FDA Approves Combination Therapy for Cystic Fibrosis

The U.S. Food and Drug Administration (FDA) approved tezacaftor/ivacaftor and ivacaftor (Symdeko) for the treatment of the underlying cause of cystic fibrosis (CF) in people ages 12 years and older who have 2 copies of the F508del mutation in the CF transmembrane conductance regulator (CFTR) gene, or who have at least one mutation that is responsive to the combination therapy.

Vertex, the developer of the drug, announced the news last night and has stated its intentions to launch the drug and begin shipping to United States pharmacies this week.

In the fourth quarter of 2017, the New England Journal of Medicine published results from two Phase 3 trials — EVOLVE and EXPAND – evaluating the safety and efficacy of tezacaftor in combination with ivacaftor in patients with CF. Across both studies, patients treated with the drug experienced statistically significant and clinically meaningful improvements in lung function and other measures of the disease, with a favorable safety profile.

“Today is an exciting day for the CF community. The approval of SYMDEKO, our third disease-modifying CF medicine, offers many patients an important new treatment option,” said Jeffrey Leiden, M.D., Ph.D., Vertex's Chairman, President and Chief Executive Officer in a press release. “This approval is an important milestone in our journey to treat every person with CF, and we remain committed to urgently advancing our efforts to develop new medicines that treat the underlying cause of CF for the many people still waiting.”

The F508del mutation has been known to lead to substantially reduced CFTR protein activity and a complete loss of chloride secretion, which can result in impaction of mucus in the airways, gastrointestinal (GI) tract, and exocrine organs. It also has the potential to cause severe clinical consequences, like gradual loss of lung function, nutritional deficits, pulmonary exacerbations, and respiratory failure.

It is the most prevalent CFTR mutation worldwide, and an estimated 46% of American CF patients are affected by it.

In the combination, tezacaftor is designed to address the trafficking and processing defect of the CFTR protein to permit it to reach the cell surface, while ivacaftor can increase the amount of time that the protein stays open.

The most commonly experienced adverse events (AEs) among the enrolled patients included infective pulmonary exacerbation, cough, headache, nasopharyngitis, increased sputum production, pyrecia, hemoptysis, oropharyngeal pain, and fatigue. No severe side effects were reported, and the safety profile of the tezacaftor/ivacaftor combination supports its use in a broad range of patients.

With the approval, tezacaftor/ivacaftor becomes the third of Vertex’s drugs approved for CF patients, and the second intended specifically to treat patients with this specific mutation.

“We’ve already seen the significant impact that disease-modifying medicines can have on patients and are incredibly pleased that there is now a third treatment option that enables more patients to benefit from CFTR modulation,” said Patrick Flume, M.D., Director of the Medical University of South Carolina Cystic Fibrosis Center and Principal Investigator for the EXTEND study. “In particular, SYMDEKO is an important treatment option for patients who either never started or discontinued ORKAMBI, and it also provides increased benefit over KALYDECO alone for patients with residual function mutations.”

Vertex is dedicated to helping patients with CF, and has initiated The Vertex Guidance & Patient Support (Vertex GPS) program to provide a team of company employees to assist patients understand insurance benefits and the resources that are available to help them.

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