The FTI Drug Lonafarnib

The FTI lonafarnib – the first and only known drug treatment for children with Progeria

In August 2005 and February 2006, researchers published studies that supported a potential drug treatment for children with Progeria. Farnesyltransferase inhibitors (FTIs), originally developed to potentially treat cancer, reversed the dramatic nuclear structure abnormalities that are the hallmark of cells from children with Progeria. In addition, this FTI drug improves some signs of disease in a Progeria-like mouse model.

Why did researchers think this drug would work in Progeria? The protein that we believe is responsible for Progeria is called progerin. In order to block normal cell function and cause Progeria, a molecule called a “farnesyl group” must be attached to the progerin protein. FTIs act by blocking (inhibiting) the attachment of the farnesyl group onto progerin.  So if the FTI drug can block this farnesyl group attachment in children with Progeria, then progerin may be “paralyzed” and Progeria improved.

For the first time, we had in front of us a possible treatment for children with Progeria. A first-ever clinical drug trial began in 2007, and in 2012 the study results were published, demonstrating that every child experienced improvement in one or more areas, including the vital cardiovascular system.  In May 2014, further study revealed lonafarnib increases estimated lifespan by at least 1.6 years (time will tell if that number increases – it just hasn’t been long enough to determine) and in April 2018 a study published in The Journal of the American Medical Association (JAMA) reported that lonafarnib alone extended survival in children with Progeria.  Click here for details on the 2012 study, here for details on the 2014 findings, and here for details on the 2018 study.

In May 2018, on the heels of the study published in JAMA, PRF and Eiger Biopharmaceuticals entered into collaboration and supply agreement for the development and pursuit of U.S. Food and Drug Administration review and potential approval of lonafarnib for the treatment of Progeria in children. Lonafarnib will mark the first therapy submitted to the FDA for the treatment of Progeria.

We now have one treatment for Progeria but it is not a cure, so we continue to drive the research to discover drugs that will be even more effective, and ultimately cure Progeria.