Lorecivivint may be the ‘first disease-modifying treatment’ for knee osteoarthritis
Click Here to Manage Email Alerts
WASHINGTON — Lorecivivint is superior to placebo for improving pain, function and structure at 12 months and beyond in patients with knee osteoarthritis, according to data presented at ACR Convergence 2024.
“Our previous studies of lorecivivint have shown benefit on pain, function and structure, with the longest study being 1 year,” Yusuf Yazici, MD, clinical associate professor of medicine at the New York University Grossman School of Medicine, told Healio. “We wanted to see the additional benefit of additional lorecivivint injections over multiple years. We were able to demonstrate pain, function and structural benefit also with multiple injections.”
Lorecivivint (Biosplice) is an intra-articular CLK/DYRK inhibitor that may modulate inflammatory and Wnt pathways, according to the researchers. To examine the agent’s long-term safety and efficacy, as well as its repeated use, in patients with moderate-to-severe knee OA, Yazici and colleagues conducted OA-07, a phase 3 extension trial.
The analysis included 276 patients with a mean age of 61 ± 8.2 years and a BMI of 31.8 ± 4.9 kg/m2. The cohort was 62.7% women, with 45.3% demonstrating a Kellgren-Lawrence Grade of 3 and a medial joint space width of 2.63 ± 0.69 m. Approximately two-thirds of the cohort were bilaterally symptomatic.
Results through the blinded portion of the trial at 1 year showed statistically significant improvements for lorecivivint compared with placebo. For example, the study drug bested placebo in WOMAC pain at week 24 (delta = –4.52; P = .044) and week 48 (delta = –5.19; P = .029), according to the researchers. Similarly, WOMAC function improved with lorecivivint compared with placebo at week 48 (delta = –4.86; P = .035). In addition, results through the crossover portion of the study to year 2 showed that all patients in the placebo group who switched to lorecivivint demonstrated improvements in both pain and function.
Meanwhile, compared with patients who received lorecivivint from the start, patients in the placebo arm demonstrated a numerical loss of joint space width 24 months after the first injection. By 36 months, this loss had reached statistical significance compared with the last available measurement of placebo before crossover, “assuming a) no change (delta = 0.22 mm, conservative scenario; P = .001) and b) progression (delta = 0.38 mm, realistic scenario; P < .001),” the researchers wrote.
“This is the first study to show benefit in pain, function and structure in knee OA patients in the same study, as far as we know,” Yazici said. “Patients with structurally advanced OA of the knee showed structural improvement with multiple injections over 3 years, in addition to pain and function improvement at 6 and 12 months.
“In addition, patients who were on placebo showed similar improvements once they crossed over to lorecivivint arm, further supporting the beneficial effects of lorecivivint,” he added.
Finally, regarding safety, the researchers reported no differences in major adverse events between treatment and placebo groups.
“Safety of lorecivivint was consistent with what we have seen so far in our development program, with no serious adverse events related to lorecivivint reported, and an overall adverse events profile no different than placebo,” Yazici said.
These findings may offer hope to patients and providers dealing with knee OA, according to Yazici.
“The results of the OA-07 study indicate that lorecivivint appears well-tolerated and may improve pain, function and structure in knee OA patients, potentially making it the first disease modifying treatment for knee OA,” he said.
Collapse
Yazici Y. Abstract #0792. Presented at: ACR Convergence 2024; Nov. 14-19, 2024; Washington, D.C.
Click Here to Manage Email Alerts