Galapagos, Gilead include high dose in PhIII RA trial after talk with FDA

Lab work

Galapagos ($GLPG) and Gilead ($GILD) have confirmed that their upcoming Phase III rheumatoid arthritis trial will give 200-mg doses of JAK1 inhibitor filgotinib, putting to bed concerns that a link to testicular toxicity would force the partners to limit the amount of the drug administered in the study.

When the Phase III trial gets underway in the third quarter of this year, it will include arms that give 100-mg and 200-mg daily doses to both men and women. Galapagos and Gilead confirmed the trial design following the completion of an end-of-Phase II meeting with FDA, in which they successfully allayed concerns about the potential for the higher dose of filgotinib to cause testicular toxicity. The trial will nonetheless include a dedicated male patient testicular safety study that, if positive, would generate data to quash concerns that could limit uptake of filgotinib should it come to market.

Hitting upon the trial design positions the partners to further their ambition to bring 200-mg doses to a wide range of patients. “The FINCH program, led by our collaboration partner Gilead, will enable a comprehensive Phase III evaluation of simultaneously 100 mg and 200 mg filgotinib in both males and females in major RA patient populations worldwide,” Galapagos CSO Piet Wigerinck said in a statement. “Gilead and Galapagos have worked diligently to complete the transition, such that Gilead is now poised to initiate multiple studies with filgotinib in inflammatory diseases.”

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The testicular toxicity question has hung over Galapagos since it was designing the Phase II DARWIN clinical trial program, at which time concerns raised by the FDA prompted the Belgian biotech to limit the maximum daily dose at U.S. clinical trial sites to 100 mg. The FDA flagged up concerns about the 200-mg dose on the basis of preclinical tests that showed filgotinib affected the production of sperm cells. In response, Galapagos did further preclinical tests and monitored male patients in its clinical trials, but questions about the issue still intensified after AbbVie ($ABBV) walked away from the drug.

Now, 8 months after AbbVie jilted Galapagos, the Belgian biotech has emerged from regulatory meetings with a trial design that validates its long-standing position that testicular toxicity will not be an impediment to the advance of filgotinib. That advance extends beyond rheumatoid arthritis. With the JAK1 inhibitor barreling toward the start of the FINCH clinical trial, Gilead and Galapagos are also ramping up preparations for Phase III and Phase II/III studies in Crohn’s disease and ulcerative colitis, respectively. Gilead expects to get the trials underway in the third quarter, pending regulatory talks.

- read the release (PDF)