Key clinical point: Promising results are reported for intra-articular Wnt inhibitor SMO4690, which might eventually become the first disease-modifying OA drug.
Major finding: The 0.23-mg dose of SMO4690 proved superior to placebo for four key patient-reported outcomes.
Study details: This was a 24-week, randomized, multicenter, placebo-controlled, double-blind, phase 2b study in 695 patients with moderately to severely symptomatic knee OA.
Disclosures: The presenter is chief medical officer at Samumed, the study sponsor.
Source: Yazici Y et al. Arthritis Rheumatol. 2018;70(Suppl 10), Abstract L03.
CHICAGO – A single intra-articular injection of a novel drug known for now as SMO4690 resulted in statistically significant and clinically meaningful improvements in pain and physical function through 6 months of follow-up in a phase 2b study including 695 patients with moderately to severely symptomatic knee OA, Yusuf Yazici, MD, reported at the annual meeting of the American College of Rheumatology.
Bruce Jancin/MDedge News
Dr. Yusuf Yazici
Based on the encouraging results of this and another large phase 2 study, two pivotal phase 3, randomized clinical trials are due to start in the spring of 2019. If the results are positive, SMO4690 could become the first approved disease-modifying OA drug (DMOAD), something that’s been a long-sought, high-priority goal in rheumatology, noted Dr. Yazici, chief medical officer at San Diego–based Samumed, which is developing the drug, and a rheumatologist at New York University.
SMO4690 is a small molecule inhibitor of the Wnt signaling pathway. The drug has two distinct mechanisms of action for treatment of knee OA: It has an anti-inflammatory effect and it protects cartilage from degeneration, as demonstrated by a clinically significant improvement in joint space width by x-ray, compared with placebo at 12 months of follow-up after a single baseline injection in the earlier 455-patient, phase 2 study. Also, animal studies suggest SMO4690 generates cartilage, an exciting possibility now being evaluated in two ongoing serial MRI studies in knee OA patients.
Dr. Yazici presented patient-reported outcomes from the 695-patient, 24-week, multicenter, randomized, placebo-controlled, double-blind, phase 2b study, which evaluated four different concentrations of SMO4690. The 0.07- and 0.23-mg per 2-mL injection doses proved significantly better than placebo at 12 weeks – the primary endpoint – for all patient-reported outcomes.
The 0.23-mg dose of SMO4690 remained superior to placebo for all four patient-reported outcomes at subsequent assessments at weeks 16, 20, and 24. The 0.07-mg dose remained significantly better than placebo through week 20.
As in the earlier phase 2 study, SMO4690 raised no significant safety concerns. Adverse events were similar in type and frequency in the active-treatment and placebo groups.
The study was sponsored by Samumed, where Dr. Yazici is employed as chief medical officer.