Vertex’s future riding on CF combination

A new two-drug combination to treat cystic fibrosis has been filed in Europe and the US by Vertex, and could expand greatly the number of patients with the life-limiting disease who could benefit.

News of the filing is a key moment for the company, and for patients with cystic fibrosis, as if approved, the combination could expand those benefitting from 3,000 patients worldwide to 28,000 or more.

The company launched its groundbreaking treatment Kalydeco (ivacaftor) in 2012, the first ever treatment for cystic fibrosis (CF) to directly target the underlying mechanism of the disease, caused by a cluster of defects in the in the cystic fibrosis conductance regulator (CFTR) gene.

However Kalydeco only helps a subset of patients, and is licensed to help patients with the G551D mutation, who account for just 4-5 per cent of patients, around 3,000 patients worldwide.

But now a combination of Kalydeco and another Vertex-developed agent, lumacaftor has shown to be effective in treating a larger sub-group, those with two copies of the F508del mutation, the most common form of the disease.

Phase 3 clinical trial results for the combination of the two drugs were promising, and address a huge unmet medical need – patients must battle often life-threatening lung infections, and see their lung function decrease year by year.

The drugs do not represent a cure for the disease, but the Phase 3 studies showed they significantly improved the lives of patients by increasing their lung function and reducing their pulmonary exacerbations caused by infections.

The promise of the combination means the FDA and the EMA regulators have given the combination their respective Breakthrough and Accelerated Assessment designations.

The submissions are based on two global Phase 3 studies, TRAFFIC and TRANSPORT in patients aged 12 and older who have two copies of the F508del mutation treated with standard-of-care medicines. The studies showed improvements in lung function and other measures of disease, such as pulmonary exacerbations, through 24 weeks of combination treatment. Initial interim data from a further rollover study showed that lung function improvements were sustained for 48 total weeks of treatment, and that it was generally well tolerated.

In June when these results emerged, ISI Group analyst Mark Schoenebaum said the data should secure approval, and he forecast global peak sales in excess of $3 billion.

The high cost of Kalydeco has caused controversy, particularly in the US where it costs around $300,000 for a year’s treatment per patient.  Vertex has not disclosed its plans for the cost of the combination treatment, but this will clearly be a major hurdle for the firm and healthcare payers and patients if and when it is approved. 

The success of ivacaftor + lumacaftor is vital to the company because it is still in the red: results for the first nine months of 2014 showed a loss of over $500 million. The company’s finances have been made worse by the steep decline in sales of its hepatitis C product Incivek, which was once a major earner for the company. Incivek has been made virtually obsolete by the arrival of Gilead’s Sovaldi this year, and Vertex withdrew the drug from the market last month.

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