Cyclobenzaprine hydrochloride

iStock, Deagreez In Phase III studies, Tonmya showed significantly superior analgesic effects in patients with fibromyalgia versus placebo. The sublingual pill also led to better clinical outcomes. After more than a decade of waiting for a new therapy, patients with fibromyalgia will now have access to an oral pill in the form of Tonix Pharmaceuticals’ Tonmya, which the FDA s igned off on this past Friday. Given sublingually—under the tongue—before sleep, Tonmya is a non-opioid analgesic designed to be quickly absorbed into the bloodstream. The New Jersey biotech expects to launch Tonmya in the U.S. in the fourth quarter of this year, addressing a market of approximately 10 million patients, according to its Friday release. Common fibromyalgia symptoms include chronic widespread pain and poor sleep. Two double-blinded, randomized and placebo-controlled Phase III studies supported Tonmya’s approval, providing evidence of efficacy across nearly 1,000 patients. A readout in April showed that the pill significantly lowered pain and improved clinical outcomes in patients with fibromyalgia versus placebo. Common side-effects, established from three late-stage studies, included mouth numbness, oral discomfort, drowsiness, fatigue, mouth pain and canker sores. Tonmya’s approval is a “landmark advancement” for patients with fibromyalgia, Tonix CEO Seth Lederman said in a prepared statement on Friday, noting that these patients often suffer from the “debilitating pain” that comes with the disease. “We are hopeful that effectively treating pain with Tonmya could help improve the lives of people with this chronic condition.” Tonix’s regulatory win for Tonmya comes as a pain powerhouse stumbles. Earlier this month, Vertex Pharmaceuticals announced that its next-generation pain medicine VX-993, an investigational NaV1.8 blocker, was unable to significantly ease pain after bunionectomy—a surgical procedure involving the big toe. The failure pushed Vertex to abandon its acute pain program for VX-993. Vertex’s Journavx, also an ion channel blocker, in January became the first acute new pain medicine in more than 20 years—and opened up a new non-opioid analgesic pathway for moderate to severe acute pain. Journavx has already emerged as one of Vertex’s top-performing assets. In the second quarter, it brought in $12 million , which, while a relatively small contribution to the company’s $2.96-billion topline, represents a 79% beat to the analyst consensus.

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.”