Galapagos' osteoarthritis drug flunks phase 2, dashing hopes of $250M Gilead deal

Galapagos and Servier’s GLPG1972 has failed to improve outcomes in knee osteoarthritis patients in a phase 2 clinical trial. The failure of the ADAMTS-5 inhibitor is a setback for Galapagos’ efforts to expand its opportunities beyond its faltering JAK1 inhibitor filgotinib.

Servier teamed up with Galapagos to develop new osteoarthritis therapies in 2010, going on to land the ex-U.S. rights to GLPG1972 in 2017. The partners focused on ADAMTS-5 in light of evidence that increases in the activity of the aggrecanase trigger osteoarthritis by driving cartilage aggrecan loss. In preclinical work, GLPG1972, also known as S201086, showed chondroprotective effects, leading the partners to move into the clinic and persuading Gilead Sciences to secure an option on the U.S. rights. 

Gilead can exercise its $250 million option upon the completion of the phase 2 ROCCELLA trial. With top-line data from the study now available, there is little evidence to suggest that Gilead will take up its option or that GLPG1972 has a future at any company. In describing the data, Galapagos and Servier said “no signal of activity was observed in the topline results.” 

The primary endpoint looked at changes in cartilage thickness from baseline to Week 52 in patients on placebo compared to that of their peers who received one of three doses of GLPG1972. Cartilage thickness reduced by 0.116 mm in placebo patients over the course of the clinical trial. The smallest reduction, 0.068 mm, was seen in the low-dose group, but that fell short of statistical significance.

With the medium and high doses performing comparably to placebo, with reductions of 0.097 mm and 0.085 mm, respectively, the primary endpoint data is largely devoid of positive signs. The bleak picture was completed by the failure of GLPG1972 to beat placebo against secondary endpoints, including some that looked at clinical outcomes.

Going into 2020, the anticipated GLPG1972 readout was a footnote for Galapagos in a year set to be dominated by efforts to bring Gilead-partnered JAK1 inhibitor filgotinib to market. However, with the FDA issuing a complete response letter to filgotinib, at best delaying entry to a competitive market, the focus on Galapagos’ other pipeline prospects has increased.   

“We had always viewed the trial as high risk but note the failure is a further blow to sentiment after the filgotinib U.S. FDA rejection in August, which has also led to heightened scrutiny on upcoming pipeline readouts,” analysts at Jefferies wrote in a note to investors.

The ROCCELLA readout is the first of a series of data drops that will show whether Galapagos has a pipeline capable of offsetting diminished expectations for filgotinib. Later this year, Galapagos is set to share phase 2a data on GLPG1205 in idiopathic pulmonary fibrosis (IPF). An interim analysis of a phase 3 trial of ziritaxestat in IPF is scheduled for next year. With Gilead paying $5 billion upfront to secure broad access to Galapagos’ pipeline, the data have implications beyond the Belgian biotech.