A phase 1b study of a nonopioid, nerve-ablating painkiller from Sorrento Therapeutics showed rapid relief of osteoarthritic knee pain that lasted for nearly three months at its lowest dose, prompting the company to begin planning pivotal studies for this year.
Sorrento’s resiniferatoxin injection, or RTX, is 1000 times stronger than pure capsaicin—the compound that gives chili peppers their heat—with an eye-watering score of 16 billion on the Scoville scale. Jalapeño peppers, for example, only range between 3,500 and 8,000 Scoville units, while some of the world’s hottest peppers only break 3 million.
After being injected into the joint, RTX selectively binds to and burns out the nerve endings responsible for transmitting pain signals, while sparing other nerves. In the phase 1b dose-ranging study of about 30 treated patients, pain while walking was reduced by an average of 4.7 points on a 10-point scale compared to the control group after 84 days, with benefits seen as early as the day after the injection.
In addition, there were no dose-limiting toxicities or notable adverse events, the company said in a statement, with doses ranging from 5 to 30 micrograms. Patients will be monitored for one year after injection, according to the study, which is being expanded into phase 2.
“We believe this drug has the potential to rival the best-selling nonopioid pain drugs on the market, and make Sorrento an industry leader in nonopioid pain management,” said Sorrento Chairman and CEO Henry Ji. “We look forward to discussing our phase 1b data with the FDA and plan the final phase of our RTX knee osteoarthritis pain development program.”
RTX was brought up through Sorrento’s pain-focused subsidiary, Scintilla Pharmaceuticals, and is also being studied in treating intractable terminal cancer pain, as an epidural. In 2016, Scintilla had planned to spin out into its own, independent company, following the completed acquisitions of the pain biotechs Semnur Pharmaceuticals and Scilex Pharmaceuticals. However, in October 2017, the deal with Semnur fell through, according to Sorrento’s SEC filings.
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Several arthritis drugs have run into trouble in late-phase trials, including Anika Therapeutics’ Cingal and Regeneron’s anti-NGF antibody fasinumab.
Anika’s phase 3 miss in 2018 for its lead candidate, which combines cross-linked hyaluronic acid and the steroid triamcinolone hexacetonide, was unable to outperform the steroid alone after 26 weeks. However, the company does have a positive trial comparing Cingal to a placebo, and is angling for an FDA approval this year.
Regeneron, meanwhile, had to halt the higher-dose arms of a phase 3 study last year, following safety concerns. Fasinumab is being studied in osteoarthritis of the knee or hip, as well as chronic low back pain, across multiple phase 3 trials, the most advanced of which has already enrolled thousands of patients. Regeneron has been testing multiple regimens, but will now focus on the lower doses.