A new orally delivered investigational therapy could help curb the costly and often recurring infection.
A new study suggests a 4-component cocktail of antibodies may be able to Cloistridioides difficile infection (CDI) in many patients.
A pre-print version of a study by corresponding author James M. Roberts, MD, PhD, and colleagues, details how the therapy, dubbed LMN-201, was able to prevent CDI both in vitro and in vivo, in preclinical models. Roberts is the chief scientific officer and a cofounder at Lumen Bioscience, which is developing the therapy.
Roberts and colleagues wrote that despite the heavy toll CDI places on the healthcare system—with hundreds of thousands of cases each year—current therapies are only partially effective.
“Almost all antibody therapies have been developed and administered as monotherapies,” Roberts and colleagues wrote. “Antibody cocktails are relatively rare even though they have the potential to greatly increase efficacy.”
Even when patients are cured, the company noted, between 20-40% will experience a recurrence of CDI. The infection costs the US health system about $5 billion per year, they said.
One reason for the lack of antibody cocktails, the investigators wrote, is that it can be difficult to know how different types of antibodies will interact with each other.
“In contrast to the view that antibody synergies depend on unusual instances of cooperativity or allostery, we show that synergistic efficacy requires nothing more than that the antibodies bind independently to distinct epitopes on a common target,” they explained.
In a press release, Roberts said the technology could have wide-ranging implications.
“LMN-201 establishes a new paradigm for safe and highly potent biologic cocktails for disease targets within the GI tract,” he said.
He said other gastrointestinal-tract conditions that might be helped with antibody cocktails include Crohn’s disease, ulcerative colitis, metabolic diseases, and celiac disease.
One reason Roberts and others are excited is that the first cohort of their phase 1 pharmacokinetic trial for LMN-201 suggested that the therapy can be effectively delivered via capsule and still reach its target destination at or before the terminal ileum. The completion of a second cohort is expected soon.
In a statement to Contagion, the company said its eventual phase 2 study will focus on patients who were recently diagnosed with CDI and have begun standard antibiotic therapy. Rather than replacing antibiotics, they said LMN-201 could complement antibiotic therapy, to prevent recurrence of CDI.
LMN-201 is manufactured in recombinant spirulina, a type of algae commonly found in nutritional supplements. The therapy is then delivered in a dry powder of spirulina biomass, making it shelf-stable and scalable, the company added.
The company said the unique scalability of their product means they can leverage the technology to address diseases that are sometimes ignored by major drug developers, such as norovirus. They said the technology could also extend to treat illnesses beyond the gastrointestinal tract, such as obesity. Though obesity is not a GI disease per se, the disorder is related to diet.
“It turns out that—like obesity—there are many other systemic diseases and disorders that may have this kind of relationship with events in the GI tract,” the company told Contagion, citing neurological disorders and autoimmune diseases as 2 examples.