Novartis Discontinues Development of Osteoarthritis and Cancer Therapies

Novartis, the Swiss pharmaceutical giant, has announced the discontinuation of two drug candidates from its pipeline following disappointing clinical results. The company has halted the development of LRX712, a potential treatment for knee osteoarthritis, and GIZ943, a radioligand therapy targeting ovarian and lung cancers.

LRX712: A Setback in Osteoarthritis Treatment

Novartis has terminated the clinical development of LRX712, a chondrogenic drug candidate that was being investigated for its impact on osteoarthritis of the knee. The decision came after an interim analysis of its phase 2 study revealed an insufficient effect on knee cartilage, despite demonstrating a favorable safety profile.

LRX712, a synthetic small molecule drug candidate identified through phenotypic screening, had shown promise in preclinical tests. It was initially believed to have the potential to drive cartilage repair without inducing abnormal bone formation, offering patients an alternative to surgery. However, the drug failed to meet the expected efficacy in human trials.

This discontinuation follows closely on the heels of another setback in Novartis's osteoarthritis program. The company recently terminated a phase 2 trial of QUC398, an ADAMTS-5 inhibitor being studied for osteoarthritis knee pain, due to insufficient pain relief observed in an interim analysis.

GIZ943: Radioligand Therapy Halted in Early Stages

In addition to LRX712, Novartis has also ceased the development of GIZ943, also known as [177Lu] Lu-EVS459, a radioligand therapy targeting folate receptor alpha (FRα)-expressing cells in ovarian and lung cancers. The decision was based on an assessment of the potential benefit-risk profile from the phase 1 study.

The trial for GIZ943 began last year but was stopped after enrolling only four patients, far short of its target of 96 participants. The study was designed to determine the recommended dose in an escalation part and then evaluate its effects in an expansion stage.

FRα has been a target of interest in cancer therapy due to its overexpression in many cancers. However, concerns about kidney toxicity have limited the development of radioligand therapies against this target. This has led to a shift towards antibody-drug conjugates (ADCs) as the preferred modality for targeting FRα, with AbbVie's Elahere already approved and other companies like Eisai and Genmab developing FRα-directed ADCs.

These pipeline adjustments reflect the ongoing challenges in drug development, particularly in complex areas such as osteoarthritis and targeted cancer therapies. As Novartis continues to refine its research and development strategy, the pharmaceutical industry watches closely for the next breakthrough in these critical therapeutic areas.