PEABODY, Mass.—The Progeria Research Foundation (PRF) has initiated a rolling submission of a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) by Eiger BioPharmaceuticals, Inc., seeking approval of lonafarnib — the first-ever treatment for Progeria and Progeroid Laminopathies. Eiger plans to complete the submission in the first quarter of 2020.
“It is incredibly exciting to see twelve years of clinical data translate into the initiation of this NDA submission,” said Leslie Gordon, M.D., Ph.D., PRF medical director. “Since day one of the Progeria Research Foundation, we have been working toward treatments and the cure for this rare, fatal condition. This submission—the first for the treatment of Progeria—is a big milestone in that mission.”
Lonafarnib, a farnesyltransferase inhibitor (FTI), has demonstrated extended survival in children and young adults with Hutchinson-Gilford Progeria Syndrome (HGPS), or Progeria, an ultra-rare and fatal disease that causes premature aging in children. Without treatment, children with Progeria die of heart disease at an average age of 14.5 years.
Progeria is caused by a random genetic mutation that produces an overabundance of the progerin protein. Approximately 400 children worldwide have Progeria. In normal human aging, the accumulation of some progerin within a cell is common, but in Progeria the rate of accumulation is highly accelerated, resulting in progressive cellular damage and atherosclerotic heart disease.
Lonafarnib inhibits farnesyltransferase, an enzyme that facilitates progerin production. The FTI is thought to prevent the mutant protein from absorbing into the cellular wall where it causes much of its damage, reversing instability of the nuclear structure.
Since 2007 PRF has funded and led four clinical trials to study lonafarnib’s effect on Progeria, treating children from over 30 countries. Researchers from Boston Children’s Hospital and Brown University have tracked over 250 children from six continents, demonstrating a link between lonafarnib treatment and extended survival. Results from a 2018 study published in The Journal of the American Medical Association demonstrated that treatment with lonafarnib alone compared with no treatment was associated with a significantly lower mortality rate (3.7% vs. 33.3%) after a median of 2.2 years of follow up.
“Throughout our 20-year history, we've made tremendous progress in our understanding and treatment of Progeria, leading us to this historic achievement. PRF is grateful to the families and children with Progeria who have participated — some traveling thousands of miles to Boston — in our clinical trials, to the clinical investigators at Boston Children’s Hospital and Brown University, and to Eiger,” noted Audrey Gordon, president and executive director of the Progeria Research Foundation. “We have worked tirelessly to make a meaningful impact on the lives of children and young adults with Progeria, and this submission brings us closer to that goal.”