Moderna, a venture pioneering RNA (mRNA) therapeutics and vaccines to create a new generation of transformative medicines for patients, announced the Food and Drug Administration (FDA) has completed their review of the Investigational New Drug (IND) application for mRNA-3927—its investigational mRNA therapeutic for propionic acidemia (PA)—and allowed it to proceed to clinical trials. They will now move the investigational product to Phase I/2 clinical trials in patients with propionic acidemia.
Orphan Drug & Rare Pediatric Disease Designations
mRNA-3917received Orphan Drug and Rare Pediatric Disease designations from the FDA and Orphan Designation by the European Medicines Agency (EMA).
What is mRNA-3917?
Developed from their “Software of Life” operating system, mRNA-3927 is designed to instruct the body to restore the missing dysfunctional proteins that cause PA. mRNA contains two mRNAs that encode for the alpha and beta subunits of PCC, encapsulated within Moderna’s proprietary lipid nanoparticle (LNP). mRNA-3927 is intended for patients with PA regardless of whether they have defects in the alpha or beta subunit. It uses the same proprietary lipid nanoparticle (LNP) formulation used in the company’s antibody against chikungunya virus (mRNA-1944) and MMA (mRNA-3704).
Upcoming Clinical Trials
Moderna will initiate an open-label, multi-center, dose escalation Phase I/2 study of multiple ascending doses of mRNA-3927 in primarily pediatric patients with PA in the U.S. and Europe. The objective of the study will be to evaluate the safety and tolerability of mRNA-3927 administered via IV infusion, characterize the pharmacokinetic profile of mRNA-3927 and assess the pharmacodynamic response as assessed by changes in plasma biomarkers.
This is the second rare disease candidate from Moderna’s pipeline with an open IND. The first program, mRNA-3704 is designed to treat methylmalonic acidemia (MMA)—another rare metabolic disorder. The company is currently recruiting patients with MMA for a Phase 1/2 study of mRNA-3704.
Rare Disease Focus
Moderna was profiled in TrialSite News as “developing the software of life.”
Propionic acidemia (PA) is a rare metabolic disorder characterized by deficiency of propionyl CoA carboxylase, an enzyme involved in the breakdown (catabolism) of the chemical “building blocks” (amino acids) of certain proteins. Symptoms most commonly become apparent during the first weeks of life and may include abnormally diminished muscle tone (hypotonia), poor feeding, vomiting, listlessness, (lethargy), excessive loss of fluids from bodily tissues (dehydration), and episodes of uncontrolled electrical activity in the brain (seizures). As reported in Rarediseases.org, without appropriate treatment, coma and potentially life-threatening complications my result. In rare cases, the condition may become apparently later during infancy and thus be associated with less severe symptoms and findings. It is inherited as an autosomal recessive trait.
According to the NIH, PA affects about 1 in 100,000 people in the United States. The condition appears to be more common in several populations, including the Inuit population of Greenland, some Amish communities, and Saudi Arabians.
PA and MMA Share Disease Pathology
PA and MMA share similar disease pathology and are both typically treated by metabolic specialists. In order to characterize and describe the natural history of these disorders and identify potential clinical and biomarker endpoints, Moderna is conducting a global, multi-center, non-interventional observational study for patients with confirmed diagnoses of PA or MMA.
Existing Clinical Trial for MMA
TrialSite News interprets the Moderna press release that they will incorporate a global multi-center, non-interventional study for patients with confirmed diagnoses of PA or MMA hence combining into one study. The existing study posted on Clinicaltrials.gov started recently in May 2019 and estimated study completion date is November 2024.
Moderna Sites for the Phase I methylmalonic acidemia study:
- UCLA Health
- Stanford University
- University of Florida College of Medicine
- Emory University, Children’s Hospital of Atlanta
- Johns Hopkins University Hospital
- Boston Children’s Hospital
- Mount Sinai Medical Center
- Duke University Medical Center
- Children’s Hospital of Philadelphia
- Children’s Hospital of Pittsburgh (UPMC)
- Vanderbilt University Medical Center
- University of Utah Hospital & Clinics
- Seattle Children’s Hospital
Tal Zaks, MD,PhD, chief medical officer at Moderna reports of the excitement for that they are excited for their “second open IND for a rare disease program and are preparing to move mRNA-3927 into a Phase 1/2 clinical trial in patients with propionic acidemia.” He reminds the reader that “there are no approved therapies to treat the underlying cause of propionic acidemia, a rare metabolic disorder that can lead to a toxic buildup of acids in the body. We believe mRNA-3927 has the potential to restore the missing or dysfunctional proteins and thus relieve the acidemia that causes this disease in children.”
Call to Action: If you or a loved one has a diagnosis of propionic acidemia or methylmalonic acidemia, then it makes sense to monitor these early state Moderna clinical trials. Sign up for the TrialSite News newsletter as we will track as well. Interested in connecting with one of the clinical sites involved with the study—we can help you connect.