Monopar Therapeutics Inc. (Nasdaq: MNPR), an Illinois-based biopharmaceutical company, has initiated a rolling submission of a New Drug Application to the US FDA for ALXN1840 (tiomolibdate choline, TMC), an investigational copper-sequestering agent for Wilson disease. The FDA has authorized Monopar to submit completed sections of the application while the remaining sections are finalized, and the company said it has already filed the first completed portions. If accepted for filing and subsequently approved, ALXN1840 would represent the first therapy with a novel mechanism of action cleared in the US for Wilson disease in decades.
Wilson disease is a rare genetic disorder, affecting roughly one in 30,000 people, caused by mutations in the ATP7B gene that impair the body's ability to excrete copper, leading to toxic accumulation in the liver, brain and other organs. Existing therapies—penicillamine, trientine (marketed as Syprine and, since 2022, as Cuvrior), and zinc acetate (Galzin)—work by binding copper for urinary excretion or blocking intestinal absorption, but carry documented limitations, including nephrotoxicity, autoimmune reactions and, notably, the potential for paradoxical neurological worsening upon initiation.
ALXN1840 operates through a distinct pathway. It is described as a first-in-class albumin tripartite complex activator, mobilizing excess copper into stable complexes with serum albumin that suppress copper's redox reactivity, limit oxidative damage and block its transport across the blood-brain barrier. Clinical data cited by Monopar indicate the drug increases fecal, rather than urinary, copper excretion—a mechanistic distinction from the approved chelator class.
The submission is supported by a Phase III pivotal trial in which ALXN1840 met its primary endpoint of copper mobilization, demonstrating a significantly greater effect than standard of care over 48 weeks in both previously treated and treatment-naïve patients. Across the broader ALXN1840 development program, Monopar has reported 645 patient-years of follow-up among 266 patients, with what it characterizes as durable clinical improvement and a well-characterized safety profile. Neurologic outcome data from the trial, presented earlier this year at the American Academy of Neurology and European Academy of Neurology meetings, showed higher rates of neurologic improvement and lower rates of worsening with ALXN1840 relative to standard of care, addressing a population in which current chelators can be poorly tolerated.