibromyalgia, and it failed to provide any benefit beyond one month.  Based on these results Merck abandoned development of oral cyclobenzaprine for fibromyalgia.

Because the oral swallowed version of cyclobenzaprine was not effective beyond one month, we invented the novel sublingual formulation to address the deficiencies of the swallowed oral tablet.  The TNX-102 SL formulation extends the benefits of cyclobenzaprine therapy beyond the one-month limit of oral swallowed cyclobenzaprine. In two randomized, placebo-controlled trials, TNX-102 SL provided a statistically significant fibromyalgia pain reduction after 12 weeks of dosing at the 5.6 mg dose. 

Now, with a PDUFA goal date of August 15, 2025, TNX-102 SL is one step closer to potentially becoming the first new FDA-approved fibromyalgia treatment in over 15 years.  It is also expected to be the first of a new class of non-opioid analgesics, called tertiary amine tricyclics (TATs). If approved by the FDA, TNX-102 SL could mark a shift in fibromyalgia care—addressing a major unmet need for over 10 million fibromyalgia patients in the U.S., most of whom are women. Many of these fibromyalgia patients are dissatisfied with current therapies.

Moe Alsumidaie: Can you tell me about your approved medical products and their strategic importance?

Seth Lederman: We market two FDA-approved drugs for the treatment of acute migraine.  Both are novel reformulations of sumatriptan. Zembrace® is an auto-injector and Tosymra® is an intranasal spray drug-device combination product. Both products bypass the GI track and first-pass liver metabolism. Zembrace delivers sumatriptan subcutaneously and is an easy-to-use product in which the patient never sees a needle.  Tosymra employes the Intravail® technology to deliver sumatriptan into the blood stream intranasally with the efficiency of subcutaneous sumatriptan.  Other products employing the Intravail technology are neffy® (intranasal epinephrine), Valtoco® (intranasal diazepam), and Baqsimi® (intranasal glucagon) which have similar pharmacokinetic profiles to EpiPen®, Diastat® and GlucaGen® respectively. 

Tonix Medicines is the commercial organization that supports our drugs for treatment of acute migraine.  Tonix Medicines will be crucial for the launch of TNX-102 SL. We believe the our growing commercial team positions us to  introduce TNX-102 SL to the market in an efficient manner. We hope that our commercialization of TNX-102 SL will maximize its impact and utilization by patients and healthcare providers.

Moe Alsumidaie: How does TNX-102 SL differentiate from existing fibromyalgia treatments?

Seth Lederman: TNX-102 SL is the first member of a new class of drugs that we call, the tertiary amine tricyclic (TAT) class.  TNX-102 SL is designed to harness the properties of TAT cyclobenzaprine and decrease the effects of a secondary amine tricyclic (SAT) active metabolite called norcyclobenzaprine. We designed TNX-102 SL to enable the TAT to target the disturbed sleep in fibromyalgia. Previously, TAT drugs were used to treat major depressive disorder, but as the understanding of these drugs increased it was appreciated that they were largely prodrugs for SAT forms.  The TAT forms became less popular than SAT forms for treating depression because of side effects like somnolence.

Unlike Lyrica® (pregabalin), a gabapentinoid, or Cymbalta® (duloxetine), an SNRI, our TNX-102 SL drug works on four well-characterized post-synaptic receptors, that regulate sleep quality. Our new approach potentially addresses the fibromyalgia syndrome closer to the origins of the problem.  Fifty years ago, in 1975, Prof. Harvey Moldofsky asserted that fibromyalgia was either caused or exacerbated by a sleep disorder, that he called non-restorative sleep.  Using TNX-102 SL to target non-restorative sleep, we believe TNX-102 SL is targeting a pathological process closer to the root causes of fibromyalgia.  Compared to the FDA-approved treatments with mechanisms targeting more peripheral processes, we hope that TNX-102 SL may lead to broad-spectrum symptom improvement and ultimately better patient outcomes. 

Moe Alsumidaie: What are the considerations for TNX-102 SL’s long-term safety and efficacy?

Seth Lederman: Fibromyalgia is a chronic condition, and TNX-102 SL treatment resulted in statistically significant reduction in fibromyalgia pain in two Phase 3 studies over 14 weeks. The primary endpoint of the studies was pain reduction at the end of the study, which after more than 12 weeks is a measure of durable improvement.  Typically, FDA approval requires two adequate and well controlled studies, which for fibromyalgia have been studies of at least 12 weeks duration. 

Since 1977, the Flexeril oral swallowed cyclobenzaprine products have been available in the US and have provided a record of human use.  Flexeril and a later controlled release capsule, Amrix® are only indicated for short-term 2-3 week treatment of muscle spasm.  Muscle spasm is not related to fibromyalgia. However, some patients have been prescribed oral cyclobenzaprine off-label for long periods of time.  This off-label long term use provides a record of long-term cyclobenzaprine exposure.

Moe Alsumidaie: What strategic advantages does the FDA Fast Track designation offer for TNX-102 SL?

Seth Lederman: Fast track designation recognizes the unmet need of fibromyalgia and that FDA considers fibromyalgia a “serious condition”. TNX-102 SL was granted this designation in July of 2024. This designation underscores the potential importance of TNX-102 SL in treating fibromyalgia and highlights the potential impact of TNX-102 SL in meeting the needs of patients. We are committed to working closely with the FDA to bring this innovative treatment to market as soon as possible.

Moe Alsumidaie: How will you address competition from established treatments like Lyrica and Cymbalta?

