Moderna Doses First Patient in Study of mRNA Therapeutic for MMA

Moderna recently announced that the first patient has received a dose in a Phase 1/2 study of its mRNA therapeutic, mRNA-3705, for methylmalonic acidemia (MMA). 

The open-label landmark study will evaluate the safety and tolerability of up to five different dosing regimens of mRNA-3705. Researchers will administer the therapeutic via intravenous infusion in patients with isolated MMA due to a deficiency in the mitochondrial enzyme methylmalonic-CoA mutase (MUT).

“We would like to thank Dr. Santra and the whole team in Birmingham for their efforts and collaboration to achieve this milestone moment of dosing the first MMA patient with our mRNA therapeutic,” Ruchira Glaser, MD, senior vice president and therapeutic area head of rare disease, autoimmune & cardiovascular at Moderna, said in the announcement.

“This is another step forward in Moderna’s mission to deliver on the promise of mRNA science to create a new generation of transformative medicines for patients,” Glaser continued. 

Methylmalonic acidemia is a rare, life-threatening metabolic disorder that is most commonly caused by MUT deficiency. 

The deficiency can lead to metabolic crises due to toxic buildup of acids in the body and progress into multi-organ disease. Standard care includes dietary and palliative measures, a Moderna spokesperson said. But there are currently no approved therapies for the disorder. 

mRNA-3705 was designed to restore the missing or dysfunctional proteins that cause MMA and consists of mRNA encoding human MUT, encapsulated with Moderna’s lipid nanoparticle (LNP).

FDA previously granted Orphan Drug and Rare Pediatric Disease designation to mRNA-3705. And Moderna owns global commercial rights to the therapeutic.  

Experts also believe that gene therapy is a promising potential treatment for MMA. 

Researchers performed the first successful in vivo gene therapy experiments using an early generation adenovirus type 5. These studies showed that an adenovirus, customized to express the MUT cDNA under the control of the cytomegalovirus promoter, could rescue the lethal neonatal phenotype of the MMA knockout mice. 

Specifically, over 50 percent of the Ad5-treated MUT mice survived for 15 days, with one mouse surviving for 8 months.

Overall, the Ad gene delivery experiments provided proof of the in vivo potential for viral gene delivery as a treatment for MMA.

“We are delighted to have been able to treat the first patient in the world with this new medicine here in Birmingham,” Saikat Santra, MD, pediatric inherited metabolic medicine consultant of clinical inherited metabolic disorders at Birmingham Women’s and Children’s NHS Foundation Trust, said in the recent announcement. 

“We sincerely hope that it brings this brave patient, and many more like them, a brighter future free of the restrictions of this terrible disease,” Santra continued.