Vertex Pharmaceuticals has set the stage for an ambitious Phase III program for its combo approach matching the experimental VX-809 and Kalydeco for cystic fibrosis. And if it can stick with the plan, Vertex ($VRTX) will cut a short path directly to an approval for the groundbreaking combo.
Already tapped by the FDA as two of its first drugs to win the agency's coveted "breakthrough" status--aimed at speeding development of truly innovative medicines--the Cambridge, MA-based developer says it is prepping a pair of late-stage studies that will enroll 1,000 patients age 12 and older in 200 sites to test two doses over 24 weeks. Patients will have two copies of the F508del mutation in the CFTR gene. And it's also planning a safety and pharmacokinetics study for a group of 6 to 11-year-olds to be used for registration in the U.S. and food for discussion with European regulators.
"This Phase III development program is a significant advance in our efforts to develop new medicines that treat the underlying cause of cystic fibrosis for people with the most common type of the disease," said Robert Kauffman, the chief medical officer at Vertex. "Importantly, these studies will evaluate two doses of VX-809 in combination with ivacaftor (Kalydeco) for 24 weeks, and pending data, enable submissions to U.S. and European regulatory authorities. People with CF are in urgent need of new treatments, and we are committed to advancing this combination through Phase III development as quickly as possible."
The 809/Kalydeco combo includes all the features that the FDA loves to see, with Vertex building on its successful work with Kalydeco to vastly expand its reach. Patients on Kalydeco and a 600 mg dose of VX-809 demonstrated a 3.4% improvement in lung function over baseline in a Phase II study that read out last fall, while patients in the placebo arm experienced a 3.3% drop through the 8th week. Analysts also speculated that a higher dose could improve that modest though significant performance. In the upcoming study Vertex investigators will test a 600 mg QD dose as well as 400 mg twice a day.
The CF program is crucial for Vertex, which developed a breakthrough hepatitis C therapy only to see sales begin to shrivel as next-gen, interferon-free programs journey through late-stage studies.
In a statement, ISI Group analyst Mark Schoenebaum quickly zeroed in on two key reveals in Tuesday's release: "Phase III design includes the higher dose of 400mg twice per day and (2) new data from the phase II cohort on this dose (looks generally similar to 600mg once a day). Overall, we are pleased that the data provided seem to indicate the higher dose has similar activity to the 600mg dose (our opinion will be controversial, however, for reasons seen below). At the very least, a worst-case scenario of 'no activity' has clearly been avoided--some Street observers worried about this since VRTX has had the data in house for several weeks and elected not to disclose (until now). Our best guess is stock is flattish on this as Street awaits the 'all-important' 661+Kalydeco data later this half. If the phase 3 is ultimately successful (late 2013/early 2014), upside for this stock could exceed anything in our coverage universe. But, with that upside risk comes downside risk as well. We remain Buy rated on Vertex, but admit it's quite binary and not for everyone."
- here's the release