PDUFA Date of August 15, 2025 for NDA TNX-102 SL in Fibromyalgia
On December 23, 2024, Tonix Pharmaceuticals Holding Corp. (NASDAQ:TNXP) announced that the FDA assigned a Prescription Drug User Fee Act (PDUFA) target date of August 15, 2025 for a decision on the NDA filing for TNX-102 SL for the management of fibromyalgia.
There has not been a new therapy approved for fibromyalgia by the FDA since 2009 (Savella), with Cymbalta (2008) and Lyrica (2007) approved previously. Lyrica generated revenues in excess of $1 billion in the treatment of fibromyalgia before going off patent and in 2022 generated revenues of approximately $624 million for the treatment of fibromyalgia (EvaluatePharma). Thus, an effective fibromyalgia therapy, particularly one that has an improved safety and tolerability profile compared to the currently approved medications, has blockbuster potential since many fibromyalgia patients skip doses or discontinue treatment in the first few months of therapy. In addition, none of the currently approved therapies address the common symptoms of pain, poor sleep, and fatigue simultaneously.
The NDA filing for TNX-102 SL in fibromyalgia is supported by the positive results from the Phase 3 RELIEF and RESILIENT trials. For a full overview of the results from the RELIEF trial see our previous report here. Briefly, the following graph shows the results for the primary efficacy endpoint of the trial, the mean change from baseline in weekly averages of the daily diary pain numerical rating scale (NRS) scores. At week 14, participants on TNX-102 SL had a LS mean change from baseline of -1.9 units compared to -1.5 units for participants on placebo (P=0.01). The graph shows separation between TNX-102 SL-treated and placebo-treated participants at Week 14 and shows separation (P<0.05) at Week 5, Week 8, and Week 10 and continues consistently from Week 12 to Week 14.
For a full overview of results from the RESILIENT trial see our previous report here. Briefly, the following graph shows the primary outcome measure of reduction in pain over the 14-weeks of the RESILIENT trial. TNX-102 SL showed a rapid onset of action and separated from placebo for each week of the study. It exhibited a robust effect size of 0.38. The Week 14 least square (LS) mean (SE) change from baseline for TNX-102 SL was -1.82 (0.12) and for placebo -1.16 (0.12), with a least square mean difference from placebo of -0.65 (0.16) (P=0.00005).
Pre-commercialization activities are currently underway. Tonix’s commercialization unit currently markets Zembrace and Tosymra, which are both indicated for the treatment of acute migraine in adults. Thus, Tonix will not be establishing commercial operations for TNX-102 SL from scratch but will be building upon the infrastructure that already exists. Tonix also had a market opportunity analysis conducted by EVERSANA. Overall, the analysis found a high level of interest in TNX-102 SL among physicians who treat fibromyalgia patients that included a substantial dissatisfaction rate with the currently FDA approved therapies for fibromyalgia.
Positive Topline Results for Phase 1 Trial of TNX-1500
On February 6, 2025, Tonix announced positive results from the Phase 1 clinical trial of TNX-1500, the company’s next-generation anti-CD40L (also known as CD154) monoclonal antibody, which is being developed for the prevention of kidney transplant rejection and treatment of autoimmune diseases. Three cohorts were evaluated in the Phase 1 trial: Cohort 1 (n=6; 4 active, 2 placebo) was dosed at 3 mg/kg; Cohort 2 (n=10; 8 active, 2 placebo) was dosed at 10 mg/kg; Cohort 3 (n=10; 8 active, 2 placebo) was dosed at 30 mg/kg. TNX-1500 was infused intravenously over one hour on Day 1 followed by an antigen challenge with keyhole limpet hemocyanin (KLH) on Day 2 and Day 29. The results showed that TNX-1500 was well tolerated with the only treatment-emergent adverse event (TEAE) occurring in ≥ 3 participants among all TNX-1500 groups being aphthous ulcer, which occurred in one participant each in Cohort 1, 2, and 3. Each of those TEAE’s was rated as mild, possibly related, and resolved within 2-10 days. Two of the study subjects did not complete the study (one was lost to follow-up and one withdrew consent), however no TEAEs led to study discontinuation.
Pharmacodynamic results showed that TNX-1500 at 10 mg/kg and 30 mg/kg blocked both the primary and secondary anti-KLH antibody response. The mean antibody level at all timepoints (through Day 120) were below the limit of quantitation (400 mg/L). The 3 mg/kg dose of TNX-1500 blocked the primary response to KLH and reduced the peak secondary response by 69% relative to the peak response to placebo. The mean half-life of TNX-1500 for each cohort was: 3 mg/kg, 19.6 (9.29) days; 10 mg/kg, 37.8 (5.46) days; 30 mg/kg, 33.7 (4.83) days. We believe this will allow for once a month dosing.
