Efzofitimod Shows Early Signs In Helping SSc-ILD

Efzofitimod, a new drug in development by aTyr Pharma for treating interstitial lung disease (ILD), has shown early signs of clinical efficacy in those with pulmonary sarcoidosis and SSc-ILD (scleroderma-related ILD), a more severe form of the disease.

“We are excited to see early signals emerging across multiple skin assessment measures from this initial interim analysis, and we are particularly encouraged by the stable or improved modified Rodnan Skin Score (mRSS), a measure of skin fibrosis, seen in all patients,” Sanjay S. Shukla, M.D., president and CEO of aTyr Pharma, said in a statement.

This first-in-class biologic immunomodulator targets neuropilin-2 (NRP2) on activated myeloid cells to resolve inflammation without causing immune suppression.

At the 12-week point of a Phase 2 EFZO-CONNECT study, Shukla and his team of researchers observed meaningful improvement in three out of four efzofitimod-treated patients with diffuse SSc-ILD.

At the time of their assessment, researchers observed that all patients exhibited stable or improved modified Rodnan Skin Scores (mRSS). Additionally, among the four evaluable efzofitimod-treated patients with diffuse SSc-ILD, three experienced at least a 4-point improvement. It is noteworthy that the minimal clinically important difference is defined as a 4- to 6-point improvement over 12 months.

“mRSS is a sensitive clinical outcome measure, particularly for diffuse patients, so we consider this trend quite promising,” Shukla said. “As we continue enrollment and move toward the 24-week endpoints, including lung function as the primary endpoint to evaluate the ILD component of the disease, we look forward to providing additional updates upon completion of the trial.”

The randomized, double-blind, placebo-controlled, proof-of-concept study is designed to last 28 weeks and will evaluate either 270 mg or 450 mg of efzofitimod or placebo dosed intravenously monthly for a total of 6 doses in 3 parallel cohorts randomized 2:2:1, respectively.

Shukla explained that the study is designed to assess the efficacy of multiple doses of intravenous efzofitimod in improving pulmonary, cutaneous, and systemic manifestations in patients with SSc-ILD. Additionally, safety and tolerability are being evaluated as secondary outcomes.

During their study, investigators also noted preliminary indications of improvement in inflammatory biomarkers such as interferon gamma (IFN-γ) and monocyte chemoattractant protein-1 (MCP-1), as well as disease biomarkers including Krebs von den Lungen-6 (KL-6) and surfactant protein-D (SP-D).

When it came to safety, efzofitimod was generally well tolerated across all dose levels, with no treatment-related serious adverse events reported.

When complete, the study will have included 25 participants eligible to participate in a 24-week open-label extension. Efzofitimod is also currently being evaluated in the global Phase 3 EFZO-FIT study in patients with pulmonary sarcoidosis.