Fecal transplant pill replaces antibiotics for serious infections for the first time

One hundred years ago, antibiotics revolutionized medicine. Bacterial infections were wreaking havoc, and the emergence of a drug capable of annihilating microbes led to an unprecedented improvement in life expectancy. Since then, the massive — and sometimes negligent — use of antibiotics has allowed bacteria to adapt to its attacks and antibiotic resistance is threatening to devalue medicines that have saved millions of lives. Now, the study of the intestinal microbiota, an ecosystem of microorganisms that coexist inside us in a complex balance, is making new treatments for infections possible.

This is the case with MBK-01, the code name of a drug to treat Clostridium difficile infections, which affects 124,000 hospitalized people in Europe every year. The drug is a pill made from the fecal transplants of healthy donors that manages to fight bacteria in a method different to the antibiotic. Instead of killing the organism that causes diarrhea, and along with it, the many other bacteria that are needed for good intestinal health, it introduces the balanced microbiota of a healthy patient. All these beneficial organisms counteract the excess C. difficile and restore health without wiping out the bacterial ecosystem. As a result, the patient is less prone to relapses.

The drug, developed by a small company called Mikrobiomik from the Spanish city of Derio, has passed a Phase 3 trial (the last in humans before approval), with positive results. In this study, which involved 92 patients with C. difficile from 21 centers in Spain, the pill showed no safety problems and was 15% more effective than fidaxomicin, the antibiotic usually used to treat this infection. What’s more, the trial also showed that people who took the fecal transplant pill had a lower recurrence of the condition than those who received the antibiotic.

In the United States, two microbiota therapies are already marketed for similar infections, one developed by Seres Therapeutics, which was the first approved fecal microbiota transplant pill in the world, and another developed by Rebiotix, which is introduced by colonoscopy. In both cases, the U.S. Food and Drug Administration approved their use for people with C. difficile, but only for patients who had already suffered relapses after taking antibiotics. The trial developed by Mikrobiomik would allow the pill to be used as a first option. “It is the first non-antibiotic antibiotic,” summarizes Juan Basterra, CEO of the company.

C. difficile is a bacterium that is difficult to kill. The bacillus forms spores that are able to survive for years in water or on the floor of a hospital, waiting for the right moment to find a host where it can thrive. In the body, the same thing happens. Even if the antibiotic kills the bacterial community, the spores can resist and trigger a relapse. “In a work published in 2013 in The New England Journal of Medicine it was shown that to combat C. difficile, rather than eliminating it with antibiotics, it was better to separate it, to make it become subdominant,” explains Francisco Guarner, digestologist and member of the scientific committee of the International Human Microbiome Consortium. “The problem with transplantation is that you put in a lot of unknown things, and [in 2019] one person died and another became very sick from one of these transplants. This triggered alarm and drew attention to the need to properly resolve the safety issues,” he adds.

Freeze-dried fecal microbiota transplantation, in pill format, “could revolutionize access and convenience for the treatment of C. difficile infections,” says Majdi Osman, a professor at Harvard University and medical director of OpenBiome, an organization working to improve the accessibility and safety of fecal microbiota transplants. For Osman, if the product is effective, a pill would make the treatment easier — not only because the method of administration is easier, but because it could be stored at room temperature.

However, the professor also points out that, for more severe cases, administration by colonoscopy “is still more effective” than pills. Still, Osman notes that “in people with severe infections, who may need several treatments, there may be an initial role for colonoscopy treatment and then doing the subsequent ones by oral capsule.” “More research is needed to understand the best route and the best dose,” he concludes.

“After completing this Phase 3 trial, we are very close to bringing it to the market. The EMA [European Medicines Agency] has already classified our product as an active substance,” he points out. In Spain, in addition to the participants in the company’s clinical trials, 40 people have taken the medicine, within the compassionate use of medicines program of the Spanish Agency for Medicines and Health Products (AEMPS), which allows patients in need to use a drug, even if it is not approved, and they are not in a clinical trial. Now, Microbiomik is looking for capital to expand its production capacity and workforce.

For the future, Mikrobiomik is testing its technology in diseases of the liver, intestine and as an aid in the treatment of colon cancer. Although the field of research is relatively new, there are already indications that fecal transplants could be useful in treating depression and a link has also been observed between the microbiome and some cardiovascular or degenerative diseases. After the revolution that improved the lives of millions by killing the bad microbes, a new transformation may be in the making thanks to pills that restore health by helping the good microbes.

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