There are a few other anti-CD40L products in development, including Sanofi’s frexalimab and Eledon’s tegoprubart. Results from a Phase 2 trial of frexalimab in patients with multiple sclerosis were published last year and showed that the drug generally favored a greater reduction in the number of new galadium-enhancing T1-weighted lesions at week 12 compared to placebo while also showing a favorable safety profile (Vermersch et al., 2024). In 2017, Sanofi and ImmuNext entered into an agreement to develop frexalimab in which total payments to ImmuNext could total $500 million. Sanofi’s CEO previously stated that frexalimab peak sales could exceed €5 billion.
Tegoprubart is currently being evaluated in a Phase 2 trial for the prevention of kidney transplant rejection. While we anticipate TNX-1500 having once-monthly dosing, tegoprubart has a shorter half-life (18-26 days; Perrin et al., 2021) and is being dosed once every three weeks in the current trial.
Tonix is planning to discuss the results with the U.S. FDA in an ‘End-of-Phase 1’ meeting, and once alignment is reached with the agency a Phase 2 study of TNX-1500 in kidney transplant recipients will be pursued.
Strengthening Management Team
On January 8, 2025, Tonix announced the appointment of Mr. Gary Ainsworth as Vice President, Market Access. Mr. Ainsworth joins Tonix most recently from Eversana Intouch, where he served as Managing Director, Head of Market Access and led efforts to optimize the company’s vast market access capabilities and services. In addition, Mr. Ainsworth has experience from various positions at Havas Gemini, Baxter International, and Roche Laboratories. His significant leadership experience and successful track record of building market access functions will be critical as Tonix works toward the potential commercial launch of TNX-102 SL in fibromyalgia.
On February 4, 2025, Tonix announced the promotion of Siobhan Fogarty to Chief Technical Officer. Ms. Fogarty has over 25 years of experience in pharmaceutical and biotech product development and has been with Tonix since 2016, most recently serving as Executive Vice President of Product Development. Her career includes stints at Elan Corporation as a formulation scientist, GlaxoSmithKline as a manufacturing strategist, and a consultancy firm, eMSc, she started to advise pharmaceutical and biotech companies in product development and implementation of a phased approach to quality. Her extensive experience and organizational abilities will be vital to the company as it nears the potential launch of TNX-102 SL for the treatment of fibromyalgia.
Financial Update
On February 7, 2025, Tonix announced a financial update for the company as of December 31, 2024. The company announced that the $11.0 million mortgage on its facilities has been paid off, thus Tonix currently has no long-term debt. Unaudited financial results for the year ending December 31, 2024 showed that Tonix had approximately $98.8 million in cash and cash equivalents due in part to approximately $30 million that was raised in January 2025 (which we estimate will be enough to fund operations into the first quarter of 2026), net cash used for the year ending December 31, 2024 was $60.9 million (compared to $102.0 million for the year ending December 31, 2023), capital expenditures for the year ending December 31, 2024 was approximately $0.1 million (compared to $29.1 million for the year ending December 31, 2023), net operating loss for the year ending December 31, 2024 was approximately $126.6 million, which included a non-cash impairment charge of $59.0 million, (compared to $116.7 million for the year ending December 31, 2023), and net revenue from the sale of Zembrace and Tosymra was $10.1 million (compared to $7.8 million for the year ending December 31, 2023). In addition, on February 5, 2025 the company enacted a 1:100 reverse stock split to raise its stock price over $1.00 to satisfy the $1.00 minimum bid price requirement for continued listing on the Nasdaq Capital Market. We estimate that following the reverse split the company has approximately 5.6 million common shares outstanding.
Conclusion
We look forward to the FDA’s decision for TNX-102 SL on or before August 15, 2025. TNX-102 SL was well tolerated in both of the positive Phase 3 trials, thus we anticipate the drug gaining approval in 2025. With the company’s commercialization team already marketing Zembrace and Tosymra Tonix has the infrastructure in place in which TNX-102 SL can be added, which we believe will help lead to a successful commercial launch, if approved. We are very encouraged by the results from the Phase 1 study of TNX-1500, and while we understand that the compound is early in development we believe it could have blockbuster potential in both prevention of transplant rejection and the treatment of autoimmune disease. Following the company’s financial update and reverse split we have made multiple adjustments to our financial model, including increasing the potential for TNX-1500. Our current valuation is $50 per share.
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