FiH trial of new immunotherapy approach shows efficacy in antibiotic resistance

Human polyclonal antibodies show promise as effective treatment.

“This study provides the first clinical evidence showing the human polyclonal antibody therapeutic - produced from our natural DiversitAb immunotherapy platform - is safe, and provides an option for recalcitrant infection resistant bacteria where antibiotics and multiple other therapies were ineffective,” said Eddie J. Sullivan, SAB Biotherapeutics president and CEO.

“This is an important step in furthering the development of this platform technology in infectious disease, including antimicrobial resistance,” he continued.

The trial, conducted at Brigham and Women's Hospital, involved a patient who suffered from a chronic infection caused by antibiotic-resistant bacteria. Mycoplasma hominis can be an infectious pathogen in immunosuppressed individuals. The patient was diagnosed with M. hominis septic polyarthritis in 2009 and was treated with multiple courses of antibiotics with no improvement. A target-specific human polyclonal antibody was pursued as a potentially more effective therapeutics strategy.

SAB’s new immunotherapy approach – The DiversitAb platform – leverages transchromosomal (Tc) bovine that have been genetically designed to produce fully human polyclonal antibodies (IgG) in response to a bacteria, virus or toxin. To create the targeted treatment, SAB vaccinated a Tc bovine with inactivated isolates of the patient’s bacteria (M. hominis). After 10 days the antibodies began circulating in the bovine blood stream and were harvested in plasma over several weeks.

The plasma was purified in the company’s cGMP manufacturing facilities to isolate the antibodies – designated SAB-136. The patient – the first to be treated with human polyclonal IgG harvested from Tc bovine – received infusions to combat the infection.

After one year, the high-dose therapy resulted in reduced M. hominis burden and improved clinical parameters. The infusions were well tolerated and with no significant adverse events. Safety was assessed with laboratory values, physical exam and subjective reports. Therapeutic efficacy was evaluated with samples collected from the primary infection site, and laboratory studies to monitor inflammation as well as a patient journal.

“This research demonstrates the potential for expanding treatment for immune deficient patients suffering from infections, which may have low coverage in current antibody replacement therapies,” said Duane Wesemann, a physician in the Rheumatology, Immunology and Allergy department at BWH and an Assistant Professor of Medicine, Harvard Medical School and principal investigator on the study.

“The use of DiversitAb platform begins to explore the relevancy for other patient populations in the setting of chronic, multi-drug resistant infections or viral infections for which there is no effective treatment or prevention strategy,” he added.

SAB’s first two immunotherapies targeting seasonal influenza and MERS-CoV are in clinical trials, with other infectious disease, oncology and autoimmune targets in development.

“With the advancements of modern medicine–and even recent immunotherapies–there are still many human health conditions without solutions,” concluded Sullivan. “Our hope is that our platform can provide a new rapid response and effective treatment for many of these patients.”