The European Union’s Committee for Medicinal Products for Human Use (CHMP) has issued a positive recommendation for Orkambi (ivacaftor/lumacaftor) as a therapy for cystic fibrosis (CF) in children. The ruling is specifically for pediatric patients aged 6 to 11 with two copies of the F508del mutation in the CFTR gene.
CF, an inherited disease, affects about 12,000 people aged 12 years and older in Europe, and more than 30,000 people in the United States. It is caused by a defective or absent CFTR protein, the result of mutations in the CFTR gene. Having two copies of the F508del mutation in the CFTR gene — one from each parent — is the leading cause of CF.
This mutation results in little to no CFTR protein at the cell surface, where it controls water flow and helps ions enter and leave the cell. This leads to poor flow of salt and water into and out of the cell in several organs, a buildup of thick and sticky mucus inside the body, and very salty perspiration. This can cause severe respiratory and digestive problems, as well as infections.
Orkambi is a combination therapy developed by Vertex Pharmaceuticals that helps CF patients produce thinner mucus. It consists of lumacaftor (VX-809) and Kalydeco (ivacaftor). Lumacaftor helps transport CFTR protein to the cell surface, and Kalydeco helps activate CFTR protein once it reaches the surface.
Orkambi already has U.S. and EU approval for CF patients aged 12 and older with two copies of the F508del mutation in the CFTR gene. Last year, it received approval from the U.S. Food and Drug Administration (FDA) to treat CF patients aged 6 to 11, following positive results in a Phase 3 trial of children.
That trial (NCT02514473) evaluated the effect of Orkambi in 103 children aged 6 to 11 (200 mg lumacaftor and 250 mg Kalydeco, every 12 hours) compared to that of placebo (101 children) for 24 weeks. Orkambi significantly improved lung function, the ability to clear mucus from the lungs, and the amount of chloride ions eliminated through sweating, compared to placebo.
Concerning safety, the trial revealed a similar safety profile to that observed in previous Phase 3 studies of children. The most commonly reported adverse reactions were mild to moderate, and included cough, pulmonary exacerbation, fever, headache, nasal congestion and upper respiratory tract infection.
“Cystic fibrosis is a systemic, multi-organ, progressive disease present from birth,” David Gillen, head of international medical affairs at Vertex, said in a press release. “This recommendation brings us closer to being able to help more people with CF who currently do not have a medicine to treat the underlying cause of their disease.”
The European Commission will now make a final decision on whether to approve the therapy among 6-to-11-year-olds. The commission usually follows the CHMP’s recommendations.