On February 27, 2020 Sorrento Therapeutics, Inc. (Nasdaq: SRNE, "Sorrento") reported that an interim analysis of an ongoing Phase 1b study of resiniferatoxin (RTX) administered via epidural route in patients with intractable cancer pain has generated positive data (Press release, Sorrento Therapeutics, FEB 27, 2020, View Source [SID1234554898]). The study is completing enrollment of an additional 25 ug expansion dose cohort. Based on full study results a dose will be selected for RTX to proceed to Phase 3 pivotal trials in patients with advanced cancer pain.
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Safety in the higher dose cohort is expected to be supportive for testing RTX epidural administration in other advanced non-cancer disease related unmet clinical needs (with a choice of starting dose at 15 or 25 ug depending on the indication considered).
Results as planned in the original study (to 15 ug) are being presented at the American Academy of Pain Medicine Annual Meeting on February 27, 2020.
The Phase 1b open-label study was used for dose escalation to assess the safety and preliminary efficacy of a single epidural administration of resiniferatoxin for the treatment of intractable pain due to cancer. Initial expectations for safety and efficacy have been met for the Phase 1b study, though optimal dose selection will follow assessment of the additional dose group in which 25 ug is also being evaluated. Thus far, after Institutional Review Board approval was obtained, and with oversight by an independent data monitoring committee, data is available from 14 subjects with intractable cancer-related pain who received a single epidural injection of RTX from 0.4 to 15 ug.
Safety Outcomes
No dose limiting toxicities or notable adverse events unrelated to progression of underlying disease were encountered for any of the subjects. The most common treatment-related adverse event was transient post-procedural pain: 7 of 14 subjects (50%) reported moderate severity. Two additional treatment-related adverse events of moderate severity were back pain and increase in blood pressure in a patient. All events resolved in less than two days following drug administration.
Efficacy Outcomes
The ongoing trial will follow subjects for at least 84 days. The lower doses of 0.4, 1.0, 2.0, 4.0 ug did not demonstrate notable pain relief, but permitted dose escalation to the next designated dose level based on how well the drug was tolerated.
Three patients had marked pain relief starting shortly after initial administration that were still observed weeks after treatment: 1 of 3 subjects who received 8 ug (a 58-year-old woman with gastrointestinal stromal cancer with severe lower back pain reported a decrease in numerical pain rating scale (NPRS) scores from >6/10 to 2/10), and 2 of 3 subjects who received 15 ug (a 62-year-old man with rectal cancer noted significant improvement in pain, physical strength, mood, and appetite with NPRS scores reduced from 7-8/10 to 3/10; and a 57-year-old man with multiple myeloma and severe pain in his back, hips, and lower extremities subsequently reported mild pain in the target areas after RTX injection). Improvement in pain and mobility within 24 hours of dosing in the three responders at the higher dose levels of RTX suggests the clinical potential of the drug for intractable cancer pain.
Sorrento intends to present the detailed results of the completed study upon completion of the additional expansion cohort later this year. A pivotal Phase 3 trial is being planned using epidural RTX for severe pain states associated with advanced disease.
"We are encouraged by the benefits of using RTX to treat intractable pain in patients with metastatic cancer," said Associate Professor of Anesthesia, Srdjan S. Nedeljkovic, M.D. from the Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women’s Hospital at Harvard Medical School. "Even in patients with high levels of pain, RTX given via an epidural injection has been found to reduce pain intensity without having any long-term adverse safety consequences. The addition of RTX to existing cancer pain therapies represents a positive step forward in improving the care of patients with intractable cancer pain and offers the hope of enhancing the overall quality of life experienced by this population."
For access to the scientific presentation (AAPM poster) please visit
View Source
About Resiniferatoxin (RTX)
A thousand times "hotter" than pure capsaicin (16 Billion Scoville units versus 16M), and with a high affinity for afferent pain nerves, resiniferatoxin binds to TRPV1 receptors and selectively ablates the nerve endings responsible for pain signals experienced by patients1. Delivered peripherally (into the joint space) the transient nerve ending ablation effect can have profound clinical benefits lasting for months to years (as shown in canine studies2).
RTX-001 is a multicenter, open-label dose escalation Phase 1b study to assess the safety and define the maximally tolerated dose of resiniferatoxin administered via the epidural route for the reduction of moderate to severe pain signal intensity associated with advanced cancer. The Phase 1b study is a dose-escalation protocol in which cohorts of patients receive increasing doses of resiniferatoxin until the maximum tolerated dose is achieved. The primary objective of the study is to evaluate the safety of resiniferatoxin and identify the recommended Phase 3 dose. The secondary objective is to assess the preliminary efficacy of resiniferatoxin measured by assessing changes in the intensity of pain using the NPRS score, a widely used proprietary validated pain scale.
RTX is not approved for clinical use by regulatory authorities. Safety and efficacy have not been established.