Novartis Halts Phase 2 Trial of ADAMTS-5 Inhibitor for Osteoarthritis

Novartis has announced the termination of a phase 2 clinical trial evaluating QUC398, an investigational ADAMTS-5 inhibitor, for the treatment of osteoarthritis knee pain. The decision comes after an interim analysis revealed insufficient pain relief in patients, dealing a blow to the development of potential new therapies for this common joint condition.

Trial Termination and Drug Development Discontinuation

The randomized, placebo-controlled trial, which enrolled 101 patients, was discontinued following an interim analysis that showed an "insufficient effect on pain relief," according to a Novartis spokesperson. Despite the setback in efficacy, the drug candidate demonstrated a "good safety profile."

As a consequence of the trial's termination, Novartis has decided to discontinue further development of QUC398 for knee osteoarthritis. The company has stated that all trial participants will receive follow-up care as per the study protocol.

Background on ADAMTS-5 Inhibitors

ADAMTS-5 is an enzyme expressed in human cartilage and has been a target of interest in osteoarthritis research. Novartis's pursuit of an ADAMTS-5 inhibitor can be traced back to 2020 when the company acquired an anti-ADAMTS5 nanobody from Merck KGaA for 50 million euros upfront. At the time, the asset, known as M6495, was poised for phase 2 testing in osteoarthritis. It remains unclear whether M6495 is the same compound as QUC398.

This latest setback for ADAMTS-5 inhibitors follows a similar disappointment in the field. In 2020, Galapagos and Servier reported that their ADAMTS-5 inhibitor, GLPG1972 (also known as S201086), failed to demonstrate efficacy in a phase 2 study for knee osteoarthritis.

Implications for Osteoarthritis Treatment

The termination of Novartis's trial highlights the ongoing challenges in developing effective treatments for osteoarthritis. Currently, there are no anti-ADAMTS-5 treatments available on the market, and this recent failure may prompt researchers to reassess the potential of this therapeutic approach.

As the search for novel osteoarthritis treatments continues, the pharmaceutical industry faces the complex task of addressing the multifaceted nature of joint pain and cartilage degradation. The outcome of Novartis's trial underscores the need for innovative approaches and potentially new targets in the quest to improve the lives of millions suffering from this debilitating condition.