Bis-choline tetrathiomolybdate

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].

Those results were published in Hepatology Communications on May 19, 2026. Of 9 patients kept on a copper-controlled diet, 8 were analyzed. On average their copper balance fell below their own pre-treatment level, with the drop statistically significant from day 4 and totaling about 6mg over the 21 days measured, mostly because more copper left the body in stool^[8].

Monopar points to a Journal of Hepatology letter arguing that a Wilson disease drug's effect on copper balance should be judged against each patient's pre-treatment level^[9]. AstraZeneca's view in 2023 was that its Phase 2 studies had not shown copper actually being removed from the body^[5]. The study was funded by Alexion and AstraZeneca Rare Disease, and some of the paper's authors work for Monopar^[8].

In a separate Phase 2 study, WD-205, 29 patients who had already been treated for a median of 13.8 years took ALXN1840 alone for 48 weeks with no comparison group. Monopar reported at the EASL Congress in June 2026 that among the 24 patients with liver biopsies at the start and at week 48, between 67% and 96% were stable or better depending on the liver measure, that copper in the liver did not change significantly, and that a Wilson disease neurologic rating scale (UWDRS Part III) and quality of life improved from the start^[10].

New FoCus analyses Monopar presented in June 2026 looked at patients who had neurologic symptoms at the start: their UWDRS Part III scores improved significantly over time on ALXN1840 but not on standard care, and overall clinical improvement at week 48 was greater with ALXN1840^[11]. 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^[6].

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 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. Across its Phase 2 and Phase 3 studies, Monopar reports 266 patients treated for a median of 2.58 years, with serious side effects judged to be caused by the drug in 4.9%, serious neurologic events in under 1% and no treatment-related deaths^[11].

In the WD-204 study, rises in the liver enzyme ALT were mild and went away when the dose was adjusted^[8]. In November 2026 Monopar reported a neutral molybdenum balance, meaning molybdenum did not build up in the body, no molybdenum toxicity, and uric acid staying within normal limits over 6 years of treatment^[12].

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 2 Phase 2 mechanistic studies missed their main goals and after discussions with regulators, taking a $244 million write-down^[4][5].

AstraZeneca's chief executive said those studies had not shown that copper was actually removed from the body. 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^[6].