EC grants marketing authorisation for Vertex’s ORKAMBI cystic fibrosis drug

In Europe, there are approximately 12,000 people with CF ages 12 and older who have two copies of this mutation. Vertex will now begin the country-by-country reimbursement approval process across the European Union (EU).

Stuart Elborn, M.D., Dean, School of Medicine, Dentistry and Biomedical Sciences at Queen’s University Belfast, and a lead Principal Investigator for the Phase 3 TRAFFIC study, said: "For people with cystic fibrosis, the disease is a lifelong battle that becomes progressively more serious with repeated hospitalization due to lung infections. Until now, people with two copies of the F508del mutation have only had treatments for the symptoms and complications of the disease.

"The combination of lumacaftor and ivacaftor represents a step-change in the management of cystic fibrosis for these patients because it addresses the underlying cause of the disease. By doing so, it has shown meaningful and sustained benefits."

Today’s approval is based on previously announced data from two 24-week global Phase 3 studies, TRAFFIC and TRANSPORT, and additional interim 24-week data from the subsequent extension study, PROGRESS, in people ages 12 and older who have two copies of the F508del mutation and were already being treated with standard-of-care medicines.

In the TRAFFIC and TRANSPORT studies, which enrolled more than 1,100 patients, those treated with the combination of lumacaftor and ivacaftor experienced significant improvements in lung function.

Patients also experienced improvements in body mass index (BMI) and reductions in pulmonary exacerbations (acute lung infections) including those requiring hospitalizations and intravenous antibiotic use. Interim data from PROGRESS showed that these improvements were sustained through 48 total weeks of treatment (24 weeks in TRAFFIC/TRANSPORT + 24 weeks in PROGRESS).

In addition, the pattern and magnitude of response observed after the initiation of combination treatment across all patients who received placebo in TRAFFIC and TRANSPORT and subsequently received a combination regimen in PROGRESS were similar to those seen among patients who received a combination regimen in TRAFFIC and TRANSPORT.

The combination of lumacaftor and ivacaftor was generally well tolerated in all three studies. In TRAFFIC and TRANSPORT, the most common adverse events included shortness of breath and/or chest tightness, upper respiratory tract infection (common cold) and gastrointestinal symptoms (including nausea, diarrhea, or gas).

In the extension study, the safety and tolerability results, including the type and frequency of adverse events and serious adverse events, were consistent with those observed in TRAFFIC and TRANSPORT, and no new safety concerns were identified.

Over 48 weeks, the most common adverse events were infective pulmonary exacerbation, cough and increased sputum. The incidence of serious adverse events during PROGRESS was generally similar to TRAFFIC and TRANSPORT.

Vertex chairman, president and CEO Jeffrey Leiden said: "The EU approval of lumacaftor in combination with ivacaftor is a major milestone in our longstanding efforts to develop new medicines that treat the underlying cause of the disease for people with cystic fibrosis.

"This has been 17 years in the making and is the result of a collaborative effort with the CF community. Our goal now is to help ensure that those who need this medicine can get it, and to continue our work for the two out of three people with cystic fibrosis in Europe who still don’t have a treatment that addresses the underlying cause of their disease."