- Vertex Pharmaceuticals' position as the leading company in the market for treatments of cystic fibrosis became a little more secure Friday, when competitor Galapagos reported data from a small proof-of-concept trial that analysts dismissed as "disappointing" and "underwhelming."
- The study, which enrolled just 22 patients, evaluated the addition of Galapagos' experimental C2 corrector on top of Vertex's approved doublet Orkambi in cystic fibrosis patients homozygous for a mutation known as F508del.
- While data showed the triple combination led to a positive trend on a measure of lung function, the change from baseline was not statistically different from placebo and fell well short of increases demonstrated by novel triple combinations developed by Vertex.
In cystic fibrosis drug development, the bar for success is not just a study's goal, but often how well clinical results measure up to data from Vertex.
Galapagos' study actually met its primary endpoint, showing the addition of the biotech's experimental C2 corrector to Orkambi (lumacaftor/ivacaftor) significantly reduced sweat chloride concentration compared to placebo.
The drug's safety profile looked clean, as well, with Galapagos reporting only no apparent difference in adverse events between treatment and placebo.
But the experimental triple combination fell short of statistical significance on the average change from baseline in forced expiratory volume (FEV1), a measure of lung function. The numerically superior 3.4% increase brought on by the combination also is substantially lower than the 7% to 13% increases reported by Vertex for its own novel triple combos.
"The result is even lower than the mid to high single digit incremental FEV1 effect we had anticipated, and raises questions about the viability of this molecule, and [Galapagos'] overall development strategy in [cystic fibrosis]," wrote Leerink analyst Geoffrey Porges in a June 29 note to investors.
Vertex has already moved two triple combos into Phase 3 testing and recently secured an approval of a new doublet called Symdeko (tezacaftor/ivacaftor) that could help further boost its clinical development plans.
Galapagos does have one, different triple combo in clinical testing, with interim results expected in the third quarter. The study, called FALCON, tests the same experimental C2 corrector with an investigational potentiator and C1 corrector.
AbbVie, however, has decided to back out of a triple combo study that analysts had expected to be the desired option for the companies.
"This comes as a surprise, as this has been viewed as the preferred triple since potentiator ‘2451 [used in FALCON] has a long metabolite half-life," said Jefferies analyst Peter Welford in a June 29 note.
As a result of AbbVie's decision, Galapagos said it is reviewing the future of the partnership in cystic fibrosis.
Shares in Galapagos fell by as much as 6.6% Friday morning, before gaining back some of those losses to close down just under 4%. Vertex stock, on the other hand, jumped by 15% on the news.
The increase for Vertex builds on recent gains from a setback of another potential rival, Proteostasis Therapeutics, in a Phase 1 study of its own triple combo.
In both cases of Proteostasis and Galapagos, investors hoped to see evidence the smaller biotechs' triple combo candidates could compete with the ones Vertex is taking into the clinic. Vertex has come out of both comparisons looking stronger.