Q&A with Dr. Seth Lederman, CEO of Tonix Pharmaceuticals Print E-mail
By BioMedReports.Com   
Thursday, 14 November 2013 09:59

Tonix Pharmaceuticals Holding Corp. (Nasdaq: TNXP) is a specialty pharmaceutical company developing novel medications for central pain disorders, including fibromyalgia (FM) and post-traumatic stress disorder (PTSD).

It is time for a Q&A on this company, which is one of the most intriguing biotech plays in healthcare. We spoke to Seth Lederman, M.D., the co-founder, CEO and chairman and Tonix, for his perspectives.


1. Your company is focused on treatments for FM and PTSD. What are the symptoms of these conditions?


While it may not seem like FM and PTSD are similar, they actually share a common symptom link—sleep. Because patients suffering from FM and PTSD can’t get a good night’s sleep, the symptoms of FM—including chronic diffuse musculoskeletal pain, increased pain sensitivity, fatigue, poor cognition, and mood disturbances—are exacerbated. We believe this is the same case for PTSD symptoms—widespread pain and sleep disturbances such as nightmares, night terrors, and difficulty falling or staying asleep.


2. What are some of the major drawbacks of current treatments for FM and PTSD?


With its large array of symptoms, FM has been notoriously hard to treat successfully. Patients are desperate for new options as they often report dissatisfaction with the current standard of care, which encompasses three FDA-approved daytime medications: the analgesic pregabalin, and the antidepressants duloxetine and milnacipran. As for opiates and prescription sleep drugs, they have proven largely unsatisfactory as treatments.


For PTSD, sertraline and paroxetine are the only FDA-approved products, but their efficacy is often modest and their use can be limited by side effects. Other anti-anxiety and sleep medicines have not been shown to improve either condition and have substantial safety concerns, particularly when used chronically.


3. Why do you think better sleep quality is the key to managing FM and PTSD?


It is significant to note that poor sleep quality—which has consistently been shown to be associated with both FM and PTSD—is not the target of any FDA-approved treatment for these conditions. Disturbed, unrefreshing sleep is a frequent complaint of patients with both FM and PTSD. In fact, at least three-quarters of FM patients report this symptom. Whenever sleep is perceived as restful, patients report substantial improvement in their daytime symptoms. So the key to truly effective treatment for FM and PTSD could lie in improving sleep quality. The National Pain Foundation estimates that 90 percent of FM patients have sleep problems; however, to date, no bedtime medication has been approved for this condition. Thus there appears to be an unmet need for a non-habit forming, safe, pharmaceutical treatment for FM and PTSD, perhaps one that focuses on improving sleep quality.


Ample evidence exists in the literature suggesting the potential of such an approach. For example, in October 2005, the National Fibromyalgia Association posted a detailed questionnaire on its website that was subsequently completed by 2,569 people (primarily Americans). The tabulated findings included a list of factors perceived to worsen FM symptoms; of the 22 factors listed, the third most frequent was sleeping problems (79 percent). In June 2008, the Fibromyalgia Global Impact Survey (a joint project of Pfizer Inc and the European Network of Fibromyalgia Associations) presented its final report, involving a survey of 800 patients and 1,622 physicians in eight countries (the UK, France, Germany, Italy, Spain, the Netherlands, Mexico and South Korea). The report included the percentage of respondents who judged whether each of 14 symptoms was “very/extremely disruptive to the overall quality of their lives.” An average of 70 percent of respondents across all eight countries listed “problems sleeping” as one such symptom. And among the findings of the REFLECTIONS study (Real-World Examination of Fibromyalgia: Longitudinal Evaluation of Costs and Treatment), reported by R.L. Robinson et al. in Pain Medicine in 2012, out of 91 physicians surveyed, 73.8 percent reported their FM patients exhibited sleep disorders.


Additionally, as noted by S. Roizenblatt et al. in Current Pain and Headache Reports in 2011, disordered sleep is such a prominent symptom in FM that the ACR included symptoms such as waking unrefreshed, fatigue, tiredness and insomnia in the 2010 diagnostic criteria for FM. The researchers further pointed out that compared with healthy control patients, most FM patients perceive their sleep to be of poor quality, reporting it as nonrestorative, and feel unrefreshed upon awakening.


