Protalix Announces Positive Phase 2 Clinical Data for Oral Anti-TNF Agent

On January 2, Israel-based Protalix BioTheraprutics announced positive interim data from its phase 2 clinical trial of a proposed oral anti—tumor necrosis factor (anti-TNF) therapy, OPRX-106.

The randomized, open-label, 2-arm study of the drug was conducted in patients with mildly or moderately active ulcerative colitis (UC). A total of 24 patients were randomized to receive 2 mg or 8 mg of OPRX-106, administered orally, once daily for 8 weeks. The first 14 patients have completed the study, and 4 patients are currently in treatment and follow up. The key efficacy endpoints included clinical response and remission utilizing the Mayo score. Safety and pharmacokinetics were also evaluated.

The interim data demonstrate that 57% of patients achieved clinical response at week 8, and 36% achieved clinical remission. In the rectal bleeding analysis, a sub-category of the Mayo score, 79% of patients showed improvement; 86% of patients achieved an improvement in calprotectin levels; and 64% had improvement in terms of Geboes score, a measure of disease activity in UC.

Protalix reports that its proposed anti-TNF is a plant cell-expressed recombinant human TNF receptor II fused to an IgG1 Fc domain, and that “the plant cells function as a natural delivery vehicle, having the unique attribute of a cellulose cell wall which makes them resistant to degradation compared to proteins produced via mammalian cell expression” while passing through the digestive tract after oral administration.

If eventually approved, OPRX-106 could prove to be a strong competitor to existing anti-TNF innovator and biosimilar products for a share of the UC marketplace. Professor Yaron Ilan, chairman of the Department of Medicine at The Hadassah Hebrew University Medical Center in Jerusalem, said that proposed drug has “the potential benefit of significantly lower side effects as it does not suppress the immune system while redirecting it in an anti-inflammatory direction, as opposed to the currently approved anti-TNF treatments, all of which are administered via injection or infusion, and carry potential short and long-term side effects.”

Other drug developers have sought to develop novel, orally administered anti-TNF agents as well; in 2016, Avaxia Biologics reported positive results of a first-in-human trial of its AVX-470, a polyclonal bovine-derived anti-TNF agent, in patients with UC. However, Circle33 LLC, which subsequently acquired the patents for the investigational drug from Avaxia, has not reported any further developments in its clinical program for AVX-470.