1st patient dosed in Phase 2 trial of efzofitimod for SSc-ILD
Recruiting still underway for proof-of-concept study of aTyr therapy
Dosing has begun in a Phase 2 clinical trial evaluating aTyr Pharma’s efzofitimod, a first-in-class therapy for people with interstitial lung disease (ILD) associated with systemic sclerosis (SSc) — together known as SSc-ILD.
Recruitment for the proof-of-concept EFZO-CONNECT study (NCT05892614), which aims to enroll up to 25 adult patients, is ongoing at sites in Ohio and Louisiana. Additional locations in California, Illinois, Oklahoma, South Carolina, and Texas are expected to open soon.
“We are very pleased to begin patient dosing in EFZO-CONNECT,” Sanjay S. Shukla, MD, president and CEO of aTyr, said in a company press release.
“We believe there is compelling rationale that efzofitimod has the potential to target the underlying disease pathology [development] central to this form of ILD and positively impact lung function and improve outcomes in these patients,” Shukla said.
Scleroderma, or SSc, is marked by an overactive immune system that causes inflammation and fibrosis, or scarring, that can affect the skin, organs, and blood vessels. In ILD, the tissue around the air sacs in the lungs is damaged, leading to disease symptoms such as shortness of breath, a dry cough, and fatigue.
Current treatment for SSc-ILD involves immunosuppressants to dampen immune responses and anti-inflammatory medications to ease inflammation. Some patients may need oxygen therapy to support breathing. There are, however, no therapies that address the disease’s causes.
“Patients with SSc-ILD have limited treatment options and poor prognosis, with ILD being their leading cause of death,” said Kristin Highland, MD, director of the rheumatic lung disease program at the Cleveland Clinic, in Ohio.
“This study, which evaluates a therapy that targets the inflammatory and fibrotic characteristics of this disease, is an important step forward towards developing a treatment that can potentially improve the prognosis and quality of life for patients in need,” Highland said.
Efzofitimod is designed to modulate neuropilin-2 (NRP2), a protein found at elevated levels in immune cells during inflammatory activity. As such, the therapy has the potential to reduce lung inflammation and scarring in patients with ILD.
According to Shukla, “efzofitimod has been shown preclinically to reduce lung and skin fibrosis in models of SSc, and NRP2, efzofitimod’s binding partner, is expressed in the skin of SSc patients.”
This study, which evaluates a therapy that targets the inflammatory and fibrotic characteristics of this disease, is an important step forward towards developing a treatment that can potentially improve the prognosis and quality of life for patients in need.
EFZO-CONNECT is enrolling patients with active disease or with worsened lung function during the previous year. Participants will be receiving the immunosuppressant mycophenolate mofetil or related compounds as a background regimen.
Given intravenously, or into a vein, the therapy will be administered at doses of 270 mg or 450 mg. The patients will be randomly assigned to one of the two monthly doses of efzofitimod or a placebo for a total of six doses over 28 weeks, or about six months.
The study’s objectives are the therapy’s impact on lung, skin, and systemic (bodywide) manifestations of SSc-ILD, as well as its safety and tolerability.
The medication recently received orphan drug and fast-track designations in the U.S. for its potential to treat SSc-ILD. In the European Union, it was given orphan drug status for SSc.
Efzofitimod also is being tested in EFZO-FIT (NCT05415137), an aTyr-sponsored Phase 3 study for pulmonary sarcoidosis. That condition is characterized by small clumps of inflammatory cells that form in the lungs.
In a previous Phase 1/2 trial (NCT03824392), efzofitimod was found to safely improve lung function and lessen related symptoms such as shortness of breath, cough, and fatigue in pulmonary sarcoidosis patients.
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