Children's Colorado participates in cystic fibrosis triple combination therapy trials

Children's Hospital Colorado (Children's Colorado) has announced that its Mike McMorris Cystic Fibrosis Research and Care Center, one of the largest cystic fibrosis (CF) clinical care centers in the U.S., is participating in one of two Phase Three clinical trials related to the development of a possible breakthrough therapy for people with CF. Phase Three trials are generally the last round of trials before possible FDA approval of a new drug.

The studies are examining the potential for two compounds - currently known as VX-659 and VX-445 - to be used as part of a triple combination modulator therapy for CF. CF is caused by a mutation in a single gene called the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR). The most common of these mutations is known as an F508del mutation. CFTR modulator therapies are designed to correct the malfunctioning protein made by the mutated CFTR gene.

Specifically, Children's Colorado is participating in the Phase Three study of VX-659 combined with tezacaftor/ivacaftor (SymdekoTM) for people with CF ages 12 years and older with one F508del mutation and another "minimal function" mutation. Currently, no CFTR modulator is available for this patient population.

"Different mutations cause different defects in the protein produced by the CFTR gene, and the medications that have been developed so far - such as Orkambi®, Kalydeco ® and Symdeko™ - are effective only in people with specific mutations," said Edith Zemanick, MD, pediatric pulmonologist at Children's Colorado. "What is really exciting about these Phase Three trials is the prospect of developing a combination therapy to treat people with a single F508del mutation. This would mean that more people than ever before could benefit from modulator therapies."

The announcement of the Phase Three trials comes on the heels of the FDA's approval of Symdeko (tezacaftor/ivacaftor) in February. The combination drug was approved for use in patients ages 12 and older with two copies of the F508del mutation or one of 26 other specified mutations, even if they do not have a copy of the F508del mutation. Children's Colorado participated in some of the Phase Three trials of this drug and is currently conducting a study of the drug in children ages six to 11.

"We have been involved in CF clinical trials with Children's Colorado since our son was little," said Libby Colbert, mother of Noah, 12, a patient at Children's Colorado. "He started taking the drug right after its approval by the FDA, and we saw a difference almost immediately. The combination of tezacaftor and ivacaftor has been a great medicine for Noah and has helped him smell and breathe better. We are grateful to live close to a great hospital where Noah is receiving exceptional care and is among leaders in CF research. This is a great step for all those living with CF and we are excited for this milestone in medicine."