MMA-101 STABILITY STUDIES EXTENSION & ADDITIONAL ANALYTICAL TESTING TO SUPPORT DEVICE COMPATIBILITY

Investigators

Abstract

The National Center for Advancing Translational Sciences (NCATS) is collaborating with the National Human Genome Institute (NHGRI) to advance an adeno-associated virus gene therapy candidate as possible treatment for isolated methyl malonic acidemia (MMA). Background: MMA is a serious, life-threatening inherited metabolic disorder that is caused most frequently by biallelic pathogenic variants in the gene coding for the mitochondrial enzyme methylmalonyl-CoA mutase (MMUT). Patients who harbor variants in MMUT resulting in very low or absent MMUT enzymatic activity are the most severely affected (mut0 subtype), while those with partial deficiency (mut – ) are associated with markedly milder phenotypes and improved survival. For mut0 patients, mortality remains high and is estimated at 40-47% in different case series, despite newborn screening and advanced care. Gene therapy with MMA-101 (AAV8-MMUT) to replace the MMUT gene would be desirable because it avoids the surgical and lifelong immunosuppression risks associated with liver transplant. An open-label, single-center, first-in-human trial will evaluate the AAV8-MMUTgene therapy. Two cGMP/clinical lots of MMA-101 (AAV8-MMUT), G-NORMA-030 and G-NORMA-057, and two cGMP/clinical lots of diluent/formulation buffer (FFB-G-004 and FFB-G-023) have been manufactured by Viralgen. The products met all the release acceptance criteria for clinical use. Viralgen performed stability testing up to 36M on the cGMP lots. Rare Diseases