Novartis Terminates Phase 2 Trial of ADAMTS-5 Inhibitor QUC398 for Knee Osteoarthritis Due to Insufficient Pain Relief

Apr 17, 2025 09:19 CST Updated 09:19

Novartis

Drug Development and Manufacturing

Novartis has terminated the development of its ADAMTS-5 inhibitor QUC398 for the treatment of knee osteoarthritis (OA). An updated entry on the ClinicalTrials.gov website this week showed that a Phase II proof-of-concept study of the therapy was terminated due to "sponsor decision."

According to a spokesperson for Novartis, the interim analysis showed "Good safety profile, but insufficient pain relief effect", the study was stopped in December of last year. Therefore, Novartis stated that it will not advance the research of QUC398 in knee osteoarthritis."

The trial was initiated in November 2022 to evaluate the effects of intra-articular injection of QUC398 on pain and cartilage preservation in patients with symptomatic knee osteoarthritis (OA). The primary outcome measure is the change from baseline in the Knee Injury and Osteoarthritis Outcome Score (KOOS) pain subscale at week 12.

In 2020, Novartis acquired the anti-ADAMTS5 nanobody from Merck with a prepayment of 50 million euros. At that time, the drug, named M6495, was ready for Phase II clinical trials for osteoarthritis. It is currently unclear whether M6495 is QUC398.

The failure of QUC398 is another precedent of setbacks in the field of ADAMTS-5 inhibitors. In 2020, Galapagos and Servier reported that their candidate drug GLPG1972 (S201086) "did not show an activity signal" in the Phase II ROCCELLA trial. The study found no statistically significant difference between GLPG1972 and placebo in cartilage thickness or clinical outcomes after 52 weeks of treatment.

ADAMTS-5 is an enzyme expressed in human cartilage, and currently, no anti-ADAMTS-5 treatments have been approved.