Oral Anti-TNF Agent Met Key Efficacy Endpoints in Phase 2 Clinical Trial

This week, Israel-based Protalix BioTherapeutics, Inc, announced positive results from a phase 2 clinical trial for its orally administered anti—tumor necrosis factor (anti-TNF) drug, OPRX-106, a plant cell–expressed recombinant human TNF receptor II fused to an IgG1 Fc domain.

Protalix says that OPRX-106 met its key efficacy endpoints in the open-label, 2-arm study of OPRX-106 in 24 patients with mild to moderate ulcerative colitis (UC). Among the patients, who were randomized to receive oral administration of either 2 mg or 8 mg of the study drug once daily for 8 weeks, 67% experienced a clinical response and 28% achieved clinical remission.

Other key efficacy endpoints were also met, with 72% of patients showing improvement in rectal bleeding scores, 72% of patients demonstrating an improvement in fecal calprotectin, and 61% of patients showing an improved Gebos score (a histopathological scoring for the assessment of disease activity in UC).

At week 8, improved Mayo scores were observed in 89% of patients, with an average decrease in Mayo score of 45%—or 3 points—from baseline. No anti-drug antibodies were detected, and Protalix says that only mild to moderate adverse events were reported, with headaches being the most common.

“We are very excited by these results,” said Moshe Manor, president and CEO of Protalix. “They demonstrate efficacy and a lack of immunogenicity together with a favorable safety profile, which could potentially overcome one of the most challenging drawbacks of current ulcerative colitis therapies administered via injection and infusion.”

In January 2018, the company reported positive interim data from the first 14 patients to complete 8 weeks of treatment. The interim data demonstrated that 57% of patients achieved clinical response at week 8 and 36% achieved clinical remission.

Protalix is not the first to attempt to deliver anti-TNF therapy in an oral administration; in 2016, Avaxia Biologics reported positive results of a first-in-human trial of its AVX-470, a polyclonal bovine-derived anti-TNF drug, in patients with UC, saying that the agent was safe and well tolerated in the trial. However, Circle33 LLC, which later acquired Avaxia’s patents for the drug, has not reported any further developments.