The multiyear ORBEX clinical trial found that OM-85 did not reduce severe wheezing episodes or early childhood asthma diagnoses.
RT’s Three Key Takeaways:
- Trial Outcomes: The national ORBEX clinical trial demonstrated that treating high-risk infants with the oral bacterial extract OM-85 did not significantly decrease the incidence of severe wheezing or reduce asthma diagnoses by age 6 compared to a placebo.
- Rethinking the Hygiene Hypothesis: The study findings challenge longstanding interpretations of the hygiene hypothesis, indicating that oral microbial extracts alone may be insufficient to prevent allergic and respiratory airway diseases.
- Future Research Directions: Investigators plan to explore prenatal risk factors, epigenetic mechanisms, and alternative delivery approaches such as nasal sprays to determine whether treatments can be administered once asthma pathways are already active.
According to a study published in The Lancet, a national clinical trial led by researchers at the University of Arizona College of Medicine – Tucson found that treating young children with an oral bacterial extract did not reduce the risk of severe wheezing and respiratory illnesses that can precede asthma.
The trial, known as ORBEX, was launched in 2017 to evaluate whether an oral bacterial extract called OM-85 (Broncho-Vaxom) could provide immune system training to prevent asthma in high-risk pediatric populations. The research team was led by Dr Fernando Martinez, director of the Asthma and Airway Disease Research Center, and co-investigator Dr Wayne Morgan, professor of pediatrics and physiology at the University of Arizona.
“…We found no significant difference between the treatment and placebo groups,” said Fernando Martinez, director of the University of Arizona Asthma and Airway Disease Research Center. “We need to rethink what we have thought until now. That’s my real conclusion. There’s no easy solution for these complex diseases that are part of our time.”
According to the US Department of Health and Human Services (HHS), children under 5 are more likely than any other age group to visit the emergency department due to asthma, and wheezing lower respiratory illnesses remain a primary cause of pediatric hospitalizations.
Evaluating ORBEX Trial Findings
The double-blind investigation enrolled 822 children between the ages of 6 and 18 months across 11 US sites. Participants were classified as high risk due to a family history of asthma or a diagnosis of eczema. Children received either OM-85 or a matching placebo for 10 days per month over two years, followed by an extended observation period that concluded at age 6. Investigators extended the follow-up window from one to three years after treatment because the COVID-19 pandemic temporarily suppressed circulating respiratory viruses.
The study evaluated time to first severe wheezing episode requiring multiple rescue interventions or oral corticosteroids. Investigators reported no meaningful difference in time to the first illness between the cohorts. During the three-year post-treatment phase, 21% of participants in the OM-85 group experienced a severe wheezing episode, compared to 18% in the placebo group. Furthermore, clinical asthma diagnoses by age 6 were identical in both groups at 21%.
Rethinking the Hygiene Hypothesis
The trial was designed to evaluate the hygiene hypothesis, which posits that reduced exposure to microbes in modern, sanitized settings contributes to increased allergic conditions. Earlier smaller studies showed benefit with OM-85, but Morgan noted that those trials involved children already experiencing frequent wheezing, rather than asymptomatic high-risk infants. Investigators hypothesize that the therapeutic might only function as a treatment once disease pathways are activated, rather than as a primary preventative.
According to the study authors, future research will examine alternative delivery modalities, such as nasal sprays, alongside prenatal influences. Martinez noted that immune susceptibility may originate prior to birth through epigenetic modifications that alter gene expression in response to maternal exposures.
Funding for the ORBEX trial was provided by the National Heart, Lung, and Blood Institute (NHLBI), with supplemental support and study medication supplied by OM Pharma.
