Moderna Releases Promising Data from Phase I/II Clinical Trial on mRNA-3927 for Propionic Acidemia

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Moderna has announced promising data from its Phase I/II study for mRNA-3927, an investigational mRNA therapy for the potential treatment of propionic acidemia (PA). Currently in progress, the open-label, dose optimization and extension trial is evaluating the safety and efficiency of the medication. So far, the trial has included 16 participants, with over 340 doses of the treatment administered. Additionally, no significant adverse events (AEs) have been reported that were related to mRNA-3927. The study’s biggest finding was that the relative risk for metabolic decompensation events (MDEs) were reduced by 70%.¹

"We are excited to share the first published clinical data utilizing an mRNA therapy for intracellular protein replacement," said Kyle Holen, MD, SVP, head of development, therapeutics and oncology, Moderna, in a press release. "PA is a rare, inherited metabolic disorder that results from the body's inability to process certain parts of proteins and lipids due to a specific enzyme deficiency. For people with PA, harmful amounts of toxic metabolites can build up in the body and lead to metabolic decompensation events (MDEs) and multisystemic complications. These interim data indicate early signs of potential clinical benefit with mRNA-3927, and importantly also demonstrate that mRNA-3927 has infrequent treatment-limiting side effects. I'm particularly proud of these results given that there are currently no therapeutic treatments approved for patients with this disease."

According to Medline Plus, PA affects one in every 100,000 people in the United States. However, it appears to be more common in populations such as the Inuit of Greenland, Amish people, and those of Arabian origin.²

“Propionic acidemia is an inherited disorder in which the body is unable to process certain parts of proteins and lipids (fats) properly,” reports Medline Plus. “It is classified as an organic acid disorder, which is a condition that leads to an abnormal buildup of particular acids known as organic acids. Abnormal levels of organic acids in the blood (organic acidemia), urine (organic aciduria), and tissues can be toxic and can cause serious health problems.”

The National Organization for Rare Disorders (NORD) classifies PA as a deficiency of propionyl-CoA carboxylase. Symptoms generally begin at the start of life, and include:

• Hypotonia
• Vomiting
• Lethargy
• Dehydration
• Seizures^2,3

“Less commonly, the signs and symptoms of propionic acidemia appear during childhood and may come and go over time,” according to Medline Plus. “Some affected children experience intellectual disability or delayed development. In children with this later-onset form of the condition, episodes of more serious health problems can be triggered by prolonged periods without food (fasting), fever, or infections.”

References

1. Phase 1/2 Interim Data on Moderna’s mRNA-3927, an Investigational mRNA Therapy for Propionic Acidemia, Published in Nature. Moderna. April 3, 2024. Accessed April 4, 2024. https://investors.modernatx.com/news/news-details/2024/Phase-12-Interim-Data-on-Modernas-mRNA-3927-an-Investigational-mRNA-Therapy-for-Propionic-Acidemia-Published-in-Nature/default.aspx

2. Propionic acidemia. Medline Plus. Accessed April 4, 2024. https://medlineplus.gov/genetics/condition/propionic-acidemia/

3. Propionic Acidemia. NORD. April 17, 2020. Accessed April 4, 2024. https://rarediseases.org/rare-diseases/propionic-acidemia/