Efzofitimod Phase 2 study for SSc-ILD planned to launch in 2023 

FDA has cleared an investigational new drug application by aTyr Pharma

Margarida Maia, PhD avatar

by Margarida Maia, PhD |

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aTyr Pharma plans to test efzofitimod, its lead candidate for treating interstitial lung disease (ILD) associated with systemic sclerosis (SSc), in a Phase 2 clinical study this year in the U.S.

The plans come after the U.S. Food and Drug Administration (FDA) cleared an investigational new drug (IND) application to start the study, the company announced in a press release.

The medication was placed last year on the FDA’s fast track for its potential to become a treatment for SSc-ILD, and also received orphan drug status in the U.S.

Efzofitimod is being tested in EFZO-FIT (NCT05415137), a company-sponsored Phase 3 study for pulmonary sarcoidosis, a disease where small clumps of inflammatory cells grow in the lungs.

“We are thrilled to expand our efzofitimod clinical program to include a Phase 2 study in SSc-ILD with clearance of this IND,” said Sanjay S. Shukla, MD, aTyr’s president and CEO.

Scleroderma, or SSc, occurs when an overactive immune system causes scarring and inflammation that can affect the skin, internal organs, and blood vessels of the body.

A feature of ILD is scarring and inflammation that damages the tissue around the air sacs in the lungs. Symptoms include shortness of breath, a dry cough, and fatigue. Treatment involves immunosuppressants to tamp down the immune system and anti-inflammatory medications to ease inflammation. Some may require oxygen therapy to help with breathing.

“ILD is the leading cause of death in patients with scleroderma. Current treatment options may help to slow lung function decline, but do not impact underlying disease or improve quality of life,” Shukla said. “There remains a medical need for more effective and safer therapies for patients with this debilitating disease.”

Efzofitimod is designed to tune the activity of a protein called neuropilin-2 (NRP2) that can be found on the surface of certain immune cells and is believed to play a key role in inflammation. By tuning NRP2, efzofitimod would help reduce scarring and inflammation.

“The prospect of a new therapeutic target for [SSc-ILD] is welcome news for patients suffering from this disease, which has limited treatment options,” said Kristin Highland, MD, director of the Cleveland Clinic’s Rheumatic Lung Disease Program.

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Evaluating efzofitimod’s safety, efficacy, tolerability

If all goes as planned, the Phase 2 study will enroll 25 people with progressive SSc-ILD who are receiving background treatment with mycophenolate mofetil, an immunosuppressant. It will be conducted in multiple centers across the U.S.

The goal is to evaluate the effectiveness, safety, and tolerability of multiple doses of efzofitimod over 28 weeks.

Participants will be randomized to one monthly efzofitimod dose of 270 mg or 450 mg, or a placebo. They’ll receive a total of six doses, each given intravenously (into a vein).

The researchers will be watching for changes in the lungs and in the skin. A skin biopsy — where a skin sample is removed for examination in the lab — will be performed at the entry to the study (baseline) and 12 weeks later.

Shukla said “preclinical data showing efzofitimod reduces lung and skin fibrosis [scarring] in an animal model of SSc-ILD and clinical data demonstrating proof-of-concept for efzofitimod in patients with pulmonary sarcoidosis” helped inform the decision by the FDA to clear the IND application.

Proof-of-concept came from a Phase 1/2 study (NCT03824392) in people with pulmonary sarcoidosis, where efzofitimod was generally tolerated well compared with a placebo. It also was found to improve lung function and ease symptoms such as shortness of breath, cough, and fatigue.

Efzofitimod holds orphan drug designations for sarcoidosis in the U.S. and Europe.