TLC Reports Positive Top-Line Results from Phase I/II Clinical Trial of TLC590 for Postsurgical Pain
TAIPEI, Taiwan and SOUTH SAN FRANCISCO, Calif.,
This randomized, double-blind, active-controlled, dose-escalation study evaluated the safety and tolerability of a single administration of TLC590 at four doses (190mg, 380mg, 475mg and 570mg) compared to a standard dose of ropivacaine (150mg, dose strength equivalent to 90mg bupivacaine) in 64 adult patients following inguinal hernia repair surgery. Ropivacaine is a standard-of-care local anesthetic used in the management of postsurgical pain which potentially confers less risk of cardiovascular and central nervous system toxicity than bupivacaine, another agent commonly used in the treatment of postsurgical pain.
The primary endpoint of the trial was safety, and key secondary endpoints included area under the curve (AUC) of numeric pain rating scale at various intervals from 0 to 96 hours, proportion of opioid-free patients, time to first postsurgical opioid use, and total opioid consumption. Top-line data showed that all four doses of TLC590 resulted in greater reductions in pain intensity than ropivacaine as measured by AUC at every interval. Moreover, the 475mg dose of TLC590 showed the following characteristics:
- There were durable, statistically significant and clinically meaningful reductions in pain intensity with movement compared to ropivacaine, as measured by AUC0-24h (p=0.0057), AUC0-48h (p=0.0131), AUC0-72h (p=0.0117) and AUC0-96h (p=0.0103); the greater levels of pain reduction was maintained through 168 hours.
- Through the entire duration of the study, 58.3% of patients who received TLC590 475mg did not use any rescue opioids at all.
- Among those who did use rescue opioids, time to first postsurgical opioid use was about four times that of the ropivacaine group (median 13.0 hours vs 3.3 hours).
- Mean total opioid consumption was 54% less through 96 hours post-surgery.
TLC590 exhibited dose-dependent activity based on blood concentration as well as pharmacokinetic markers. TLC590 was well tolerated, even at the highest dose, with a safety profile that is comparable to ropivacaine. Most treatment-related adverse events were mild, with most common symptoms being nausea, headache, vomiting and constipation; higher incidents of these mild adverse events were seen in the ropivacaine group. There were no serious or severe adverse events, no adverse events associated with potential local anesthetic systemic toxicity, and no adverse events leading to patient withdrawal.
"These results for TLC590 are quite remarkable. While an increased duration of analgesia was anticipated, the degree to which this was evident is noteworthy," commented Dr. Todd Bertoch, principal investigator of the TLC590 clinical trial. "This was in addition to the significantly improved analgesia compared to standard ropivacaine in the early postoperative period. These findings, combined with a favorable side-effect profile and the product's ease of administration, give great cause for optimism that TLC590 may be a formidable non-opioid tool for the treatment of both acute and long-term postsurgical pain in the future."
"The prolonged time to the first use of opioids is a promising indication that TLC590 may be able to help address the opioid epidemic that has become a worrisome crisis in the United States," commented TLC President George Yeh. "We look forward to further validating TLC590's potential to become a best-in-class treatment for postsurgical pain in our upcoming Phase II clinical trial in patients following bunionectomy, a type of hard tissue surgery in which often results in immense post-operation pain."
TLC590 is a non-opioid BioSeizer sustained release formulation of ropivacaine. TLC590 is designed to prolong the retention time of the ropivacaine around the injection site as a drug depot, to simultaneously extend its therapeutic period, and to reduce unwanted systemic exposure.
TLC (Nasdaq: TLC, TWO: 4152) is a clinical-stage specialty pharmaceutical company dedicated to the research and development of novel nanomedicines that maximize the potential of its proprietary lipid-assembled drug delivery platform (LipAD™). TLC believes that its deep experience with liposome science allows TLC to combine onset speed and benefit duration, and improve active drug concentrations while decreasing unwanted systemic exposures. TLC's BioSeizer™ technology is designed to enable local sustained release of therapeutic agents at the site of disease or injury; its NanoX™ active drug loading technology is designed to alter the systemic exposure of the drug, potentially reducing dosing frequency and enhancing distribution of liposome-encapsulated active agents to the desired site. These technologies are versatile in the choice of active pharmaceutical ingredients and scalable with respect to manufacturing. TLC has a diverse, wholly owned portfolio of therapeutics that target areas of unmet medical need in pain management, ophthalmology, and oncology. TLC is consistently ranked in the top 5% among all listed companies in Taiwan's Corporate Governance Evaluations.
Cautionary Note on Forward-Looking Statements
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements contained in this press release include, without limitation, statements regarding TLC's expectations regarding the clinical development of TLC590, the clinical benefits of TLC590 for postsurgical pain management, the timing, scope, progress and outcome of the Phase I/II clinical trial and planned Phase II clinical trial for TLC590 or any other clinical trials, and the anticipated timelines for the release of clinical data. Words such as "may," "believe," "will," "expect," "plan," "anticipate," "estimate," "intend" and similar expressions (as well as other words or expressions referencing future events, conditions or circumstances) are intended to identify forward-looking statements. These forward-looking statements are not guarantees of future performance and involve a number of risks, assumptions, uncertainties and factors, including risks that the outcome of any clinical trial is inherently uncertain and TLC590 or any of our other product candidates may prove to be unsafe or ineffective, or may not achieve commercial approval. Other risks are described in the Risk Factors section of TLC's prospectus dated
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