What is your perspective on the current landscape of new drugs for conditions like chronic pain, chronic fatigue, sleep disorders and PTSD?
The opiate crisis has mobilized scientists, biotech and government to unite to develop new drug treatments for brain disorders. These new products are being developed with special attention to non-opiate painkillers. This wave of innovation includes some drugs based on revived treatment concepts and other drugs based on entirely new concepts. Several of the new products in development precisely target counter-productive brain functions with refined formulations of established psychoactive or neurology drugs.
We are developing Tonmya or TNX-102 SL for fibromyalgia, which is a chronic pain condition. Tonmya is an investigational new drug based on a new sublingual formulation of cyclobenzaprine that delivers the active ingredient into the blood stream through the mucous membranes of the mouth, which is called transmucosal absorption. Cyclobenzaprine is the active ingredient is well established and originally approved by the FDA as Flexeril® for the short-term treatment of muscle spasm. Our new formulation is designed for a bespoke treatment regimen for long-term daily use at bedtime. Tonmya’s tolerability is supported by cyclobenzaprine’s long history of use with no recognized risk of abuse or addiction. We also observed no evidence of abuse in our clinical studies. We plan to file a new drug application with the FDA for marketing approval of Tonmya in the second half of 2024. Clinical development of new fibromyalgia drugs is a long and risky process, so there is a high barrier to entry. No new fibromyalgia drug has been approved since 2009.
We are excited for the possibility to be one of the new non-opiate drugs that represent the post-opiate-crisis wave of innovation.
Drug developers rushing to develop new non-opioid pain drugs needed to first recognize that chronic and acute pain are different problems and need different drugs. We are also excited that Tonimya is a promising candidate for chronic pain, which is a different problem than acute pain. Some of the new drugs for acute pain target NaV1.8. But NaV1.8 is not expressed in the brain and is not expected to be a target for fibromyalgia drugs., since the brain is believed to be the origin of fibromyalgia pain. Fibromyalgia is a common chronic pain condition with unique attributes. It was a recognition of fibromyalgia’s unique attributes that led to our tailored, or precision-medicine approach.
The development of new chronic pain drugs was hindered by the economic success of high-dose opiate drugs like Oxycontin, that were improperly promoted as treatments for chronic pain. The opiate crisis taught that opiate abuse and diversion can lead to widespread health problems, including addiction and sometimes fatal respiratory suppression. We are excited to be bringing forward a new treatment for a common chronic pain, which may be a larger and more intractable problem than acute pain.
Can you elaborate on the significance of Tonmya (TNX-102 SL) for conditions like fibromyalgia, Long COVID and PTSD, and its mechanism of action?
TNX-102 SL is designed to address fibromyalgia through a novel therapeutic approach. TNX-102 SL is designed to improve sleep quality, not quantity. Tonmya facilitates sleep quality in fibromyalgia by targeting four post-synaptic receptors associated with vigilance or alertness. In this way, Tonmya targets fibromyalgia’s characteristic sleep disorder, which is called “non-restorative sleep”. We hypothesized that non-restorative sleep exacerbates fibromyalgia symptoms and may be an obstacle to recovery. Tonmya’s statistically significant results in two potential pivotal Phase 3 fibromyalgia trials support the idea that targeting non-restorative sleep can lead to improvement in fibromyalgia symptoms beyond sleep. In addition to improving sleep, in Phase 3 studies, Tonmya treatment improved fibromyalgia’s characteristic widespread pain. Based on Tonmya’s results, we now recognize that fibromyalgia’s defining symptom of chronic pain may be inextricably linked with poor sleep quality. In the trials, Tonmya was well tolerated and the most common adverse events were local administration site reactions related to its sublingual delivery.
How does Tonmya distinguish itself from existing sleep medications on the market?
Tonmya differs from traditional sleep medications because in clinical trials, Tonmya improves sleep quality, but not quantity in fibromyalgia. We believe this may be a paradigm shift. Traditional sedatives or hypnotics increase sleep quantity that is measured by a decrease in “sleep latency” or the time to fall asleep. Other traditional sedatives increase sleep quantity measured by decreasing “wake after sleep onset”. In contrast, Tonmya aims to improve sleep quality, not quantity. Tonmya’s focus on enhancing quality of sleep has potential advantages for fibromyalgia patients. In clinical trials, Tonmya showed broad-spectrum symptomatic improvement in fibromyalgia. A previous study of the traditional hypnotic zolpidem showed no efficacy in fibromyalgia. For this reason, we believe TNX-102 SL is fundamentally different from traditional sedatives or hypnotics, which generally increase sleep quantity.
What are the prospects for Tonmya’s market availability, particularly for fibromyalgia patients, and what does this mean for the broader patient community?
We plan to file a new drug application with the FDA this year, and expect an FDA decision on approval next year in 2025. Fibromyalgia is a chronic pain syndrome that, in addition to widespread pain, includes the symptoms of fatigue, non-restorative sleep and cognitive dysfunction. Our Phase 3 program results suggest that the effect of Tonmya on sleep leads to effects on other core fibromyalgia symptoms such as pain and fatigue. These improvements across multiple symptoms suggest that Tonmya has the potential to improve fibromyalgia as a syndrome, an effect we call a “syndromal” improvement.
In the context of PTSD, how is Tonmya being explored for preventive applications, and what implications does this have for its accessibility and use?
We are collaborating with the University of North Carolina (UNC) on an innovative study to explore whether TNX-102 SL treatment administered immediately after trauma can decrease or prevent certain short and long-term effects of trauma. The short-term effects to be studied include “acute stress reaction” and “acute stress disorder”. We will also study whether TNX-102 SL treatment decreases the risk of posttraumatic stress disorder or PTSD. The rationale behind this approach stems from evidence suggesting that poor sleep quality after trauma is linked to a higher risk of PTSD. Therefore, we hypothesize that improving sleep quality after traumatic events may reduce the risk of developing PTSD. The planned study will be conducted by UNC under an investigator-initiated IND and funded by the Department of Defense. We expect enrollment to begin in Q2 2024. The trial will enroll people presenting to Emergency Rooms after a motor vehicle collision. After informed consent, patients will undergo randomization to receive either TNX-102 SL or placebo for two weeks. UNC investigators will assess whether early treatment with TNX-102 SL can reduce the short-term symptoms associated with ASR and ASD and decrease PTSD risk. The trial will study whether TNX-102 SL treatment improves sleep quality after trauma, and if so, whether TNX-102 SL might facilitate the processing of traumatic memories associated with the event. This preventative strategy represents a novel application of TNX-102 SL that underscores the importance of sleep quality in recovery from trauma.