Seth Lederman: While we expect TNX-102 SL to be indicated for first-line use, we also aim to win over prescribers and patients who are dissatisfied with existing treatments. Dissatisfaction often drives fibromyalgia patients to rotate between current drugs which provides an opportunity for them to try other products. Despite the availability of generic Lyrica and Cymbalta, the high patient dissatisfaction rate may provide patients and their prescribers, the opportunity to explore new treatment options. 

Following FDA approval, we plan to highlight the unique properties of TNX-102 SL, particularly its novel mechanism of action and focus on disturbed sleep, to differentiate it from existing treatments. By addressing the specific needs of fibromyalgia patients and offering a new approach to treatment, we believe we can compete in the market and improve patient outcomes.

Moe Alsumidaie: How will you leverage the evolving understanding of fibromyalgia in your marketing efforts?

Seth Lederman: Recent epidemiology studies indicate that fibromyalgia is under-diagnosed.  Only approximately 3 million U.S. adults are diagnosed and treated out of the approximately 10 million adults who suffer from fibromyalgia.  The recognition that fibromyalgia is a type nociplastic pain and fibromyalgia’s inclusion in the definition of Long COVID could increase the rate of diagnosing fibromyalgia . 

We believe that education may raise awareness about fibromyalgia’s impact and our treatment’s potential benefits. Appropriate diagnosis of fibromyalgia can spare patients unnecessary exposure to dangerous opioids and steer them towards FDA approved products for fibromyalgia.

Nociplastic pain was introduced by the International Association for the Study of Pain (or IASP) in 2017.  Nociplastic pain is recognized as the third type of pain, following the prior recognition of nociceptive pain and neuropathic pain. Nociplastic pain arises from altered pain perception without evidence of actual or threatened tissue damage.  In 2021, the IASP revised their classification of chronic pain further (as part of ICD-11) and found that nociplastic pain is associated with fibromyalgia, irritable bowel syndrome and chronic low back pain.

In addition, in 2024 the U.S. National Academies of Science and Engineering (NASEM) concluded that fibromyalgia was a “diagnosable condition” in Long COVID. This follows the latest thinking about chronic pain and fibromyalgia. Many years ago, fibromyalgia experts dispelled the notion that fibromyalgia was a diagnosis of exclusion.  In current thinking, fibromyalgia can – and should be – diagnosed in patients with other concurrent, or comorbid medical conditions.  In practice, physicians should think of “fibromyalgia and…”  That is a way of expressing that fibromyalgia is frequently comorbid with other medical conditions.

The evolving understanding of fibromyalgia as a nociplastic syndrome, and its comorbidity with other conditions including Long COVID provide insights into the evaluation and treatment of complex conditions. 

For example, rheumatologists often care for patients with fibromyalgia who also suffer from either rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) or osteoarthritis (OA).  Increasingly, rheumatologists are learning that exacerbations of symptoms in patients with RA, SLE or OA may be exacerbations of their fibromyalgia and not of the other conditions.  This distinction can be important therapeutically, because appropriate recognition of fibromyalgia flares can spare patients the exposure to excess doses of biologics or corticosteroids that are normally prescribed to manage flares of RA, SLE or OA.

We hope that better education of healthcare providers and patients with the latest research and understanding of fibromyalgia will lead to increased appropriate diagnosis and treatment of fibromyalgia.  This evolving understanding by key opinion leaders – if disseminated to practitioners – may enhance the recognition and treatment of fibromyalgia, ultimately improving patient care and outcomes. 

Moe Alsumidaie: What key factors will be crucial to position TNX-102 SL in the market successfully?

Seth Lederman: Education about fibromyalgia is crucial.  We perceive that fibromyalgia awareness has waned despite the news of public figures who have openly discussed their fibromyalgia diagnosis and related issues. We hope that better education of healthcare professionals will lead to additional recognition of, and earlier diagnoses of fibromyalgia in their patients.  

The availability of our TNX-102 SL drug might bring renewed attention to fibromyalgia. We hope to engage key stakeholders, including healthcare providers and advocacy groups, to build awareness for TNX-102 SL. By discussing the unique benefits of our treatment and how it may address the unmet needs of fibromyalgia patients, we aim to educate prescribers and patients about TNX-102 SL as a potential new treatment option.

Moe Alsumidaie: Is there anything else you’d like to add about TNX-102 SL and its impact?

Seth Lederman: Chronic pain is a significant driver of healthcare visits and disability.  Tragically, chronic pain is also an unnecessary driver of the ongoing opioid crisis. While opioids continue to have a role in the treatment of acute pain, such as post-operative pain, there is no scientific justification for using chronic opioid therapy for non-cancer chronic pain conditions.  

Despite that lack of any recognized scientific basis for using chronic opioids to treat fibromyalgia, an analysis of health care claims in the U.S. commissioned by Tonix showed that opioid prescriptions are approximately half of the prescriptions for patients within 18 months of a fibromyalgia diagnosis.  In addition, more opioid prescriptions were written for fibromyalgia patients than for all three FDA-approved fibromyalgia drugs combined.

Chronic pain often leads to opioid use, and providing effective non-opioid alternatives is crucial for reducing dependency and improving patient care. Non-opiate treatments for chronic pain, like TNX-102 SL for fibromyalgia, could be vital in addressing this public health issue. Our focus on fibromyalgia aligns with broader public health goals to mitigate opioid abuse.

By developing a novel, non-opioid treatment option, we hope to make a meaningful impact on the lives of fibromyalgia patients and contribute to the broader effort to address the opioid crisis. We are committed to advancing the understanding and treatment of fibromyalgia, and to improving the health and quality of life for those affected by this challenging condition.

We are committed to ensuring that TNX-102 SL provides a reliable and durable treatment option for fibromyalgia patients, addressing their chronic pain needs with a focus on safety and sustained relief.