Novartis has done a little spring cleaning, sweeping a phase 2 osteoarthritis prospect and first-in-human radioconjugate out of its pipeline after assessing evidence on the programs.
The actions, which Novartis disclosed (PDF) in its first-quarter results, affect LRX712 and GIZ943. LRX712 was the more advanced of the two candidates. The Swiss drugmaker began a phase 2 trial of the asset in patients with knee osteoarthritis in 2020. A spokesperson for Novartis confirmed the removal of the drug candidate from the pipeline and the thinking behind the decision.
“Novartis discontinued the clinical development of LRX712, a chondrogenic drug, investigating its impact on osteoarthritis of the knee following an interim analysis of its phase 2 study which ultimately demonstrated a favorable safety profile, but an insufficient effect on knee cartilage,” the spokesperson said.
Researchers identified the synthetic small-molecule drug candidate via phenotypic screening. Preclinical tests suggested the molecule could drive cartilage repair without inducing abnormal bone formation. A drug with that profile could give patients an alternative to surgery, which can lead to fibrous or calcified cartilage that is unable to withstand the forces on the knee. LRX712 fell short of the hoped-for profile.
News of the LRX712 discontinuation arrived shortly after Novartis terminated a phase 2 trial of another osteoarthritis prospect, QUC398. The drugmaker was studying the ADAMTS-5 inhibitor in osteoarthritis knee pain but pulled the plug after an interim analysis found an “insufficient effect on pain relief.”
Novartis disclosed the scrapping of LRX712 alongside news that it has stopped development of GIZ943 in ovarian and lung cancers. GIZ943, also known as [177Lu] Lu-EVS459, is a radioligand therapy that targets cells that express folate receptor alpha (FRα). The spokesperson said Novartis stopped development “based on an assessment of potential benefit-risk from the phase 1 study.”
The trial got underway last year. Novartis recently stopped enrollment after recruiting four patients, well short of its target of 96. The study was supposed to determine the recommended dose in an escalation part and then evaluate its effects in an expansion stage.
FRα is overexpressed in many cancers, making it a potentially attractive target for radioligand therapies. Kidney toxicity is a long-standing concern, limiting the development of radioligand therapies against the target and helping antibody-drug conjugates become the modality of choice. AbbVie’s Elahere is already approved, and companies including Eisai and Genmab have FRα-directed ADCs in development.