Eiger Biopharma announced it has initiated submission of a New Drug Application (NDA) to the FDA under the Rolling Review Process. The company is seeking approval for lonafarnib for the treatment of Hutchinson-Gilford Progeria Syndrome (HGPS or Progeria) and Progeroid Laminopathies. The Rolling Review NDA process allows for portions of an NDA to be submitted and reviewed by the FDA on an ongoing basis. Eiger plans to complete the NDA rolling submission in first quarter of 2020.
Lonafarnib has been dosed in over 80 children with Progeria at Boston Children’s Hospital in Phase 1/2 and Phase 2 studies funded by The Progeria Research Foundation. In patients with HGPS, lonafarnib monotherapy was associated with a lower mortality rate after 2.2 years of follow-up compared with no treatment (3.7% vs 33.3%, respectively) with a hazard ratio of 0.12 or a reduction in risk of mortality of 88%.
Lonafarnib has been granted Orphan Drug Designation for Progeria and Progeroid Laminopathies by the FDA and EMA and Breakthrough Therapy Designation and Rare Pediatric Disease Designation by the FDA.
Progeria, also known as Hutchinson‐Gilford Progeria Syndrome (HGPS), is a rare and fatal genetic condition of accelerated aging in children. Progeria 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.
About Progeroid Laminopathies
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 is an orally active inhibitor of farnesyltransferase, an enzyme involved in modification of proteins through a process called prenylation. Progerin is a farnesylated aberrant protein that researchers believe cannot be cleaved, resulting in tight association with the nuclear envelope, which leads to changes in nuclear envelope morphology and subsequent cellular damage.