aTyr's Efzofitimod Fails to Meet Primary Endpoint in Phase 3 Pulmonary Sarcoidosis Trial

aTyr Pharma's phase 3 trial of efzofitimod for the treatment of moderate-to-severe pulmonary sarcoidosis has failed to meet its primary endpoint, dealing a significant blow to the company's prospects in the multibillion-dollar inflammatory lung disease market. Despite the setback, aTyr remains optimistic and plans to engage in discussions with the FDA regarding potential paths forward.

Trial Results and Implications

The phase 3 trial, which aimed to position efzofitimod as a steroid-sparing agent, compared the effect of 48 weeks of dosing with efzofitimod against placebo on mean daily oral corticosteroid (OCS) dose. Results showed that efzofitimod performed no better than placebo in reducing OCS dose, with the high dose of efzofitimod achieving an average reduction to 2.79 mg compared to 3.52 mg for placebo.

Dr. Sanjay Shukla, CEO of aTyr, attributed the failure to an unexpectedly high placebo response rate. "We assumed that patients on efzofitimod would taper from baseline to an average daily prednisone dose between 1 to 4 milligrams, with placebo expected to taper to between 4 to 7," Shukla explained. "The drug performed accordingly to what we projected. However, we did not achieve statistical significance as the placebo tapering outperformed even our most aggressive modeling."

Secondary Endpoints and Future Prospects

Despite missing the primary endpoint, aTyr highlighted several positive secondary outcomes from the trial. The company reported a clinical improvement in the KSQ-Lung patient-reported measure of health-related quality of life, with a 10.36-point change on the high dose compared to a 6.19-point change on placebo. Additionally, a responder analysis showed that 52.6% of patients on the high dose of efzofitimod achieved complete steroid withdrawal, compared to 40.2% on placebo.

Shukla remains optimistic about efzofitimod's potential, stating that the study demonstrated patients with chronic symptomatic sarcoidosis "can be managed with substantially lower steroid doses than previously thought without the fear of worsening disease." He also emphasized that treatment with efzofitimod was associated with greater steroid reduction, including steroid withdrawal, clinical improvement in quality of life, and maintenance of lung function.

Market Response and Next Steps

The news of the trial failure had an immediate and significant impact on aTyr's stock, which fell 80% to $1.21 in premarket trading. Despite this setback, the company plans to engage in discussions with the FDA about potential paths forward. Shukla expressed confidence that the FDA will be "a collaborative partner" given the lack of effective therapies in pulmonary sarcoidosis.

As aTyr navigates this challenging period, the broader pharmaceutical industry will be watching closely to see how regulators respond to the mixed results and whether there remains a viable path forward for efzofitimod in the treatment of pulmonary sarcoidosis.