Positive Phase 1 Trial Results for Systemic Sclerosis-Associated Interstitial Lung Disease Treatment

Prometheus Biosciences Inc. has just announced positive results from their Phase 1 investigation for a new treatment for systemic sclerosis-associated interstitial lung disease (SSC-ILD). This trial investigated PRA023, an anti-TL1A antibody, in healthy individuals. The company plans to initiate a Phase 2 trial of the therapy within the first part of 2022.

Systemic Sclerosis

Systemic sclerosis (SSc) is a rare disease which causes chronic immune activation and inflammation. Patients face progressive fibrosis of both their skin and their organs.

Fibrosis of the lungs is the primary cause of mortality and morbidity. This presentation of the condition is called SSc-ILD. Once the lungs are impacted, the condition is irreversible. Therapies for SSc-ILD focus on slowing down how fast the condition progresses.


PRA023 is an IgG1 mAb. It works by binding to TL1A, a tumor necrosis factor, in its active and inactive form. For patients with inflammatory bowel disease (ulcerative colitis or Crohn’s disease) who have a high TL1A expression, this therapy could drastically improve outcomes. There is an ongoing Phase 2 trial for this therapy in individuals diagnosed with ulcerative colitis as well as a Phase 2a trial for those diagnosed with Crohn’s disease.

Now, the treatment is also being developed for SSc-ILD.

The Study

This study was a placebo-controlled and double-blind investigation. It included 69 participants who were divided into nine cohorts. Six cohorts were a part of a single ascending dose phase (14 weeks at 1,000 mg) while the last three were in a multiple ascending dose phase (18 weeks at 200 mg to 500 mg).

The primary outcome examined was safety/tolerability. One of the most important secondary outcomes was the rate of immunogenicity.

PRA023 was found to be well tolerated by patients and there weren’t any safety issues reported. This includes no infusion related reactions as well as no drug-related increase in the infusion time. These results remained the same for various doses, up to 1,000mg over a 30 minute infusion.

Around 20% of all patients, across all cohorts, developed anti-drug antibodies throughout the follow up period. Additionally, immunogenicity wasn’t found to have any safety concerns, impact on pharmacokinetic parameters, or pharmacodynamic parameters.

PRA023 was found to demonstrate a robust target engagement. TL1A target coverage was improved because of the therapies ability to bind to the active and the inactive forms (approximately 4 folds higher). Inflammation and fibrosis were both mediated.

Researchers believe that this therapy could become the best-in-class inhibitor for TL1A in many immune-mediated conditions.

This new therapy could be the first to have a robust impact for patients and drastically improve quality of life.

Phase 2 Trial

A Phase 2 trial for SSc-ILD called ATHENA-SSc will be initiated soon. The plan is to enroll 100 participants. 50 will receive the placebo and 50 will receive the PRA023 treatment.

The primary endpoint of this investigation will be forced vital capacity change at the 50 week mark. Other things which will be evaluated include change in the quantitative ILD and improvement in the ACR-CRISS response score.

PRA023 has already received FDA clearance for their Investigational New Drug Application. The goal is to initiate this new Phase 2 trial within the first quarter of 2022.

You can read more about this therapy and the upcoming investigation here.

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