FDA Approves Lumacaftor/Ivacaftor for Younger Children with Cystic Fibrosis

The US Food and Drug Administration (FDA) has approved the first therapy designated for the treatment of the underlying cause of cystic fibrosis (CF) in certain pediatric patients aged 2-5 years.

Vertex Pharmaceuticals’ lumacaftor/ivacaftor (ORKAMBI) has been approved for use in the childhood age group of patients with 2 copies of the F508del-CFTR mutation, the most common genetic form of CF which affects approximately 1300 specific patients in the US.

The oral granule therapy was approved in 2 different weight-based dosing strengths: lumacaftor 100mg/ivacaftor 125mg and 150mg/188mg. The therapy should be available for fulfillment within 2-4 weeks, according to Vertex.

The combination drug works to increase mature protein prevalence at the cell surface (lumacaftor) by processing and trafficking the F508del CFTR protein defect, and enhancing the function of the CFTR protein (ivacaftor) once it reaches the cell surface.

Lumacaftor/ivacaftor was previously approved by the FDA for children aged 6 years or older with CF and 2 copies of the F508del-CFTR mutation. This newest indication was based on a phase 3 open-label safety trial of 60 patients, in which the treated younger patients showed a safety and tolerability profile similar to that in patients ages 6 years and older.

Researchers had observed mean decrease of 31.7 mmol/L (95% CI; -35.7 - -27.6) in sweat chloride at week 24 from baseline, as well as changes in key growth parameters.

According to the findings, presented at the 41^st European Cystic Fibrosis Society Conference in June, the most common adverse event (AE) prevalent in at least 30% of the patient population was cough (63%). Just 4 patients reported serious AEs; 2 being pulmonary exacerbations, and the others being gastroenteritis and constipation. Three patients discontinued treatment due to AEs or elevated liver function tests.

As characterized by poor salt and water flow into multiple organ cells which leads to the formation of mucus, CF can cause chronic, progressive lung infection and damage that results in median patient death in their mid-20s. Fighting it from its earliest presence can make a major difference for clinicians, John McNamara, MD, lead study researcher, said.

“This approval is a significant development that enables physicians to begin treating the underlying cause of the disease in this population earlier than ever before,” McNamara said.

Reshma Kewalramani, MD, executive vice president and chief medical officer at Vertex, emphasized the significance of treating this 1300-patient population in the US.

“We believe it is important to treat the underlying cause of the disease as early as possible and this approval is another significant milestone in our journey to bring effective medicines to all people living with CF,” Kewalramani said in a statement.