FDA Expands Orphan Drug Indication Based on Lab Tests

James Radke
Published Online: Wednesday, May 17, 2017
Today, the FDA expanded the approved use of Kalydeco (ivacaftor) from patients with 1 of 10 mutations on their cystic fibrosis transmembrane conductance regulator (CFTR) gene to patients with 1 of 33 mutations. 

Based on the new expansion, Vertex Pharmaceuticals has increased their predicted revenue for Kalydeco to over $740 million. The drug is now indicated for more than 900 people in the United States.
Unlike past approvals, the expansion is not based on new pivotal clinical trials, but rather on the results of laboratory testing in conjunction with data from earlier human clinical trials.
In a news release, Janet Woodcock, M.D., director of the FDA’s Center for Drug Evaluation and Research justified this novel approach and said, “Many rare cystic fibrosis mutations have such small patient populations that clinical trial studies are not feasible……This challenge led us to using an alternative approach based on precision medicine, which made it possible to identify certain gene mutations that are likely to respond to Kalydeco.”
People with cystic fibrosis (CF) often have a mutation on their CFTR gene but since there are so many mutations, it is difficult to justify doing new clinical trials for each subpopulation of patients with specific mutations. Per the FDA, the results from an in vitro cell-based model system have been shown to reasonably predict clinical response to Kalydeco.
CF is a rare condition in which defective or missing CFTR protein results in poor flow of salt and water across cell membranes and the effects are particularly problematic in the lungs.  There is a buildup of thick, sticky mucus that can cause chronic lung infections and progressive lung damage. The median predicted age of survival for a person born today with cystic fibrosis is 41 years.
Kalydeco (ivacaftor) is a CFTR potentiator that is designed to keep CFTR proteins at the cell surface open longer to improve the transport of salt and water across the cell membrane.

Image courtesy of the FDA.

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