Gene Therapy
Elsewhere at OARSI 2024, updated data were reported on XT-150, a non-viral, plasmid-based gene therapy designed to express a proprietary variant (v) of IL-10.
Howard Rutman, MD, MBA, chief medical officer of Xalud Therapeutics, reported data from a patient subgroup analysis of a phase 2 trial, which evaluated the effects of single and repeat IA injections of XT-150.
Previously, it was found that a single dose of XT-150 (0.15 mg/mL or 0.45 mg/mL) given as a 1-mL IA injection did not meet its primary endpoint of a greater proportion of patients achieving a 30% or more improvement in WOMAC pain at 180 days vs a matching placebo.
Sara Freeman/Medscape Medical News
Dr. Howard Rutman
However, it was noted that 17% of the patients in the trial had a baseline WOMAC pain score of less than 8, so the new analysis focused on a modified intention-to-treat population of 210 patients who had baseline WOMAC pain scores of 9 or higher.
Two injections of XT-150 at a dose of 0.45 mg were found to produce the best effect on WOMAC pain, with a LSM change from baseline of −4.09 vs −2.74 for a single 0.45-mg injection (P = .044).
Dr. Rutman reported that the 0.45-mg dose would be the one moving forward into future studies as this had the best effect when they looked at various patient demographics, including baseline age, gender, body mass index, Kellgren-Lawrence grade, and use of concomitant medications.
XT-150 acts locally, does not integrate into the host genome, and “has a very favorable safety profile,” Dr. Rutman said. As it is not a protein, there is no antibody response, and this gives it the possibility for repeat dosing, with no drug-drug serious adverse events so far reported.
The Best Is Yet to Come?
“There’s a lot of things cooking that haven’t been presented here [at OARSI],” Dr. Lane observed.
“We are figuring out how to regenerate cartilage, and it’s a little different than throwing some stem cells in there. There’s some ground-breaking stuff [coming], it just takes us a while.”
Dr. Lane also noted that researchers were “really figuring out” how joints become painful, which will be a major step in figuring out how to make them less painful for patients.
“We’re making a lot of progress in ways that I don’t think we previously thought of, for example, the weight loss drugs. They probably have a central pain reduction effect, I think there’s a little overlap with the opioid receptors, so that’s pretty exciting. So, we’re getting there,” Dr. Lane said.
The congress was sponsored by the Osteoarthritis Research Society International.
Dr. Lane had no relevant conflicts to declare. The trial of PTP-001 (MOTYS) was funded by Bioventus. Ms. Pavesio is an employee of Doron Therapeutics, a subsidiary of Bioventus. The SPRINGBOARD trial with EP-104IAR was funded by Eupraxia Pharmaceuticals. Dr. Helliwell is an employee and stockholder of Eupraxia Pharmaceuticals. The trial of PPS was funded by Paradigm Biopharmaceuticals. Dr. Ahuja is an employee and stockholder of Paradigm Biopharmaceuticals and holds stock in ChitogenX. The trial of XT-150 was funded by Xalud Therapeutics. Dr. Rutman is an employee and equity holder of the company.
A version of this article appeared on Medscape.com.