- Galapagos NV on Tuesday updated investors about the progress of its cystic fibrosis pipeline. Yet the news failed to impress some analysts, who noted the company still faces a steep uphill battle before it can feasibly take on leaders in the therapeutic area.
- Among the updates were positive topline results from the FLAMINGO study, which tested four doses of Galapagos' drug GLPG2222 in cystic fibrosis patients with two copies of the F508del mutation. Early data showed a significant dose-dependent decrease in sweat chloride concentration for patients in the experimental arms compared to those receiving placebo.
- Galapagos also initiated a Phase 1 study of its backup novel C1 corrector, GLPG2851, resulting in a $10 million milestone payment from its development partner AbbVie Inc. A trial investigating Galapagos' first triple combination treatment for cystic fibrosis will begin dosing in the first quarter of 2018, with interim data slated to come out mid-way through the year. Additionally, Galapagos has dosed the first patients in a Phase 2 study of GLPG2737, a C2 corrector, paired with Vertex Pharmaceutical Inc.'s Orkambi and a Phase 1 study of its second triple combo therapy.
Vertex stands alone at the top when it comes to cystic fibrosis treatments, making it difficult for less advanced players like Galapagos to make waves in the market.
Kalydeco (ivacaftor) and Orkambi (lumacaftor/ivacaftor) are already earning more than half a billion dollars per quarter for Vertex, and a third product may be right around the corner. The Food and Drug Administration will likely approve a Kalydeco/tezacaftor doublet early this year, which can then pave the way the big biotech's triple combo investigations.
"[G]eneral FDA requirements stipulate that combination triple pills need to show that they are better than doubles, and that doubles are better than singles," Jefferies analyst Michael Yee wrote in a Jan. 2 investor note on Vertex, adding that if the Kalydeco/tezacaftor gains approval, the biotech will be able to easily do head-to-head studies pitting the doublet against a triple combination.
"Bottom line, [Vertex] could announce shortly a very fast timeline for its Phase 3 triple program, and the company is well ahead of its competitors which are still in early proof of concept stages."
That isn't to say Vertex's success takes away from Galapagos'. In fact, the Belgium-based company has seen its stock steadily rise over the last year amid business and pipeline victories.
But the strong efficacy and safety of Vertex's drugs — as well as the head start it has in bringing those drugs to market — does set a high bar to clear.
"[Vertex] bulls already know a competitor is developing a drug that might show proof of concept, and the reality is that the competitor is so far behind and faces several challenges that it becomes irrelevant for [Vertex] in both the short and longer term," Yee wrote.
Galapagos' leading cystic fibrosis drugs in the pipeline are its potentiator GLPG1837 and C1 corrector GLPG2222. The new results for the latter of those treatments, while positive, also bring about some questions.
Two of the secondary endpoints of FLAMINGO were change from baseline in sweat chloride concentration and absolute change from baseline of forced expiratory volume (FEV), which is a measure of lung function. Guggenheim Securities analyst Tony Butler contends sweat chloride isn't an endpoint that would lead to the drug's approval, meaning more information is needed on the FEV impact of GLPG2222 before it can be considered a contender to marketed drugs.
Another roadblock is FLAMINGO's design. The study enrolled just 59 patients who are part of a smaller portion of the cystic fibrosis population that is homozygous for the F508del mutation.
GLPG2222 "would compete against Orkambi, which is already on the market, or more importantly the new Orkambi — the tezacaftor/ivacaftor combination — which Vertex has already filed. This is not equivalent to the Vertex triple, which is for the heterozygous [F508] patients," Butler said.
"It's going to be really, really hard for anyone to compete, and that assumes you can get a significant population to file with regulatory agencies in the United States," he added. "I'm not sure when that's going to happen for Galapagos. I don't think there's a threat to the market today."