4 September 2018 - - US-based rare disease specialist Eiger BioPharmaceuticals, Inc. (NASDAQ: EIGR) has received minutes from a pre-investigational new drug (pre-IND) meeting with the Division of Gastroenterology and Inborn Errors Products of the US Food and Drug Administration for lonafarnib in the treatment of Hutchinson-Gilford Progeria Syndrome (HGPS or Progeria), the company said.

Eiger plans to submit a new drug application in 2019.

There is no approved treatment for Progeria, an ultra-rare and fatal genetic condition characterized by accelerated aging in children.

Eiger and the FDA engaged in a collaborative discussion regarding the analysis methodology for the survival data that was published in April 2018 Journal of the American Medical Association as potential support for submission of an NDA filing.

This clinical study, which compared children with Progeria who received lonafarnib monotherapy with matched untreated children with Progeria, reported a primary outcome of mortality.

The study found that children taking lonafarnib monotherapy experienced a 77% reduction in the risk of mortality compared to a natural history, matched-control cohort of untreated children after two years of study.

Based on this meeting with the FDA, Eiger does not anticipate conducting additional clinical efficacy studies to complete the filing for registration.

Clinical studies with lonafarnib in Progeria were funded by The Progeria Research Foundation.

Eiger has supplied lonafarnib for investigational use in Progeria clinical studies since 2015, and is now responsible for development, regulatory, commercialisation and distribution activities for lonafarnib in Progeria.

Progeria, also known as Hutchinson-Gilford Progeria Syndrome, is a rare and rapidly fatal genetic condition of accelerated aging in children caused by a point mutation in the lamin A gene yielding the farnesylated aberrant protein, progerin.

Lamin A protein is the structural scaffolding that holds the nucleus together. Researchers now believe that defective lamin A protein makes the nucleus unstable, and that cellular instability leads to the process of premature aging in Progeria.

Children with Progeria die of the same heart disease that affects ms 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 350 children worldwide have Progeria.

Lonafarnib is a well-characterised, late-stage, orally active inhibitor of farnesyltransferase, an enzyme involved in modification of proteins through a process called prenylation.

Progerin is a farnesylated protein that cannot be cleaved, resulting in tight association with the nuclear envelope, which in turn results in changes in nuclear envelope morphology and subsequent cellular damage.

Lonafarnib blocks the farnesylation of progerin and has been dosed in over 80 children with Progeria at Boston's Children Hospital in multiple Phase 1/2 and Phase 2 studies. Lonafarnib has been granted Orphan Drug Designation for Progeria by the FDA. Lonafarnib is not approved for any indication, and is licensed by Eiger from Merck Sharp and Dohme Corp.

The Progeria Research Foundation was established in 1999 by the family of Sam Berns, a child with Progeria. Within four years of its founding, the PRF Genetics Consortium, led by Francis Collins, MD, PhD, discovered the Progeria gene.

PRF has also been the driving force behind studies to evaluate lonafarnib as a potential treatment for Progeria and supports scientists who conduct Progeria research.

Currently, PRF is the only non-profit organisation in the world solely dedicated to finding treatments and the cure for Progeria and its age-related conditions, including heart disease.

Eiger is a clinical-stage biopharmaceutical company focused on the development and commercialization of targeted therapies for rare diseases.