Bis-choline tetrathiomolybdate

Investigational and not yet approved, but further along than most of the Wilson disease pipeline: its FDA application is actively being submitted rather than planned. In its Phase 3 trial it mobilized about 3 times more copper from tissues than standard of care (penicillamine, trientine and/or zinc), which may matter most for patients with neurologic Wilson disease where how quickly copper comes down affects the clinical trajectory. Its mechanism differs from both existing chelators and zinc.

Investigational copper-binding agent that locks copper into stable complexes with albumin, which the sponsor says blocks copper from being transported into the brain. Mechanistically distinct from trientine and penicillamine.

In the 48-week Phase 3 FoCus trial, ALXN1840 was generally well tolerated, and most reported side effects were mild to moderate. The most common side effect was a reversible rise in liver enzymes (transaminases), which signals the liver is irritated, and these rises were reversible^[1]. One finding matters especially for patients with neurologic Wilson disease: no worsening of neurological symptoms was seen when patients started ALXN1840^[1]. That is notable because older chelators, penicillamine in particular, can temporarily worsen tremor, speech, or movement problems when treatment begins.

ALXN1840 reached Phase 3 development under AstraZeneca/Alexion. In the pivotal Phase 3 trial it met its primary endpoint, mobilizing about 3 times more copper from tissues than standard of care, rapidly and sustained over 48 weeks, in both previously treated patients and those new to treatment. After AstraZeneca discontinued the program, Monopar Therapeutics licensed it and has reported new data and analyses from the Phase 2 WD-204 copper balance study^[3]. The FDA allowed Monopar to file on a rolling basis, meaning finished sections of the application go in for review while the rest is completed, and that submission started on July 22, 2026^[5].

Tetrathiomolybdate has been studied in Wilson disease for decades. Wilson Therapeutics developed bis-choline tetrathiomolybdate as WTX101 before Alexion acquired the company. AstraZeneca acquired Alexion in 2021 and discontinued the program in April 2023 after feedback from regulators, taking a $244 million write-down^[4]. Monopar Therapeutics licensed it from Alexion in October 2024^[2]. The FDA has granted ALXN1840 Fast Track and Orphan Drug designations, added Rare Pediatric Disease designation in June 2026, and Monopar began its rolling NDA submission in July 2026^[5].