- Cystic fibrosis patients on a three-drug regimen consisting of tezacaftor, ivacaftor and an experimental corrector known as VX-659 had significantly greater improvements in lung function than those who didn't, according to interim data from a pair of late-stage studies announced Tuesday.
- Vertex Pharmaceuticals, the company behind each of the drugs, said its triplet showed efficacy across two kinds of cystic fibrosis patients: those who are homozygous and have two F508del mutations, and those who are heterozygous and have one F508del mutation and one minimal function mutation. The most common mutation found in cystic fibrosis patients, F508del spurs the disease by messing up a protein that regulates how salt and water move in and out of cells.
- One of the Phase 3 trials found that after four weeks of treatment, the heterozygous patients who received Vertex's triplet had a 14% mean absolute improvement on a common lung function measurement called ppFEV1. The other trial found homozygous patients who received the triplet had a 10% mean absolute improvement on that measure compared to patients on a regimen of tezacaftor, ivacaftor and placebo.
While expected, the new positive data further cement Vertex's already leading position in the cystic fibrosis drug market. There, the Boston-based biotech has three products, Kalydeco (ivacaftor), Orkambi (lumacaftor/ivacaftor) and Symdeko (tezacaftor/ivacaftor), that collectively snagged $783 million during the third quarter.
Vertex estimates those drugs give it access to about 60% of cystic fibrosis patients. The company believes three-drug combination regimens and gene therapies will open the door to the remainder of the population, though the near-term focus is largely on the triplets.
"One of the things we've learned is that it's going to be a world of triples, and it's going to be a world of triples pretty quickly," Vertex CEO Jeffrey Leiden said on the company's third quarter earnings call.
"And the reason for that is that in order to really get to all patients — particularly the [heterozygous] patients who are so difficult to treat and to maximize benefit for the homozygous patients — it's pretty clear now that you need a triple,' he said.
Vertex's position is all the more advantageous given it has two Food and Drug Administration-approved doublets to use in clinical testing. What's more, the biotech has advanced both VX-659 and another next-generation corrector, dubbed VX-445, into late-stage triple-combination testing, thereby offering it multiple shots on goal.
It's a setup that has gone over well with investment banks. In a Nov. 27 note, Jefferies analyst Michael Yee wrote that Vertex is the "only big growth story in large-cap biotech, making it a scarce equity and a name we recommend investors own in the current environment, given no major generic or biosimilar risks like some of its peers."
Yee argued too that the VX-659 regimen's efficacy in heterozygous patients "creates a huge barrier to entry" for competing therapies. Combined with the "pristine safety profile" seen in earlier testing, the regimen underscores how Vertex is years ahead of rival drugmakers looking to develop their own triplets, Yee wrote.
Jefferies predicts that a successful triplet could triple or quadruple Vertex's earnings power over the next five years.
Vertex is keeping safety and additional efficacy results from the VX-659 trials under wraps until the back half of 2019 to protect data integrity. It's doing the same for the VX-445 studies, though initial data are expected in the first quarter.
Across both VX-659 trials, Vertex said the regimen was generally well tolerated and supportive of a potential New Drug Application submission.
Shares of the biotech were up less than 1% at Tuesday's market open, but rose to about $175 apiece in late morning trading — representing a more than 4% increase from Monday.