Spyre Therapeutics reported mixed Phase 2 results for its experimental drug SPY072 in rheumatoid arthritis, with efficacy endpoints meeting nominal significance but falling short of the company’s internal thresholds for monotherapy development.
The RA sub-study of the Phase 2 SKYWAY basket trial enrolled 143 patients with moderate to severely active disease who had insufficient response to prior therapies. At week 12, the primary endpoint—a change from baseline in DAS28-CRP—showed a -1.9 improvement for the low-dose SPY072 group and a -1.5 improvement for the high-dose group, compared with a -1.3 change in the placebo arm. Secondary and exploratory endpoints also demonstrated nominally significant benefits, with the high-dose group achieving a 63% ACR20 response and the low-dose group reaching 58%, versus 43% for placebo. ACR50 responses were 38% for the low dose, 31% for the high dose, and 19% for placebo.
Safety outcomes were favorable, with adverse events reported in 27% of treated patients versus 36% in the placebo group. Most events were mild to moderate, and no drug-related serious adverse events were recorded. One death occurred in the placebo arm.
Despite the positive signal, Spyre stated the effect size did not meet its criteria to advance SPY072 as a monotherapy in rheumatoid arthritis. The company will instead focus on combination approaches and other indications. Topline data for psoriatic arthritis and axial spondyloarthritis are still expected in the fourth quarter of 2026, while results for SPY072 combined with IL-17A/F in hidradenitis suppurativa are anticipated between late 2027 and early 2028.
