In 455 subjects, the eradication rate of RHB-105 was superior to that of the active comparator (83.8% vs 57.7%, p< 0.0001).
David Graham, MD
A phase 3 trial presented at the American College of Gastroenterology’s Annual Scientific Meeting (ACG 2019) in San Antonio, Texas, offers new evidence supporting a rifabutin- (RHB-105) based triple therapy for the treatment of Helicobacter pylori infection.
H pylori, a World Health Organization high-priority pathogen, has rendered previously active therapies dangerously ineffective as its antimicrobial resistance profile strengthens.
Other clinical studies of RHB-105 (an “all-in-one” fixed dose oral capsule comprising rifabutin 50 mg, amoxicillin 1000 mg, and omeprazole 40 mg) have shown its promise, and now investigators are presenting findings from a phase 3, double-blind, active comparator study (ERADICATE Hp2) of a 4-capsule regimen of RHB-105 compared with a high dose proton pump inhibitor-amoxicillin dual therapy (amoxicillin 1000 mg, omeprazole 40 mg) for the eradication of H pylori.
Study participants were randomized 1:1 to receive a treatment regimen every 8 hours for 14 days. Those who were dyspeptic, treatment-naïve subjects with confirmed H pylori infection, 13C UBT (urea breath test) and endoscopy (Campylobacter-like organism test, pathology, or culture) had 13C UBT primary end point assessed at least 4 weeks post-treatment.
Investigators monitored any subject who failed H pylori eradication for development of resistance and offered physician-directed standard-of-care.
In 455 subjects, the eradication rate of RHB-105 was superior to that of the active comparator (83.8% vs 57.7%, p< 0.0001). The study drug also demonstrated superiority over the comparator in a pre-specified pharmacokinetic population where the efficacy of RHB-105 was evaluated in subjects with positive drug levels at day 13 (90.3% vs. 64.7%, p< 0.0001).
Efficacy of the study drug was not affected by clarithromycin or metronidazole resistance, and no resistance to RHB-105 was noted pre- or post-treatment. Compliance was similar across both treatment arms, and adverse events were comparable as well, with no drug-related serious adverse events reported in either group. Diarrhea (10.1% vs 7.9%) and rash (1.3% vs 0.0) were the most common adverse events reported in the RHB-105 arm ( >1% over comparator). In patients who failed double-blinded therapy, the physician-directed standard-of-care (primarily clarithromycin or metronidazole based) eradication rate was 53%.
“The efficacy for RHB-105 was substantially greater due to rifabutin and the difference was statistically significant and clinically meaningful,” investigators concluded. “RHB-105 may be a new best in class, first line empiric treatment for H pylori infection, with the potential to serve an unmet need in an environment of increasing antibiotic resistance.”
In an interview with MD Magazine®, presenting author David Y. Graham, MD, MACG, professor of medicine and gastroenterology at the Baylor College of Medicine, discussed how this agent would fit into the current treatment landscape.
“There was opportunity, [and we] needed something that was new and this is an option because there's no resistance yet to rifabutin and very low resistance to amoxicillin,” he said. “There’s only 1 approved drug right now that works [for H pylori eradication]…[so] the key was to work out a combination that worked, and they came up with a combination that's all-in-one and convenient…[This approval would provide] another therapy that does work [and] is very well-tolerated.”
Graham also explained how the current treatment regimens have bred resistance and how RHB-105 could potentially solve that problem.
“The resistance comes because of misuse of the antibiotic…People don’t use rifabutin. It’s used for drug-resistant tuberculosis long-term; very few people get it,” he said. “Unless they start abusing it, resistance should stay very very low.”
The study, Rifabutin (RHB-105) Based Triple Therapy for Helicobacter pylori (HP) Infection Eradication: Results of Pivotal Phase 3 Multi-Center Study (ERADICATE Hp2), was presented Wednesday, October 30, 2019, at the American College of Gastroenterology Annual Scientific Meeting (ACG 2019) in San Antonio, Texas.