Vertex Pharma is celebrating after the FDA once again extended the labelling for its cystic fibrosis therapy Kalydeco so that more patients with the genetic disease are eligible to use it.
The new indication more than triples the number of CF transmembrane conductance regulator (CFTR) gene mutations that Kalydeco (ivacaftor) can now treat, from 10 to 33, making the drug an option for another 900 people in the US with CF caused by rare ‘residual function mutations’.
The US regulator took the decision on the strength of laboratory data as running a clinical trial involving people with these mutations was not feasible according to Janet Woodcock, director of the FDA’s Center for Drug Evaluation and Research (CDER).
“This challenge led to us using an alternative approach based on precision medicine, which made it possible to identify certain gene mutations that are likely to respond to Kalydeco,” she said. The agency first gave a green light to Kalydeco in 2012, approving it for use in around 1,200 CF patients, with subsequent label extensions taking that total to around 2,000 patients in the US and 4,000 internationally.
Vertex says the new labelling – which was initially turned down by the FDA – could increase sales of Kalydeco this year from around $740m to $770m, adding that it is also in discussions with the FDA about getting approval for another 600 people who have additional mutations including one of five ‘splice’ mutations.
The company is hopeful of a positive outcome, as these five mutations were evaluated as part of the phase III EXPAND study in which Kalydeco met its primary efficacy endpoint.
The FDA verdict could also boost Vertex’s follow-up CF combination therapy Orkambi (ivacaftor and lumacaftor), which was launched in 2015 and has already overtaken its predecessor in sales terms, bringing in $980m to Kalydeco’s $703m last year.
Meanwhile Vertex reported positive phase III data in March for another two-drug combination for CF – ivacaftor and tezacaftor – in people who have one mutation that results in residual CFTR function and one F508del mutation. The new therapy will be filed for approval in both the US and Europe in the third quarter of this year.