A combination of Vertex Pharmaceuticals Inc's cystic fibrosis drug Kalydeco and its experimental lumacaftor succeeded in improving lung function in a pair of closely watched late-stage trials of patients with the most common genetic mutation associated with the rare lung disease.
In the two, 24-week studies of patients 12 years and older with two copies of F508del genetic mutation, the combination therapy led to mean absolute improvements in lung function of between 2.6 and 4 percentage points, which was deemed to be statistically significant, the company said on Tuesday.
The results are seen as critically important to Vertex, which is likely to need approval of the combination therapy to return to profitability.
"(The data) opens up 28,000 F508Delta patients, giving Vertex a multi-billion dollar franchise and essentially a monopoly for years," Maxim Group analyst Jason Kolbert told Reuters.
Kalydeco is approved to treat cystic fibrosis (CF) patients with a different genetic mutation that accounts for about 2,000 patients worldwide, or about 4 percent of the CF population. It had sales of $371 million in 2013.
Almost half of all CF patients aged 12 and over have the two copies of the F508del mutation.
Cowen and Co, in a research note last week, said a 3 percent absolute difference in lung function would be "a minimally clinically meaningful benefit."
Lung function improvement was measured by FEV1, or the amount of air a patient can exhale in one second. All four combination treatment arms of the studies called Traffic and Transport achieved the primary goal of mean absolute improvement in FEV1 compared with a placebo, Vertex said.
Based on the results, the company said it would file applications for U.S. and European approval for the combination in the fourth quarter.
The mean relative improvements in lung function seen for patients from baseline measurements was 4.3 percent to 6.7 percent, the company reported.
A pooled analysis of data from the two trials also showed significant reductions of between 30 and 39 percent in the rate of pulmonary exacerbations, or acute worsening of symptoms, for those who got the two drugs compared with the placebo groups.
Patients who received the combination also experienced small but statistically significant increases in body mass index. Weight gain is seen as a beneficial effect as CF patients have trouble gaining weight.
Kalydeco (ivacaftor) and lumacaftor address the underlying cause of CF rather than just symptoms of the disease, in which a missing or defective protein called CFTR results in poor flow of salt and water into and out of cells in the lungs. That causes a buildup of thick, sticky mucus that can lead to chronic lung infections, progressive lung damage and death at an early age.
"On average, people with CF who have two copies of the F508del mutation lose nearly two percent of their lung function each year, underscoring the urgent need for new medicines that address the underlying cause of this disease," Dr. Bonnie Ramsey, lead investigator of one of the studies, said in a statement.
The two studies involved a total of about 1,100 patients with each trial having two active treatment dosing regimens and a placebo group.
Among those who received the combination, 4.2 percent dropped out of the studies due to adverse side effects compared with a 1.6 percent dropout rate in the placebo group. The most common adverse side effects were infective pulmonary exacerbation, cough, headache and increased sputum.
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