Moderna said Friday that one of its rare disease drug programs showed promise in its first clinical trials, according to an early look at the data.
The drug is meant to treat propionic acidemia, an uncommon genetic disorder that causes the body to not have enough of an enzyme essential for breaking down proteins. Estimates about how many people have this disorder vary, but those who do have difficulty processing certain foods and, early into life, will display symptoms like trouble eating, vomiting, dehydration and lethargy.
They may also experience diminished muscle tone and seizures, as well as life-threatening “metabolic decompensation events” and complications across multiple organ systems if not properly treated.
Moderna’s drug, like the rest of the company’s research pipeline, was created using messenger RNA technology. It’s designed to deliver the genetic instructions for that key missing enzyme so the liver can start making more of it.
The company initiated a Phase 1/2 trial in April 2021 to evaluate the safety of its drug and test a series of doses. A little more than six months later, Moderna also began an extension study to collect long-term safety data and allow participants from the earlier trial to continue getting the drug.
Moderna said Friday that, so far, 16 patients have been treated. The drug showed “encouraging early signs” that it is working in a dose-dependent manner and has potential clinical benefit. And, according to the company, most participants who reported metabolic decompensation events in the year leading up to the trial have had either fewer or none post-treatment.
Moderna said there have not been dose-limiting toxicities.
Nine participants experienced drug-related treatment-emergent adverse events, and eight experienced serious adverse events. Moderna said most of the serious events were related to the disease and not its drug. Six participants had mild infusion-related adverse events, though the majority of those happened during the first doses.
More details of these results were presented at an annual research conference focused on cell and gene therapies. In a note to clients, Jefferies analyst Michael Yee wrote that the presentation showed a 78% reduction of metabolic decompensation events among patients given higher doses of Moderna’s drug.
“This is a further improvement from the 50% reduction seen last year at lower doses,” the analyst wrote.
Yee estimates that propionic acidemia affects around 35,000 to 40,000 patients in the U.S. and could be a therapeutic market worth more than $1 billion.
“We continue to observe encouraging results with mRNA-3927 as we enter the dose-expansion phase,” Kyle Holen, Moderna’s head of development for therapeutics and oncology, said in a statement. “This is the first clinical trial reporting results of an mRNA therapeutic for intracellular protein replacement, and we currently have more than 13 patient-years of experience to date.”
Moderna said that 11 patients from the original trial are participating in the extension study. Together, the two investigations have administered more than 280 doses of the drug.
There currently aren’t any therapies that effectively address the underlying cause of propionic acidemia.