Phase 2 Trial of PRA023 in SSc-ILD Patients Planned for Next Year

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by Marisa Wexler MS |

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Prometheus Biosciences is planning a clinical trial of its investigational anti-inflammatory and antifibrotic medication PRA023 in people with systemic scleroderma-associated interstitial lung disease (SSc-ILD), a form of scleroderma characterized by inflammation and scarring (fibrosis) in the lungs.

The Phase 2 study, called ATHENA-SSc-ILD, is planned to launch early next year. The U.S. Food and Drug Administration (FDA) has already given clearance for the trial, which aims to enroll about 100 patients who will be randomly assigned to either PRA023 or a placebo, Prometheus reported in a press release.

The trial’s main goal is to assess the impact of treatment on forced vital capacity (FVC), a measure of lung function based on how much air a person can exhale forcibly after a deep breath, at 50 weeks (nearly a year) of treatment. Other measures of lung damage and scleroderma severity will also be assessed.

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PRA023 is an antibody therapy designed to bind to TL1A (tumor necrosis factor-like cytokine 1A), which is a signaling protein that promotes inflammation and fibrosis. Notably, the investigational medicine is designed to bind to both active and inactive forms of TL1A.

“PRA023’s therapeutic target, TL1A, has been shown to mediate both inflammation and — critical to our interest in SSc-ILD — fibrosis,” James R. Seibold, MD, clinical lead of the SSc-ILD program at Prometheus, said in the release.

“In the last several years, numerous papers have been published linking TL1A to pulmonary fibrosis [lung scarring]. Therefore, we believe that PRA023 offers significant promises for the treatment of this devastating disorder,” Seibold added. “Importantly, currently available therapeutics have had mixed results in clinical trials and do not appear to have robust impact on patient quality of life.”

PRA023 is currently being evaluated in Phase 2 trials in Crohn’s disease (NCT05013905) and ulcerative colitis (NCT04996797), two forms of inflammatory bowel disease.

Top-line data from these studies, both still enrolling, are expected in late 2022, the company reported.

Prometheus also announced positive data from a Phase 1 trial (NCT04676178) that tested PRA023 in healthy volunteers. The study enrolled 69 people — some were given a single dose of the therapy and followed for 14 weeks, others were given multiple doses and followed for 18 weeks.

Results showed that the medication was well-tolerated, with no safety signals reported. There also were no adverse reactions to the infusion used to administer PRA023, or drug-related extensions in infusion time at doses up to 1000 mg delivered over the course of half an hour.

Fewer than 20% of participants given a therapeutically relevant dose (either one dose of 1,000 mg, or multiple 200 to 500 mg doses) developed an immune response against the investigational therapy. Such immune responses may result in side effects or lessen the efficacy of medicines. According to Prometheus, immune responses in the study had no noteworthy impact on PRA023’s safety or its pharmacology measures.

Phase 1 data also indicated that PRA023 bound robustly to its target, TLA1, the company reported. Based on estimations, the therapy bound its target more than four times as strongly as it would have if it only targeted the active form of the protein.

“PRA023’s ability to potently bind and neutralize both the active and inactive forms of TL1A may lead to highly effective inhibition of TL1A,” said Allison Luo, chief medical officer of Prometheus.

Added Mark McKenna, CEO and chairman of Prometheus, “we strongly believe that PRA023 has the potential to be a best-in-class TL1A inhibitor to address immune-mediated diseases.”