Spyre Drops Rheumatic Program After Trial Setbacks

Spyre Therapeutics halted SPY072 development in rheumatic diseases after sub-studies missed primary endpoints, while advancing the drug in a hidradenitis suppurativa combination trial.

Updated on Nov. 4, 2026 in Arthritis

Bold flat-color editorial illustration of a single unlabeled glass vial on a steel laboratory bench, suggesting drug development research. — Spyre Therapeutics dropped its SPY072 rheumatic-disease program after Phase 2 SKYWAY sub-studies missed primary endpoints in psoriatic arthritis and axial spondyloarthritis. AI Illustration. Upload story photo >

Spyre Therapeutics has dropped development of SPY072 in rheumatic diseases after its Phase 2 SKYWAY sub-studies failed to meet primary endpoints in psoriatic arthritis and axial spondyloarthritis. The company is instead moving the drug into a Phase 2 SKYLIGHT combination trial with bimekizumab in hidradenitis suppurativa.

Why it matters

The setbacks narrow the development path for the TL1A-targeting drug in rheumatic conditions, shifting its focus toward skin inflammation. For patients with arthritis in the United States, the decision means no near-term rheumatic treatment option from this program.

In the 143-patient RA sub-study, the low dose achieved a DAS28-CRP change of -1.9 versus -1.3 for placebo at Week 12, with adverse events in 27% of SPY072 patients versus 36% of placebo. Spyre has not disclosed response rates or effect sizes for its psoriatic arthritis or axial spondyloarthritis sub-studies.

The players

Spyre Therapeutics

Spyre Therapeutics is a clinical-stage biopharmaceutical company developing anti-TL1A therapies for immune-mediated inflammatory diseases.

The details

SPY072 is engineered with half-life extension technology for infrequent subcutaneous maintenance dosing and targets TL1A, a cytokine involved in inflammatory signaling. Spyre said the rheumatoid arthritis effect size did not meet its internal bar for prioritizing SPY072 monotherapy in RA, and the drug was well tolerated across the SKYWAY trial.

June 2026: Spyre completed enrollment in the SKYWAY RA, PsA, and axSpA sub-studies.
August 2026: RA sub-study topline results reported with a mixed readout.
September 2026: Spyre began the Phase 2 SKYLIGHT trial.
November 3, 2026: Spyre reported third-quarter results disclosing the PsA and axSpA failures.
Late 2027 or early 2028: Week 16 SKYLIGHT results for SPY072 with bimekizumab are planned.

Market Landscape

Merck reported Phase 2b success for tulisokibart in hidradenitis suppurativa in September 2026, the same month Spyre began its SKYLIGHT trial in that indication. Spyre's pivot places SPY072 in direct competition with a rival TL1A antibody for the HS market.

For people with rheumatoid arthritis, psoriatic arthritis, or axial spondyloarthritis in the United States, SPY072 will not be available as a near-term treatment option from this program. Patients currently managing these conditions should continue working with their clinicians on approved therapies.

The takeaway

Trial failures in one indication can redirect a drug's development toward another, as Spyre's move from arthritis to hidradenitis suppurativa shows. Readers following arthritis research should watch whether TL1A-targeting drugs prove effective in skin disease before expanding to joint conditions.

What happens next

Week 16 results from the Phase 2 SKYLIGHT trial of SPY072 with bimekizumab are planned for late 2027 or early 2028, and induction data from the SKYLINE ulcerative colitis trial are expected in the third quarter of 2027.