Massachusetts-based biotech Moderna has shared results from its early clinical test for the treatment of the rare inherited metabolic disorder propionic acidemia (PA), according to which cellular machinery in the body can be modified to produce therapeutic molecules that can reduce the relative risk of life-threatening events occurring in patients by over 65%.
Moderna first became a household name due to its genes, but the biotech has been looking to move towards therapeutics for a while now. The goal for the firm is to turn human cells into drug production factories that can produce therapeutic molecules to treat diseases in new and innovative ways by delivering proteins to their intracellular targets.
This is the first time any biotech has reported clinical data on intracellular protein replacement through mRNA therapeutics.
It is due to the deficiency of an enzyme produced by the two subunit proteins, PCCA and PCCB, that patients suffer from PA. In the study, children suffering from the disease were given multiple doses of Moderna’s nanoparticle-encapsulated dual mRNA therapy called mRNA-3927, which encodes both the subunit constituents of the deficient enzyme so that the root cause of the disease can be dealt with by triggering production.
This would also prevent the buildup of harmful compounds that cause the disease symptoms to occur.
In the clinical data drop for the trial, across five dose cohorts, only 3 drug-related serious adverse events (SAEs) were reported, with the most severe instance being when one patient developed grade 3 pancreatitis. Seizures and diminished muscle tone are other possible SAEs that may occur. However, there were no reports of dose-limiting toxicities.
Before some of the patients started this therapy, they suffered from life-threatening metabolic decompensation events, which have decreased since starting the treatment. In four groups of patients that received treatment every two weeks, an over 75% overall relative risk reduction was observed, which is a sign of early efficacy. Across the trial, a 66% overall relative risk reduction was observed.
The firm has successfully administered approximately 300 doses of mRNA-3927, and 5 patients have been taking the therapy for over a year now. The trial began in April 2021, and now an extension study to collect long-term safety data is set to begin. This would also allow patients currently receiving treatment to continue doing so.
“We continue to observe encouraging results with mRNA-3927 as we enter the dose-expansion phase, where we will further assess safety and efficacy and determine the recommended dose for future clinical studies. We currently have more than 13 patient-years of experience to date,” Kyle Holen, M.D., head of development, therapeutics, and oncology at Moderna, shared.
While estimates for the exact number of people suffering from PA vary, symptoms like trouble eating, vomiting, dehydration, and lethargy are common across the board, and patients suffering from the disorder will have trouble processing certain foods from early on in life.
According to Jefferies analyst Michael Yee, up to 40,000 patients in the U.S. alone suffer from PA, making it a therapeutic market worth more than $1 billion.