As reported on BioSpace, Moderna has entered a commercialization agreement with Recordati valued at up to $160 million to support late‑stage development and future market introduction of mRNA‑3927, an investigational mRNA therapy for propionic acidemia (PA). Moderna will retain oversight of manufacturing and clinical development, while Recordati will manage commercialization. The deal includes a $50 million upfront payment and up to $110 million in milestone‑based payments.
Disease Background and Mechanism of Action
Propionic acidemia is a rare autosomal recessive metabolic disorder caused by deficient activity of the mitochondrial enzyme propionyl‑CoA carboxylase (PCC). Loss of PCC function results in accumulation of toxic organic acids, precipitating recurrent metabolic decompensation events that can lead to neurologic injury, cardiac complications, or death.
mRNA‑3927 delivers two mRNAs encoding the PCC α‑ and β‑subunits. The therapy is designed to restore functional PCC activity in hepatocytes, thereby reducing toxic metabolite buildup and stabilizing metabolic control.
Clinical Evidence to Date
Interim Phase I/II data published in Nature (2024) reported the following clinical observations:
- 70% reduction in the risk of metabolic decompensation during 12 months of treatment in eight participants.
- High incidence of treatment‑related adverse events (94%), most commonly transient lab abnormalities or infusion‑related events.
- Few treatment‑limiting toxicities, with Moderna reporting early signals of clinical benefit such as decreased hospitalization frequency and improved biomarker profiles.
While the small cohort limits the strength of conclusions, the early efficacy signal represents one of the most promising therapeutic approaches currently under investigation for PA.
A pivotal readout is expected later this year, which will be critical in determining the therapy’s long‑term risk‑benefit profile.
Strategic and Practice Implications
This partnership comes at a time when Moderna is restructuring due to declining COVID‑19 vaccine demand. For clinicians, the collaboration signals:
- Increased likelihood of commercial availability should pivotal data be positive.
- Potential expansion of treatment options for a population with significant unmet need and limited disease‑modifying therapies.
- A move toward mRNA‑based treatments in metabolic and genetic diseases, an area expected to grow rapidly over the next decade.
Recordati’s established presence in rare disease markets may help streamline future access pathways, including specialist distribution channels and reimbursement support.
