Milnacipran Hydrochloride

An FDA approval for Tonix Pharmaceuticals' Tonmya makes it the first new medication for fibromyalgia in more than 16 years. Tonix Pharmaceuticals was founded in 2010 to develop and bring to market a drug for fibromyalgia. Fifteen years later, the New Jersey company has accomplished its mission with the FDA's endorsement of a new treatment for the painful chronic condition. The U.S. regulator’s green light covers first-in-class Tonmya (cyclobenzaprine HCl), which Tonix formulated as a once-daily bedtime treatment taken under the tongue for rapid absorption into the bloodstream. Tonmya marks the first new medicine approved for fibromyalgia in more than 16 years.“I’ve been working on this particular idea for more than 25 years,” Seth Lederman, Tonix’s CEO and co-founder, said in an interview with Fierce. “It’s a very hard condition to study and that’s why we’re so excited to finally be at the end.”The approval came after market close on Friday, but in the last few days, Tonix’s share price has increased by more than 10% in anticipation of the approval. The first three non-opioid drugs for fibromyalgia—Pfizer’s Lyrica, Eli Lilly’s Cymbalta and AbbVie’s Savella—were approved in a rapid-fire span of 19 months starting in 2007. Since then, there have been no non-opioid advancements in the treatment of the disorder, which primarily affects women.As a tertiary amine cyclic, Tonmya offers a new mechanism of action by targeting the nonrestorative sleep associated with fibromyalgia, as opposed to treating symptoms of the disease. While anticonvulsant Lyrica reduces pain signals sent to the brain, serotonin-norepinephrine reuptake inhibitors (SNRIs) Cymbalta and Savella affect brain chemistry, relieving depression and anxiety.Tonix has had a bumpy ride in its development of Tonmya, with two phase 3 successes sandwiched around a late-stage failure in 2023 to relieve pain in patients with fibromyalgia-type long COVID.Facilitating the approval were the two successful studies, which included nearly 1,000 patients. Across both trials, Tonmya significantly reduced daily pain scores compared to placebo at 14 weeks, succeeding on the studies' primary endpoint. Additionally, a greater percentage of study participants taking Tonmya achieved a clinically meaningful 30% or better improvement in their pain after three months, when compared to placebo.The key advantage for Tonmya over other approved treatments is its sublingual delivery, which “is is designed to reduce pain quickly and durably with a tolerable safety profile," Andrea Chadwick, M.D., of the University of Kansas Health System, said in a statement accompanying Tonix's approval announcement. “Treatments that are processed through the liver can result in metabolites that could affect a medicine’s efficacy and safety over time,” she said.For now, Tonix plans to market Tonmya itself and will add 70 sales reps to its current staff of 10. Tonix also markets two migraine products which it acquired in 2023. The company has not yet announced what it will charge for Tonmya. “Our approach is to be flexible, see what works, what doesn’t work,” Lederman said during the interview. “We do believe that this could be—maybe should be—a big pharma drug. But we’ve also seen that the trend in the industry is that more and more—particularly in the [central nervous system] space—that companies have to launch the drug themselves.”The company will target the 3 million people in the U.S. who have been diagnosed with fibromyalgia. But a larger population awaits as epidemiology studies indicate that there are roughly 7 million others in the U.S. who have the disorder and who have not been identified.Developing TonmyaTonix’s approach to finding a treatment traces back 50 years, when Canadian psychologist Harvey Moldofsky suggested that fibromyalgia was more a sleep disorder than a pain issue.“It was an audacious proposal,” Lederman said. “But he was the inspiration for us to pursue sleep quality as a target of therapy. I do think that people with fibromyalgia will recognize that pain and sleep have a vicious cycle. It’s self-reinforcing: Bad sleep, worse pain. Worse pain, worse sleep.” Tonmya is a repurposed version of cyclobenzaprine, a muscle relaxant which Merck gained approval for in 1977. The company later tested it for fibromyalgia. While the molecule showed initial effectiveness for patients, cyclobenzaprine’s benefits faded over time and Merck discontinued the program.“Instead of looking at is as the glass is half empty, we looked at it as the glass is half full,” Lederman said. “We took that and said, ‘How do we engineer this and get something that will have durability?”Tonix did that by converting the treatment from a pill to a sublingual formulation. In 2010, Jazz Pharmaceuticals failed in its attempt to gain an FDA nod to treat fibromyalgia with its sleep treatment Xywav, which was later approved for narcolepsy and hypersomnia.The failures and triumphs have combined to shed more light on the often-misunderstood disorder, giving patients more reason to explore treatment options.“There used to be a thing, doctors saying fibromyalgia doesn’t exist, it’s just women complaining—all these kind of stereotypes, tropes if you will,” Lederman said. “At the [International Association for the Study of Pain conference] last year, fibromyalgia was the plenary session. Fibromyalgia has arrived and now we hopefully have a next-generation, first-in-class product to address it with better tolerability.”  

