Lonafarnib gets FDA nod for treatment of progeriaDecember 2, 2020
The US FDA has recently approved lonafarnib (Zokinvy) as the first-ever treatment for progeria, a rare and fatal paediatric disease, characterized by dramatic, rapid ageing beginning in childhood.
Progeria, also known as Hutchinson-Gilford progeria syndrome, is a multisystemic disease caused by a genetic mutation in the LMNA (“lamin A”) gene, which helps maintain the normal structure and function of a cell’s nucleus. About 400 children worldwide have been diagnosed with progeria.
Lonafarnib is a farnesyl transferase (FTase) inhibitor (FTI), which reduces the farnesylation of numerous cellular proteins, including progerin. As progerin farnesylation is important for localization to the nuclear membrane and lonafarnib inhibits progerin accumulation and improves symptoms in HGPS patients.
The drug has been approved for reducing risk of death from HGPS, as well as for the treatment of some processing-deficient progeroid laminopathies in patients 1 year and older.
Data based on information from the PRF International Patient Registry and clinical trials co-coordinated by PRF and Boston Children’s Hospital demonstrated that in patients with Progeria, lonafarnib reduced the incidence of mortality by 60% and increased average survival time by 2.5 years.
Without the treatment, children with progeria died of heart disease at an average age of 14.5 years. Eiger BioPharmaceuticals (Eiger) began supplying lonafarnib for the progeria clinical trials in 2015, and entered into a pioneering partnership with PRF in 2018 with the objective of leading lonafarnib through the FDA approval process.
Patients with the syndrome treated with lonafarnib reported an increased lifespan of 3 months through the first 3 years of treatment versus control—and an increase of 2.5 years through a maximum follow-up period of 11 years.
Lonafarnib’s approval for the treatment of certain, rare processing-deficient progeroid laminopathies was based on observed similarities in underlying genetic mechanisms of disease and other available data.
Commonly observed adverse events in the supporting-data trial included nausea, vomiting, diarrhoea, increased appetite, and fatigue. The FDA indicated that lonafarnib is contraindicated for co-administration with strong or moderate CYP3A inhibitors and inducers, as well as midazolam and certain cholesterol-lowering therapies.