An herbal fusion protein is safe and effective in inducing favorable immune modulation in mild to moderate patients ulcerative colitis without immune suppression: reported side effects.
OPRX-106, a recombinant TNF fusion protein that orally expresses BY2 plant cells, has been shown to be effective as an anti-TNF-alpha therapy, according to Einat Almon, PhD, of Protalix Biotherapeutics, and colleagues.
“Oral immune therapy is based on the concept of oral administration of non-absorbable compounds aimed at the intestinal immune system to redirect the systemic immune system in an anti-inflammatory direction, without immunosuppression“, the researchers said.
A phase 1 study of OPRX-106 in healthy human volunteers showed safety effects and immune modulators at doses of 2, 8, or 16 mg / day.
In this phase 2nd clinical trial published in the Journal of Clinical Gastroenterology, researchers enrolled 24 patients with ulceration colitis (11 men and 13 women) aged 23 to 73, with a mean age of 42.6 years. Patients received 2 mg or 8 mg of OPRX-106 at least once daily for 8 weeks. All patients were monitored for 6 hours after receiving medication on day 1 and week 8 for pharmacokinetic samples and a lower endoscopy was performed at week 8.
After eight weeks, 67% of patients demonstrated clinical response and 28% showed clinical remission.
Clinical response and clinical remission were defined using a specific set of criteria, including improved Mayo score. The clinical response was a “decrease in the May score of at least 3 points, a decrease in the low score for rectal bleeding of at least 1 point, [and] a subpoint of rectal bleeding of 0 or 1. “Clinical remission at week 8 was defined as” Mayo score clinically asymptomatic ≤2 without any individual score greater than 1 point after treatment, histopathological improvement in histological classification of Geboes from baseline to week 8, improvement of high-sensitivity C-reactive protein levels from baseline to week 8, improvement of fecal calprotectin levels from baseline to week 8 and changes in systemic parameters of immune modulation from baseline to week 8. “
In addition, 89% of patients experienced some degree of improvement in Mayo scores, 61% improved mucosa, and 33% achieved mucosal healing.
No side effects associated with general immune suppression were reported. The researchers said no patient discontinued the study due to adverse events. However, 40 adverse events were generally reported in 15 patients; 95% of these were mild to moderate and 40% were reported as treatment-related. There are no differences in adverse events related to the two doses.
The researchers noted that there was evidence of a systemic anti-inflammatory effect with decreased serum levels of the proinflammatory cytokines interleukin-6 and interferon-gamma that correlated with the clinical response. Similarly, an increase in the subset of CD3 + CD4 + CD25 + Foxp3 + suppressor lymphocytes was correlated with the clinical response.
The results of the study were limited by the small sample size, open design, and lack of control subjects. However, by targeting the intestinal immune system, the drug “may provide a response to long-term immune suppression found in patients with chronic disorders who use these agents for extended periods of time, in addition to response due to neutralizing antibodies, “they concluded.
The results provide the basis for further research
“Doing a study of a new treatment for ulcerative colitis is valuable and timely because the options available are limited,” Atsushi Sakuraba, MD, of the University of Chicago, said in an interview. “Currently available TNF antagonists are administered intravenously or subcutaneously and are at risk for infectious complications, so it is important to develop an agent that can be administered orally with fewer side effects.”
Although the data are preliminary, Sakuraba emphasized that the front message for doctors is that “the current open-label study consisting of a small number of subjects showed that OPRX-106 was effective and safe in active ulcerative colitis. , To confirm these findings, randomized, placebo-controlled studies with higher potency are needed.
The study was supported by Protalix Biotherapeutics; Almon and several co-authors are employed by Protalix Biotherapeutics. Sakuraba had no financial conflict to reveal.
This article originally appeared on MDedge.com, which is part of the Medscape professional network.