Lonafarnib is in clinical development for the treatment of Hutchinson-Gilford Progeria syndrome (HGPS) and other progeroid laminopathies (PL). Progeroid laminopathies are characterised by the premature appearance of certain signs of physiological ageing in a subset of tissues, and the most prevalent of these rare diseases is HGPS. HGPS is caused by genetic abnormalities in a gene, which produces a protein called lamin A that helps to keep cells of the body strong and stable. HGPS is a severe and life-threatening condition which leads to premature death, primarily due to cardiovascular morbidities, such as heart attacks and strokes. The mean life expectancy in progeria is 14.5 years of age.
Lonafarnib, administered orally, works by preventing the formation of abnormal lamin A. An abnormal quantity of lamin A causes overproduction of a defective protein called progerin, which is believed to cause premature ageing in children. If licensed, lonafarnib will provide the first and only approved treatment option for patients with HGPS and PL.