Vertex Pharmaceuticals stepped forward this week and said it received FDA’s first two breakthrough drug designations, and will use the designations to expand uses for its landmark cystic fibrosis drug Kalydeco, ending widespread speculation about which company received the initial designations enacted by the FDA Safety and Innovation Act. The drug, although approved before the new program existed, was seen as an example of the type of product that could be a breakthrough candidate, according to a stakeholder who backed the program’s inclusion in FDASIA.
Kalydeco, known generically as ivacaftor, was approved about a year ago for patients 6 years and older with the G551D mutation in the cystic fibrosis transmembrane regulator (CFTR) gene. Of the 30,000 people with cystic fibrosis in the United States, 4 percent — about 1,200 people — are believed to have this mutation, said FDA upon approval. Vertex says it is exploring development strategies that, if successful, could treat up to 90 percent of cystic fibrosis patients worldwide.
Vertex seeks to expand the drug’s use in multiple ways, with two strategies receiving the breakthrough designation. The company is studying Kalydeco alone in patients with other gene mutations and in combination with another treatment, VX-809. The combination therapy would be studied in people with two copies of the F508del mutation, which is the most common cystic fibrosis mutation, the company said.
Vertex said the company presented clinical data in both cases.
“The designation for ivacaftor was based on data from clinical and pre-clinical studies, including Phase 3 data in people with the G551D mutation and pre-clinical data in the G551D mutation as well as a number of other mutations,” according to a company statement.
“The Breakthrough Therapy Designation for the combination regimen of VX-809 with ivacaftor was based on the Phase 2 combination data announced in 2012. Multiple studies are currently underway in an effort to determine whether patients with other CFTR mutations may benefit from ivacaftor alone, and Vertex is also preparing to start a pivotal program of VX-809 in combination with ivacaftor in people who have two copies of the most common CF mutation (F508del).”
Kalydeco was viewed as an example of a breakthrough drug as stakeholders set out to advocate for the new pathway, said Jeff Allen, executive director of Friends of Cancer Research. The group, which pressed for the breakthrough pathway’s inclusion in FDASIA, did a historic review of drugs that could be considered breakthrough. Kalydeco had several breakthrough characteristics, including that it was seen as a “game changer” for a debilitating disease, Allen said.
“I think Kalydeco is an example where it has altered the course of medical practices,” he said. There is consensus around the success of the molecule, therefore the designation is a “good way to acknowledge this is the effect we are looking for,” he said, noting that other companies will likely be reading into the agency’s decision making in this initial action.
The breakthrough pathway is intended to speed up the development and review of treatments for serious or life-threatening diseases and improve upon existing therapies. FDA officials said they intend to hold frequent meetings with companies developing drugs with this designation.
FDA granted the designations shortly after the law passed, signaling the agency’s intention to take advantage of the new program, Allen said. “The fact that they were willing to grant the designations so quickly I think should be seen as a sign they want to use this tool,” he said.
As of mid-December, FDA officials said they granted two breakthrough designations, denied one and had four pending. They emphasized the need for companies to present clinical data when pursuing the designation. Further, drug center officials have expressed concern that companies would have problems quickly scaling up production once approved under the new expedited pathway. FDA plans to release guidance on breakthrough and other expedited drug development pathways.
A lawmaker who backed the breakthrough’s inclusion in FDASIA lauded the new designations. “These breakthrough designations are welcomed news for patients who live their daily lives suffering from cystic fibrosis and are waiting to learn if potential new treatments can help them,” Sen. Michael Bennet (D-CO) said in a statement. “Now, FDA will work with Vertex to move these potentially lifesaving treatments through the FDA’s approval process quickly and safely — and hopefully they’ll be in the hands of patients in the near future. Our goal for the breakthrough designation is that it will help bring more and more lifesaving cures to patients more efficiently than ever before.”