Spyre Therapeutics reported mixed Phase 2 results for its experimental drug SPY072 in a rheumatoid arthritis sub-study, with the low-dose arm outperforming placebo but the high-dose arm falling short of expectations.
The study evaluated 143 patients with moderate to severely active rheumatoid arthritis who had insufficient responses to prior therapies. At 12 weeks, the primary endpoint—a reduction in DAS28-CRP scores—showed a statistically significant improvement in the low-dose group (-1.9) compared to placebo (-1.3). The high-dose group recorded a change of -1.5, which did not meet statistical significance.
Secondary and exploratory endpoints provided additional nuance. The high-dose arm achieved a 63% ACR20 response rate versus 43% for placebo, a nominally significant improvement, while the low-dose group reached 58%. For ACR50, the low-dose arm outperformed placebo (38% vs. 19%), whereas the high-dose arm recorded 31%.
Safety outcomes were broadly favorable, with adverse events reported in 27% of treated patients compared to 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 mixed efficacy signals, Spyre opted not to prioritize SPY072 as a monotherapy for rheumatoid arthritis based on its internal benchmarks. The company plans to advance psoriatic arthritis and axial spondyloarthritis trials, with topline data expected in the fourth quarter of 2026. Data for hidradenitis suppurativa, in combination with IL-17A/F, is anticipated in late 2027 or early 2028.
Shares of Spyre closed at $107.36 on August 25, up 0.67%, before dropping 17.04% in after-hours trading.
