Moderna reports 'positive' Phase 1 results from study of mRNA-1944
Moderna announced positive data in the first analysis of safety and activity in its Phase 1 study evaluating escalating doses of mRNA-1944 administered via intravenous infusion in healthy adults. mRNA-1944 encodes for an antibody with activity against chikungunya virus. At all three dose levels, the administration of mRNA-1944 led to detectable levels of CHKV-24 antibody in all participants, ranging from 1 microg/mL to 14 microg/mL. These results mark the first systemic mRNA therapeutic to show production of a secreted protein in humans. mRNA-1944 is being developed with financial support from the Defense Advanced Research Projects Agency, an agency of the U.S. Department of Defense. mRNA-1944 is the first development candidate from the company's systemic therapeutics modality to start clinical testing and utilizes the same lipid nanoparticle formulation as the company's rare disease program for methylmalonic acidemia. A total of 22 healthy adults have been enrolled in the study to date. The initial analysis evaluated the safety and pharmacology of intravenous administration of mRNA-1944 at three dose levels of 0.1 mg/kg, 0.3 mg/kg, and 0.6 mg/kg; six participants received placebo. Administration of mRNA-1944 resulted in dose-related increases in CHKV-24 antibody levels, with average Cmax antibody levels of 2.0, 7.9 and 10.2 ug/mL at the low, middle and high doses, respectively. At all doses, all participants exceeded the levels of antibody expected to be protective against chikungunya infection following a single dose, with the middle and high doses projected to maintain antibody levels above protective levels for at least 16 weeks. All participants also showed circulating neutralizing antibody activity against chikungunya virus replication in an NT50 assay, demonstrating that mRNA-1944 resulted in the production of fully functional protein in vivo. All participants in the study received antihistamine premedication. No participants received corticosteroids either as premedication or treatment. None of the participants treated with mRNA-1944 at the low or middle doses experienced significant adverse events. Three of the four participants at the high dose had infusion-related AEs, with the highest grade by subject being Grade 1, Grade 2 and Grade 3. The Grade 3 AEs were tachycardia and an elevated white blood cell count. The same participant experienced Grade 2 AEs of nausea, emesis, fever and inverted T waves on a routine EKG (without associated cardiac symptoms and which later resolved). The fourth participant at the high dose had no related adverse events. There were no meaningful changes in liver or kidney laboratory results. There have been no serious AEs in the study. All AEs were transient and resolved spontaneously without treatment.