Spyre Therapeutics reported mixed results from the Phase 2 SKYWAY trial of its experimental drug SPY072 in rheumatoid arthritis, with efficacy metrics falling short of the company’s internal prioritization threshold for monotherapy development.
The trial enrolled 143 patients with moderately to severely active rheumatoid arthritis who had shown inadequate responses to conventional or advanced therapies. At the 12-week mark, the primary endpoint—change from baseline in DAS28-CRP—showed a statistically significant benefit in the low-dose group, with a reduction of 1.9 compared to 1.5 in the high-dose group and 1.3 in the placebo group.
Secondary and exploratory endpoints provided additional context. The ACR20 response rate reached 63% in the high-dose group versus 58% in the low-dose group and 43% in the placebo group, with the high dose showing a nominally significant improvement. For ACR50, the low-dose group reported a 38% response rate, outperforming the high-dose (31%) and placebo (19%) groups.
Safety data indicated the drug was generally well-tolerated, with adverse events reported in 27% of participants receiving SPY072 compared to 36% in the placebo group. Most events were mild to moderate in severity, and no serious adverse events were deemed related to the treatment. One death occurred in the placebo arm.
Despite the positive signals in some endpoints, Spyre stated the overall efficacy did not meet its internal threshold to advance SPY072 as a monotherapy for rheumatoid arthritis. The company plans to present preliminary data for psoriatic arthritis and axial spondyloarthritis in the fourth quarter of 2026, with combined SPY072 and IL-17A/F data for hidradenitis suppurativa expected in late 2027 or early 2028.
