Moderna recently confirmed that its Phase I/II study examining candidate mRNA-3927 is progressing. It also shared that data showed a decrease in the number of metabolic decompensation events (MDEs) in trials of that therapeutic, and regulators seemed to be supportive of MDE as a primary endpoint for the study, according to the data and analytics firm.
In addition, the US biotech reported that all eligible participants in its study elected to continue to the Open Label Extension study.
mRNA-3927 targets a rare genetic disorder, propionic acidemia, in which patients are unable to process certain parts of proteins and lipids properly. Propionic acidemia is caused by the deficiency of propionyl-CoA carboxylase, which converts propionyl-CoA to methylmalonyl-CoA. Moderna's candidate is designed to alleviate the condition by activating propionyl-coenzyme A carboxylase.
If approved, the drug candidate is set to generate $278m in 2028, predicts GlobalData. The projections are based on the analyst consensus forecasting from GlobalData's Pharma Intelligence Center.
GlobalData anlalyst, Sarah Bundra, concludes: “Propionic acidemia is a rare but devastating genetic disorder. If Moderna’s mRNA-3927 proves to be successful, the therapy will provide a potential solution for a patient population facing a scarcity of options.”
A paper in Nature, published in November 2022, maintains that a series of challenges remains to be addressed before mRNA can be established as a general therapeutic modality with broad relevance to both rare and common diseases.
"An array of new technologies is being developed to surmount these challenges, including approaches to optimize mRNA cargos, lipid carriers with inherent tissue tropism and in vivo percutaneous delivery systems. The judicious integration of these advances may unlock the promise of biologically targeted mRNA therapeutics, beyond vaccines and other immunostimulatory agents, for the treatment of diverse clinical indications."
In many cases, said the authors, it will be necessary for mRNA therapeutics to engage a particular target pathway, cell, tissue or organ. This requirement places greater importance on the efficiency of uptake at the target cell, which drives the duration and level of expression.
"The tissue bioavailability, circulatory half-life and efficiency of the lipid-based carrier to deliver to the tissue of interest can be strictly rate limiting. Aside from the liver, which is readily targeted by intravenous delivery, efficient delivery to solid organs remains challenging. Another major hurdle is repeated dosing, which is often required in the treatment of chronic diseases. Even with optimized mRNA chemical modifications and advanced LNPs, chronic dosing eventually activates innate immunity, with concomitant attenuation of therapeutic protein expression. Despite these remaining challenges, a host of emerging technologies is under development to systematically address them."
Leading non-vaccine mRNA therapeutics
mRNA-3927 is one of five non-vaccine mRNA therapeutics currently in clinical trial development, outlined GlobalData. The other four non-vaccine mRNA therapeutics are: BNT-141 by BioNTech, which is targeting ovarian cancer, bile duct cancer, adenocarcinoma of the gastroesophageal junction, colorectal cancer, pancreatic cancer, gastric cancer, and solid tumors; LUNARGSD3/UX053 by Ultragenyx, which is targeting glycogen storage disorder type III, also known as Cori’s Disease; mRNA-3705, Moderna’s second candidate, for methylmalonic acidemia; and OTX-2002 by Omega Therapeutics for hepatocellular carcinoma and solid tumors.
In November last year, the US Food and Drug Administration (FDA) granted Orphan Drug Designation for OTX-2002 for the treatment of hepatocellular carcinoma. If approved, OTX-2002 is projected to have the highest revenue by 2028, with sales of $1.6bn during that year, said the data analytics provider. As per GlobalData’s analyst consensus forecast, the sales of all five therapeutics are forecast to reach over $2bn by 2028.
mRNA is a single-stranded ribonucleic acid that is transcribed from a strand of DNA. It carries the coding information for protein synthesis. mRNA therapeutics involve the delivery of in vitro transcription of mRNA into a target cell, where cellular machinery is then able to translate the mRNA into a functional protein. The idea is that these proteins can help the immune system prevent or treat certain diseases.
