Spyre deprioritises arthritis drug after Phase 2 results

Spyre Therapeutics’ hopes for its anti-TL1A antibody SPY072 in rheumatoid arthritis (RA) have hit a bump in the road after phase 2 data fell short of the company’s target for prioritising the drug as a monotherapy.

Expectations for the drug were high, however, results released by the company revealed that, while SPY072 did show statistically significant benefits on some measures of disease activity, the effect was not significant enough to meet Spyre’s internal threshold for taking the programme forwards in RA.

In the phase 2 SKYWAY-RA study, patients with moderate to severe rheumatoid arthritis received one of two doses of SPY072 or placebo. The primary endpoint was change from baseline in the Disease Activity Score in 28 joints using C-reactive protein (DAS28-CRP), while ACR20 response at week 12 was a key secondary endpoint.

Topline results showed that, after 12 weeks, the Disease Activity Score in 28 joints using C-reactive protein, or DAS28-CRP, had fallen by 1.5 points in the higher-dose group and 1.9 points in the lower-dose group. The placebo group recorded a 1.3-point reduction.

The resulting placebo-adjusted improvements were 0.2 and 0.6 points, respectively. Only the lower dose achieved statistical significance on the DAS28-CRP measure.

Spyre had previously set a target of roughly a one-point placebo-adjusted reduction in DAS28-CRP for patients whose disease had failed to respond to TNF inhibitors.

“The SKYWAY trial was designed to explore the safety and efficacy of TL1A inhibition in a range of rheumatic diseases to identify opportunities for indication-leading products. The results today do not lead us to prioritise SPY072 as a monotherapy in RA. However, the favourable safety profile of TL1A inhibition alongside demonstrated efficacy across inflammatory bowel disease, HS, and now RA provide increased conviction that our long-acting TL1A antibodies have potential in a range of autoimmune diseases and as optimal combination components,” said Cameron Turtle, DPhil, CEO at Spyre.

The antibody did perform better on some of the study’s other measures. Spyre said both doses produced statistically significant benefits on one or more of the primary, key secondary, and exploratory endpoints, including ACR20 and ACR50 responses.

The treatment was also generally well tolerated, with adverse events reported in 27% of people receiving SPY072 and 36% of those given placebo, with most described as mild or moderate.

In a statement, Spyre said the findings provide proof of mechanism for TL1A inhibition in RA and support continued investigation of the target in other autoimmune diseases.