MGB Biopharma has reported positive results from a phase II trial showing that its antibacterial treatment for Clostridium difficile infections cured 100% of the patients, who showed no recurrence four weeks after.
The bacterium Clostridium difficile causes life-threatening infections in the intestine and is the most common cause of diarrhea. Current treatments against it are mostly bacteriostatic — meaning that they prevent the bacteria from reproducing rather than killing them.
“Recurrence is unacceptably high with current bacteriostatic treatments, occurring in up to one-third of patients treated with these mainstay therapies,” said Chris Wardhaugh, CBO of MGB Biopharma, which is based in Glasgow, Scotland.
These treatments usually need 24 hours or more to take effect, giving C. difficile plenty of time to form spores. In the form of spores, the bacteria are resistant to treatment and are able to infect the intestine again once the treatment is over.
MGB Biopharma is developing a new antibacterial that kills the bacteria within just one hour of its administration, thus preventing recurrence. “It is the only drug, either in clinical development or in current use, that is able to kill C. difficile bacterial cells in their vegetative form before they are able to form spores,” Wardhaugh told me.
The company has just completed a phase II trial testing different dosages of the drug in 34 patients. At the 250mg dose, given twice a day over the course of 10 days, 100% of the patients were cured of their C. difficile infection, and none showed recurrence four weeks after.
MGB Biopharma now plans to test the drug in a larger phase III study, where the prevention of recurrence will be measured for a period of eight weeks. If everything goes well and the company finds partners or investors to take the compound further, Wardhaugh estimates that the drug could reach the market by 2024.
The drug candidates developed by MGB Biopharma have a novel mechanism of action. The compounds bind to the minor groove of the DNA double helix, preventing it from interacting with other molecules and thus killing the bacteria. Results to date have shown this is effective against the most virulent strain of C. difficile, which is resistant to most current therapies. In addition, its effect on the gut microbiome is not as harsh as that of other treatments.
This mechanism of action has the potential to address a wide range of infections caused by bacteria, fungi, and viruses alike. MGB Biopharma has evidence that its drugs are effective against the hepatitis C virus and aspergillus fungi. According to Wardhaugh, its compounds are about to enter screening to determine if they are effective against Covid-19.
In the context of the current pandemic, new anti-infectives may prove essential to prepare and respond to any new threats. “With a pandemic on the scale of Covid-19, it is possible that a sizable number of patients with secondary infections will suffer from resistant infections that are difficult to treat,” said Wardhaugh, citing a recent study that showed that 50% of patients with Covid-19 who died in Wuhan had secondary bacterial infections.