On October 16, Tonix Pharmaceuticals announced that it has submitted a New Drug Application (NDA) to the U.S. FDA for TNX-102 SL (Cyclobenzaprine hydrochloride). This non-opioid, centrally acting analgesic is designed for the treatment of fibromyalgia. In two Phase 3 clinical trials, TNX-102 SL demonstrated significant pain relief and was generally well tolerated. FibromyalgiaFibromyalgia is a common chronic pain disorder that affects individuals worldwide, with a prevalence rate of 2% to 4% in the general population. It does not present with visible clinical symptoms, and physical examinations only reveal increased sensitivity at specific "tender points" under pressure. Consequently, the number of people actually diagnosed with fibromyalgia is much lower. According to the classification criteria established by the American College of Rheumatology, diagnosis requires multiple tender points and chronic widespread pain. The disorder is characterized by the amplification of sensory and pain signals within the central nervous system, leading to chronic widespread pain, non-restorative sleep, fatigue, and cognitive dysfunction. Currently available treatment options are limited, and patients often express dissatisfaction with existing therapies. Fibromyalgia is complex, with symptoms divided into two groups: primary features, which include the most characteristic symptoms of fibromyalgia and are crucial according to the latest diagnostic criteria, and other common features. About TNX-102 SLTNX-102 SL's primary ingredient is a sublingual formulation of Cyclobenzaprine. Its mechanism of action involves interacting with multiple GPCR-class central nervous system receptors, including 5-HT2A, α1-adrenergic, H1, and M1 muscarinic acetylcholine receptors. By engaging these receptors, TNX-102 SL aims to improve non-restorative sleep in fibromyalgia patients. Administered sublingually, this medication is rapidly absorbed through the mucosa, bypassing the liver's first-pass metabolism and thereby reducing the production of long half-life active metabolites. Currently, three FDA-approved drugs are available for fibromyalgia, representing two distinct drug classes. These include gabapentinoids, with Pfizer's Lyrica® (Pregabalin) approved in 2008, and SNRIs, represented by Eli Lilly's Cymbalta® (Duloxetine) and Abbvie's Savella® (Milnacipran), approved in 2007 and 2009, respectively. If approved by the FDA, TNX-102 SL would be the first new tricyclic medication for fibromyalgia treatment. Clinical trial progress The NDA submission is backed by data from two 14-week double-blind, randomized, placebo-controlled Phase 3 clinical trials. Both studies showed that TNX-102 SL significantly reduced daily pain compared to placebo. The drug was generally well tolerated, with no new safety signals observed. TNX-102 SL has received Fast Track designation from the FDA, aimed at accelerating the review of important new drugs that treat serious conditions and address unmet medical needs. The FDA typically has 60 days to assess whether the submitted NDA is complete and eligible for review. If accepted, an approval decision is expected in 2025. "The submission of the NDA is a critical step forward in providing a new first-line treatment option for fibromyalgia patients," said Dr. Seth Lederman, CEO of Tonix. "TNX-102 SL will be the first member of a new drug class for treating fibromyalgia, and we believe it will offer patients a novel treatment choice." "Despite the availability of three FDA-approved drugs, there is still an unmet need for new treatment options for fibromyalgia," commented Dr. Gregory Sullivan, Chief Medical Officer of Tonix. "If approved, TNX-102 SL will be the first new tricyclic medication for fibromyalgia treatment." How to obtain the latest research advancements in the field of biopharmaceuticals? In the Synapse database, you can keep abreast of the latest research and development advances in drugs, targets, indications, organizations, etc., anywhere and anytime, on a daily or weekly basis. Click on the image below to embark on a brand new journey of drug discovery!