Novartis ends phase 2 osteoarthritis trial of ADAMTS-5 inhibitor

Novartis has announced the cessation of further development of its investigational drug QUC398, intended for the treatment of knee osteoarthritis. This decision follows the termination of a phase 2 clinical trial that was evaluating the efficacy of the ADAMTS-5 inhibitor for patients experiencing knee pain due to osteoarthritis. The decision was based on an interim analysis that revealed QUC398 did not provide sufficient pain relief, as communicated by a spokesperson from Novartis.

The clinical trial was a randomized, placebo-controlled study, enrolling 101 participants to assess the effectiveness of QUC398 when administered through intra-articular injection. Despite the study's discontinuation, Novartis confirmed that all participants would continue to receive follow-up care in accordance with the study protocol. The spokesperson further mentioned that QUC398 demonstrated a favorable safety profile throughout the trial.

Currently, Novartis has not provided any information regarding the potential evaluation of QUC398 for other medical conditions. Additionally, the investigational drug is not listed in Novartis’s online pipeline, leaving the future of this asset uncertain.

In 2020, Novartis acquired an anti-ADAMTS5 nanobody from Merck KGaA for an upfront payment of 50 million euros. At that time, the compound, referred to as M6495, was prepared for phase 2 trials aimed at addressing osteoarthritis. It remains unclear whether M6495 is synonymous with QUC398.

ADAMTS-5, an enzyme found in human cartilage, has been a target in the development of treatments for osteoarthritis due to its role in cartilage degradation. A previous collaboration between Galapagos and Servier sought to develop an ADAMTS-5 inhibitor known as GLPG1972, or S201086, for knee osteoarthritis. However, this asset also failed to show efficacy in phase 2 trials, with no observable signal of activity in the study's topline results.

As of now, there are no anti-ADAMTS-5 treatments available on the market for osteoarthritis, highlighting the challenges and complexities involved in targeting this enzyme for therapeutic purposes. The discontinuation of QUC398 development marks another setback in the quest for effective treatments targeting ADAMTS-5 for osteoarthritis.

Novartis’s decision to halt the development of QUC398 underscores the difficulties pharmaceutical companies face in developing new treatments for osteoarthritis, a condition that affects millions of people worldwide and for which effective, innovative treatments are still sought. Despite this setback, the quest for novel therapies targeting the underlying mechanisms of osteoarthritis continues, as researchers and pharmaceutical companies explore other potential avenues and compounds that might offer relief to those suffering from this chronic and debilitating joint condition.