Tetrodotoxin (TTX), a selective voltage-gated sodium channel blocker, is the active ingredient in WEX Pharmaceuticals primary product under development, Halneuron®. A breakthrough in non-opioid analgesics, Halneuron is currently being evaluated in clinical trials for the treatment of a variety of pain conditions. In this series, we will be delving into TTX’s progress throughout these trials, as its efficacy in treating different types of pain is studied. In this article, we will be looking at a trial of TTX treating CINP.
CINP can be a debilitating condition. An unfortunate side effect of Chemotherapy-induced peripheral neuropathy (CIPN), CINP’s symptoms can affect between 10% to 80% of patients receiving cytotoxic chemotherapy treatments depending on the intensity and duration of the chemotherapy. As discussed in our previous article on the subject, while there are many medications that have been prescribed for treating CINP – including anticonvulsants, opiates, SSRIs, and NSAIDs – there is currently only one medication endorsed by the American Society of Clinical Oncology for treatment of CINP (Duloxetine), making any progress shown for other pharmacological options a potential breakthrough for CINP management. A drug trial regarding Tetrodotoxin’s efficacy as a potential treatment for CINP shows that TTX may be that breakthrough. Sponsored by WEX Pharmaceuticals, this randomized, double-blind, placebo-controlled study involved 125 patients with moderate to severe CINP, with an aim to evaluate multiple dose levels of TTX to find a suitable dose for subsequent trials.[1] The participants were split into five cohorts, with four each being administered a different dosage of TTX for a period of four consecutive days, and the fifth administered a placebo as a control group.
This study produced some key findings:
Reduction in pain:
Across the four TTX cohorts, patients that were administered TTX achieved a 30% reduction in pain severity within the first week of treatment, a reduction that was maintained at Day 28 in a significant number of patients. Overall, those who received TTX treatments were found to have reached peak pain relief around 3 weeks after starting treatment, with most patients not requiring additional rescue analgesics above their baseline.
Based on the study, it appears the TTX dose of 30 µg BID (30 micrograms twice daily) performed the best, resulting in reduction in pain that was significantly greater than the placebo. Members of this cohort were most likely to be responders with a ≥30% reduction in pain intensity at various time points. This dosing schedule has since been selected for further TTX trials.
Minimal side effects:
TTX was generally well-tolerated amongst all cohorts, and adverse events were largely mild to moderate. The most common adverse events related to TTX were oral paresthesia (tingling in the mouth) and oral hypoesthesia (numbness in the mouth). Serious adverse events were largely absent, and most patients recovered from their mild symptoms without any issues. This is an encouraging sign that TTX could be administered for CINP as a safe, tolerable alternative to existing treatments.
These results should be met with cautious optimism by people undergoing chemotherapy treatments. A 30% reduction in pain could make a vital difference for those suffering with CINP, potentially allowing patients to continue chemotherapy treatments at an optimal schedule. Considering the side effects that can stem from the medications often utilized to treat CINP, along with CINP’s origin as an unfortunate side effect of chemotherapy treatments, the tolerance and safety of TTX is a positive sign that a viable treatment for CINP may soon be on the way. Chemotherapy can be a life-saving treatment for people with cancer, and ensuring its side effects are curbed by safe, dependable analgesics should be a major priority. The success of TTX in managing CINP can be seen as a sign that progress is being made.
[1] Goldlust, S. A., Kavoosi, M., Nezzer, J., Kavoosi, M., Korz, W., & Deck, K. (2021). Tetrodotoxin for Chemotherapy-Induced Neuropathic Pain: A Randomized, Double-Blind, Placebo-Controlled, Parallel-Dose Finding Trial. Toxins, 13(4), 235. https://doi.org/10.3390/toxins13040235
DISCLAIMER:
Halneuron ® is still being developed and tested in clinical trials and has not yet been
approved for sale by Health Canada, the United States Food & Drug Administration (US
FDA), or any equivalent medical authority. This article contains forward-looking
statements and information under applicable Canadian securities laws (collectively
“forward-looking statements”), including statements regarding the safety and
therapeutic efficacy and utility of Halneuron ® and Tetrodotoxin (TTX) as a peripheral-
acting, non-opioid analgesic. Statements in this document regarding future expectations,
beliefs, goals, plans, or prospects constitute forward-looking statements that involve
risks and uncertainties, which may cause actual results to differ materially from the
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not statements of historical fact may be deemed to be forward-looking statements.
Without limiting the foregoing, the words “believes”, “anticipates”, “plans”, “intends”,
“will”, “should”, “expects,” “tolerates,” “projects,” “manages,” “reduces,” “shows,”
“promises,” “outperforms,” “affirms”, “acceptable”, “accepts”, “establishes”, “continued
advancement”, “in time,” and similar expressions are intended to identify forward-
looking statements. You are cautioned that such statements are subject to a multitude of
risks and uncertainties that could cause actual results, future circumstances, or events to
differ materially from those projected in the forward-looking statements. These risks
include, but are not limited to: those associated with the success of research and
development programs, the Company’s ability to raise additional funding and the
potential dilutive effects thereof, the regulatory approval process, competition, securing
and maintaining corporate alliances, market acceptance of the Company’s products, the
availability of government and insurance reimbursements for the Company’s products,
the strength of intellectual property, reliance on subcontractors and key personnel and
other risks detailed from time-to-time in the Company’s public disclosure documents and
other filings with the U.S. Securities and Exchange Commission and Canadian securities
regulatory authorities. Forward-looking statements are developed based on assumptions
about such risks, uncertainties and other factors, including, but not limited to: obtaining
positive results of clinical trials, obtaining regulatory approvals, TTX is a more potent
analgesic than standard analgesics, safety of product, effectiveness of drug, general
business and economic conditions, the Company’s ability to successfully develop and
commercialize new products, the assumption that the Company’s current good
relationships with third parties will be maintained, the availability of financing on
reasonable terms, the Company’s ability to attract and retain skilled staff, market
competition, the products and technology offered by the Company’s competitors, and the
Company’s ability to protect patents and proprietary rights. Forward-looking statements
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looking statements, whether as a result of new information, future events, or otherwise.
