AbbVie has dumped one of Galapagos’ cystic fibrosis regimens after getting a look at underwhelming clinical data on a component of the triple combination. The action prompted Galapagos to review the future of its relationship with AbbVie—and provided a boost to cystic fibrosis rival Vertex.
Galapagos has moved one AbbVie-partnered triple combination into clinical development but hopes are higher for the follow-up regimen, which features a potentiator with a shorter metabolite half-life. Despite that, AbbVie has decided against proceeding with the second, more-promising combination after reviewing data on the C2 corrector, GLPG2737, that features in both regimens.
Investigators enrolled 22 cystic fibrosis patients who were homozygous for Class II F508del mutation and on stable treatment with Vertex’s Orkambi. Two-thirds of participants received GLPG2737 on top of Orkambi, while the rest received placebo plus Vertex’s drug.
The trial met its primary, sweat chloride concentration endpoint but failed against a measure of lung function. Notably, the percentage change in the ppFEV1 measure of lung function—3.4%—came in below the 5% targeted by analysts and well under the 7% to 13% improvements achieved by Vertex’s triple combinations. Using a higher dose of GLPG2737 and pairing it with Galapagos’ drugs, not Orkambi, could give the triple combinations better efficacy but for now Vertex looks to have an edge.
Vertex’s combinations are further down the pipeline, too, meaning Galapagos faces the prospect of trying to come from behind with what may prove to be a less efficacious therapy.
“The key is Vertex sees robust and rapid effects with all of their combos and is already well into phase 3 with at least two—and Galapagos has not put out much triple data thus far,” Jefferies analyst Michael Yee wrote in a note to investors.
Galapagos may have to tackle the challenge without AbbVie. For now, AbbVie remains partnered on the first triple combination. But Galapagos is reviewing the broader cystic fibrosis partnership in light of AbbVie’s decision to drop the second triple combination.
AbbVie’s decision further complicates one of the more fractious partnerships in biotech. Three years ago, AbbVie dumped Galapagos’ JAK inhibitor filgotinib and switched focus to its rival drug, leaving its one-time partner trailing in the race to market. The existing cystic fibrosis partnership continued but there have been signs of tension. According to Dutch newspaper Het Financieele Dagblad, Galapagos CEO Onno van de Stolpe thinks AbbVie is to blame for delays to the cystic fibrosis program and that it would advance just as well without the Big Pharma.
Galapagos may now get a chance to find out whether van de Stolpe is right.