New CF Drug Targets Protein

Vertex Pharmaceuticals, a Cambridge-based pharmaceutical company, received FDA approval last week for its new cystic fibrosis treatment. While all previous CF treatments have fought the disease by mitigating its symptoms, this treatment fights the disease by remedying the cause.

Kalydeco, Vertex’s CF therapy, fights a branch of CF caused by a particular mutation found in approximately 1,200 people in the United States, 1,000 in the EU, and 180 in Ireland—areas where the mutation is most prevalent. Kalydeco functions by binding to the protein deformed by the CF mutation and helping it open properly to regain its normal function.

This treatment is a major development in the treatment of CF—a fatal genetic disorder caused by mutations that deform or destroy proteins responsible for regulating salt and water flow in many cells. The protein’s loss of function results in a characteristic buildup of thick, sticky mucus in the respiratory pathway that may cause chronic lung infections and long-term respiratory damage.

“We’re extremely happy with the results, and we’re especially happy for the patients,” said Chris I. Wright ’87, senior vice president and head of global medicines development and affairs at Vertex. “This represents a transformation in the care of the subset of the patients that have CF. We’re happy with the way this drug has been able to improve their lives.”

As an example of personalized medicine, Wright said this treatment is a “very highly targeted therapy.”


“The drug was specifically developed to target the defective protein in that particular subset [of patients],” he continued.

Vertex received FDA approval for Kalydeco relatively quickly, by FDA standards. Wright said the FDA’s speedy approval can be credited to the profundity of Kalydeco’s approach and its “excellent clinical data.”

Patients could breathe more easily, exhale more easily, and there was a 55 percent reduction in emergency-level respiratory changes, which reduced hospital visits. Patients on Kalydeco also experienced weight gain, offsetting the weight loss common among CF patients.

Wright also emphasized the novelty of the treatment, noting, “This is really the first medication that treats the underlying cause of the disease. Other treatments out there treat the symptoms, such as bronchodilators, but this treats the cause. It completely changes the paradigm of how to treat this disease.”

Mihaela G. Gadjeva is assistant professor of medicine at Brigham and Women’s Hospital. On the development of Kalydeco, Gadjeva said, “it seems to be very promising in bringing clinical results.”

While Gadjeva acknowledged that Kalydeco directly helps only a small portion of the CF patient population, she said that it opens the door to new treatments and that “it is a great step forward in providing CF patients with some form of treatment.”

Vertex’s current goal, besides quickly distributing Kalydeco to patients in need, is to develop cures for other CF-causing gene mutations using the Kalydeco approach. Wright said that Vertex is now studying a different mutation which plays a role in approximately 90 percent of CF patients.

—Staff writer Daniel J. Kramer can be reached at