Novo Nordisk/Prothena’s coramitug TTR antibody gains FDA Fast Track status

Prothena Corporation plc (Nasdaq: PRTA), headquartered in Dublin, announced that Novo Nordisk has received US FDA Fast Track Designation for coramitug (PRX004), a humanized monoclonal antibody targeting misfolded transthyretin (TTR), for the treatment of transthyretin amyloidosis with cardiomyopathy (ATTR-CM). Novo Nordisk acquired full worldwide rights to the ATTR amyloidosis pipeline from Prothena in July 2021; under that agreement, Prothena is eligible to receive up to USD 1.2 billion in upfront and milestone payments, with USD 150 million earned to date.

Fast Track Designation enables rolling review of the biologics license application and more frequent FDA interactions during development. Coramitug has not previously been reported to hold other US expedited designations beyond the current Fast Track status, though the announcement notes prior Orphan Drug Designation.

Coramitug’s proposed mechanism distinguishes it from the two approved therapeutic classes in ATTR-CM. TTR stabilizers such as tafamidis and acoramidis reduce the rate of amyloid deposition by preventing tetramer dissociation, while RNA-silencing agents reduce hepatic TTR production. Coramitug instead targets misfolded, non-native TTR to promote clearance of existing amyloid deposits through antibody-mediated phagocytosis, without binding the normal tetrameric form of the protein. The company describes this as a depleter mechanism that could function as monotherapy or in combination with stabilizer or silencer approaches.

The clinical basis for the designation draws on a Phase 2 randomized, double-blind, placebo-controlled trial (NCT05442047) in 104 participants with ATTR-CM, published in Circulation and presented as a late-breaking session at the American Heart Association Scientific Sessions on November 10, 2025. In the 60 mg/kg intravenous cohort, coramitug produced a 48% placebo-adjusted reduction in NT-proBNP at Week 52, a result the authors characterized as statistically significant. NT-proBNP is an established prognostic biomarker in heart failure and ATTR-CM. The 60 mg/kg dose was also associated with improvements in echocardiographic parameters of cardiac function. Results on the six-minute walk test, a co-primary endpoint, were mixed and did not reach statistical significance. More than 80% of enrolled participants were already receiving standard-of-care therapy at baseline, making the NT-proBNP reduction notable as an incremental signal on top of existing treatment. Full p-values and confidence intervals from the Circulation publication were not reproduced in the Fast Track announcement.

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Novo Nordisk is now evaluating coramitug in the Phase 3 CLEOPATTRA trial (NCT07207811), enrolling approximately 1,280 participants with ATTR-CM, with primary completion expected in 2029. A separate Phase 1 open-label imaging study (NCT07448623) is assessing the biodistribution of zirconium-89-labeled coramitug via PET/CT to evaluate whether the antibody localizes to myocardial tissue and engages TTR amyloid deposits in the heart.

Research context

ATTR-CM results from progressive deposition of misfolded TTR as amyloid fibrils in the myocardium, leading to restrictive cardiomyopathy and heart failure. Approved therapies slow progression but do not clear existing deposits, leaving a gap for agents that could reverse or reduce the amyloid burden already present at diagnosis. The CLEOPATTRA trial is powered around cardiovascular mortality and morbidity endpoints, positioning coramitug for a potential label claim that goes beyond stabilization. Competing amyloid-directed programs are in earlier stages, and no amyloid-clearing agent has yet reached approval in ATTR-CM, making the Phase 3 readout, expected after 2029, a closely watched event in the cardiovascular amyloidosis field.


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