Tonix Pharmaceuticals will target long Covid-19 in a Phase II trial set to start in the first half of this year, CEO Seth Lederman says. The trial will investigate its trimodal receptor antagonist TNX-102, which is also in development for fibromyalgia and other sleep-related disorders.
The Phase II will likely run for 14 weeks, comparing daily doses of sublingual TNX-102 with placebo. Tonix typically runs studies with 400–500 patients, although the biotech has not yet finalised the long Covid-19 trial’s size, Lederman notes.
As a primary endpoint, Tonix is considering a measure of daily pain scores, which it used in past trials of TNX-102 in fibromyalgia, including the Phase III AFFIRM trial (NCT02436096), Lederman says. But the exact endpoint choice for the long Covid-19 trial will depend on ongoing discussions with the FDA, he notes. And the agency has not yet released any standardised guidance on long Covid-19 trial endpoints, he adds.
The trial will target the approximately two-thirds of long Covid-19 patients whose symptom profiles are consistent with the idiopathic condition fibromyalgia, Lederman notes. The fibromyalgia and long Covid-19 symptoms that overlap include fatigue, body pain, sleep problems, and brain fog.
TNX-102 primarily targets sleep improvement, which could translate to overall improvement in other facets of fibromyalgia and long Covid-19, Lederman explains. “Nobody really knows what causes fibromyalgia, but for years people have speculated that it might be a postviral syndrome,” he adds. “Our view on long Covid-19 is that it is either related to fibromyalgia or maybe a form of fibromyalgia.”
Drug development for long Covid-19, also known as post-acute sequelae SARS-CoV-2 infection (PASC), has seen a buildup of public interest over the past months. And at least four long-Covid-19 trial readouts are expected in 2022 that could shape the future of the therapeutic space. But the FDA has yet to release any official guidance on preferred long Covid-19 endpoints, which can make it difficult for trial sponsors to design studies, Lederman says.
Unlike Covid-19 antivirals and vaccines – which have straightforward trial endpoints like rate of infection, hospitalisation, and death – there are no universal symptoms for long-Covid-19, Lederman notes. The FDA is considering both global symptom measures and measures specific to the long Covid-19 symptoms that individual treatments target, he explains. In general, the FDA has moved towards patient-centric measures such as patient clinical global impression (CGI) scales, he adds.
“I’m pretty confident that we’ll reach an agreement with the FDA on the endpoints before the (data) unblinding,” Lederman says. “It’s just a question of how the FDA will want us to score it.”
TNX-102 is an antagonist of three receptors: the serotonin-2A (5-HT2A) receptor, alpha-1 adrenergic receptor, and the H1 histamine receptor. Targeting serotonin-2A could increase slow wave sleep (SWS), while targeting alpha-1 adrenergic could reduce sleep disturbances. Meanwhile, zeroing in on histamine-1 may decrease wakefulness. TNX-102 is also under development for post-traumatic stress disorder (PTSD), agitation in Alzheimer’s disease, and alcohol use disorder.
Long Covid-19 2022 Trial Completion Calendar
|Event||Company||Drug||Mechanism||Long Covid-19 Symptom|
|Phase II completion January 2022||Roche||Pirfenidone||Immunosuppressant that inhibits collagen synthesis, down regulates cytokine production, and blocks fibroblast proliferation||Pulmonary fibrosis|
|Phase II completion March 2022||AgelessRx||Low-dose naltrexon (LDN) and nicotinamide adenine dinucleotide (NAD+)||LDN is an opioid receptor antagonist; NAD+ is an oxidizing agent. Designed to have anti-inflammatory and neuroprotective effects||Fatigue|
|Phase II completion Q2 2022||Resolve Therapeutics||RSLV-132||Human biologic Fc fusion protein that prevents activation of the immune system via Toll-like receptors and the interferon pathway||Fatigue and brain fog|
|Phase II completion April 2022||Sorrento Therapeutics||PSC-04||Cell therapy that inhibits the inflammatory response, reduce damage of alveolar epithelial cells and endothelial cells, and repair lung function||Pulmonary symptoms|
|Phase II completion June 2022||Brain and Cognition Discovery Foundation||Vortioxetine||Selective serotonin reuptake inhibitor and serotonin receptor modulator. Enhances levels of serotonin, noradrenaline, dopamine, acetylcholine, and histamine||Cognitive defects|
|Phase II completion September 2022||Bod Australia||MediCabilis||Medical cannabis that downregulates stress-related signals involved in chronic inflammation and pain||Long Covid-19; to be detailed|