Finally, a double-blind randomized placebo-controlled study on the effects of bedtime very low-dose cyclobenzaprine (VLDC) was conducted by Moldofsky et al. and the results were published in The Journal of Rheumatology in 2011. A total of 36 patients with FM were randomized and treated; the researchers concluded that bedtime VLDC treatment improved core FM symptoms including sleep quality. All of the studies summarized here lead to the idea that more restful sleep might be a key to treating both FM and PTSD.


4. Your company believes that its proprietary formulation of very low-dose cyclobenzaprine administered as a sublingual tablet (TNX-102 SL) may fill an unmet need. Can you tell us why?


For the reasons discussed above, we believe TNX-102 SL could prove helpful where existing treatments fall short. As you have noted, this novel treatment is based on cyclobenzaprine (CBP), a compound that has been FDA-approved as a muscle relaxant (Flexeril®) since 1977 for short-term use at higher doses but has off-label use as a slow-acting sleep aid in FM. We are testing our proprietary very low dose formulation of cyclobenzaprine, known as TNX-102 SL, administered as a sublingual tablet at bedtime, to determine whether it will decrease pain and improve other symptoms of FM and PTSD. It is designed for ease of use to optimize adherence.


5. Can you briefly summarize the mechanism of action for TNX-102 SL, and why this makes the treatment a viable alternative to existing treatments?


CBP works in the brain, and we believe its principal action in FM is via its interaction with receptors that are known to affect sleep quality. Our TNX-102 SL tablet is placed under the tongue where it quickly dissolves and releases CBP. The CBP is absorbed directly across the mucous membrane in the mouth into the patient’s bloodstream. TNX-102 SL is designed to be taken at bedtime, so as to begin to work as the patient falls asleep. The low dosage is tailored to be sufficient for efficacy yet minimize next-morning grogginess. We believe TNX-102 SL taken at bedtime will provide benefit to the quality of these patients’ sleep, and in turn improve their pain and other symptoms. Again, we demonstrated these effects in our Phase 2 study, yet with a primitive, un-optimized oral form of CBP. We expect TNX-102 SL to enter an efficacy and safety trial in FM in 2013; if successful, it can be considered as a pivotal study to support the marketing application. As a Serotonin and Norepinephrine Receptor Antagonist and Reuptake Inhibitor (SNARI), TNX-102 SL has a unique mechanism among other FM products, in that it targets both poor sleep and pain.


6. How does a small biotech like yours distinguish itself from potential competitors? Is showcasing your drug’s economic value for both patients and prescribers a key goal?


We believe the market for FDA-approved FM and PTSD treatments is underserved and that there is a need for new treatment options, since many prescription drugs provide relief only to some of the affected patients, only to some of some patients’ symptoms, or provide relief only for limited periods of time. We believe that if TNX-102 SL won FDA approval, it would be an appealing option because it has an entirely different mechanism of action from the currently approved products and we expect TNX-102 SL will be unique with regard to its use at bedtime. FM is an expensive condition, as patients suffer disability and absenteeism, apart from taking a variety of medications which may not be providing much benefit. We believe managed care is motivated to support a product that can decrease large expenses elsewhere in the system. 


7. If approved by the FDA, do you anticipate that your treatment will change the standard of care for FM and PTSD?


It would be much too bold for us to claim that TNX-102 SL alone could change the standard of care for these conditions, though it would bring another option—one that is unique and non-addictive—to patients who need it. It might also, however, alter the sequence of treatment for patients with the symptoms associated with them. If TNX-102 SL can be shown to alleviate the symptoms of FM or PTSD more effectively than the currently accepted first line of treatments, it could become the new first line of treatment. Many practitioners, including thought leaders in fibromyalgia, have adopted off-label cyclobenzaprine, and often use this ahead of the approved therapies. They will have their patients split oral tablets into pieces and take them a few hours before bedtime, so they look forward to a true bedtime product developed for this indication. We believe that as medical researchers and clinicians come to understand more widely the potential of addressing quality of sleep as a key to addressing FM and PTSD, the stage will be set for an evolution in care.


8. What are some of the upcoming milestones for 2013?


We’ve reached a lot of milestones thus far. We recently listed on the NASDAQ and completed a capital raise. We have also started the first of two double-blind registrational clinical trials in FM, called BEdtime Sublingual TNX-102 SL as Fibromyalgia Intervention Therapy (BESTFIT). Topline results from this first trial are expected in the second half of 2014. We are also expecting to begin a proof-of-concept trial of TNX-102 SL in PTSD in 2014.

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