Novartis Halts Phase 2 Osteoarthritis Study of ADAMTS-5 Inhibitor Due to Lack of Pain Relief

Novartis discontinued a phase 2 clinical trial evaluating its investigational ADAMTS-5 inhibitor, QUC398, for osteoarthritis knee pain after an interim analysis found an "insufficient effect on pain relief." The decision was based on efficacy—not safety1 3.
The randomized, placebo-controlled trial enrolled 101 patients. All participants will continue to be monitored as specified in the study protocol1.
QUC398 showed a good safety profile, but due to lack of efficacy in pain relief, Novartis is discontinuing further development of the drug for knee osteoarthritis1 3.
Novartis had previously acquired an anti-ADAMTS-5 nanobody, M6495, from Merck KGaA in 2020 for €50 million upfront, which was also being developed for osteoarthritis. It is not confirmed if QUC398 is the same as M64951 10.
ADAMTS-5 is an enzyme responsible for degrading aggrecan in cartilage, making it a key target for disease-modifying osteoarthritis drugs (DMOADs)6 9.
Previous attempts to target ADAMTS-5 for osteoarthritis, including by other companies, have also failed to show clinical efficacy, with no ADAMTS-5 inhibitors currently approved or available on the market1 6 7.
The Novartis spokesperson did not indicate any plans to pursue QUC398 for other indications, and the molecule does not appear in Novartis’s current pipeline1.
Other ADAMTS-5 inhibitors, such as Galapagos/Servier’s GLPG1972, have also failed to demonstrate efficacy in phase 2 studies of knee osteoarthritis1 6.
Inhibition of ADAMTS-5 remains a promising but as-yet unproven therapeutic strategy for reducing cartilage degradation and potentially relieving joint pain or restoring joint function in osteoarthritis7 9.
There is currently a significant unmet need for effective, disease-modifying treatments for osteoarthritis7 9.