Rare Daily Staff
Eiger BioPharmaceuticals said that it has initiated submission of a New Drug Application for Lonafarnib for the treatment of the ultra-rare and fatal disease progeria and progeroid laminopathies that cause premature aging in children.
Progeria, also known as Hutchinson‐Gilford Progeria Syndrome (HGPS) is caused by a point mutation in the LMNA gene, which encodes the lamin A protein, yielding the farnesylated aberrant protein, progerin. Lamin A protein is part of the structural scaffolding that holds the nucleus together. Children with Progeria die of the same heart disease that affects millions of normally aging adults (arteriosclerosis), but at an average age of 14.5 years. Disease manifestations include severe failure to thrive, scleroderma‐like skin, global lipodystrophy, alopecia, joint contractures, skeletal dysplasia, global accelerated atherosclerosis with cardiovascular decline, and debilitating strokes. It is estimated that 400 children worldwide have progeria.
Progeroid laminopathies are genetic conditions of accelerated aging caused by a constellation of mutations in the lamin A and/or Zmpste24 genes yielding farnesylated proteins that are distinct from progerin. While non‐progerin producing, these genetic mutations result in disease manifestations with phenotypes that have overlap with, but are distinct from, progeria. Collectively, worldwide prevalence of progeroid laminopathies is likely greater than progeria.
Lonafarnib, an oral farnesyltransferase inhibitor, has demonstrated extended survival in children and young adults with progeria. Lonafarnib has been granted Orphan Drug designation for Progeria and progeroid laminopathies by the U.S. Food and Drug Administration and the European Medicines Agency, and Breakthrough Therapy designation and Rare Pediatric Disease designation by the FDA. The FDA agreed that the Lonafarnib submission could be a rolling application, allowing completed portions of an NDA to be submitted and reviewed by the FDA on an ongoing basis. Eiger said it plans to complete the application in the first quarter of 2020.