BioPharma, Pharma

FDA warns Kaleido Bio to test its Covid-19 candidate as a drug, not a medical food

The FDA issued a warning letter to Kaleido Biosciences alleging the company tested its experimental microbiome product in Covid-19 patients without submitting a formal clinical trial application. Kaleido claims the filing was not required because the product is a medical food, but the regulator doesn’t buy that argument.

A wind torn red warning flag indicating danger on an English beach.


The Covid-19 pandemic has spurred the pharmaceutical industry to cast a wide net for potential treatments, ranging from drugs approved for other indications to compounds still in development. Kaleido Biosciences’ test of its experimental gut microbiome therapy as a way to support Covid-19 patients now has the company in regulatory hot water for evaluating the product as a medical food, not as a drug.

Kaleido has been evaluating its microbiome product candidate, KB109, as a way to supplement supportive care of patients with mild-to-moderate Covid-19. KB109 is being tested in patients, but the company did not call the research a formal clinical trial. The company characterized the research as a “non-IND” clinical study, referencing the investigational new drug application (IND) filings that are required for tests of experimental drugs. The company said that the product is “generally recognized as safe,” or GRAS, an FDA designation that means an ingredient is safe according to an expert review.

The FDA isn’t buying it. The agency said that while some of the study goals are safety outcomes, others clearly assess the use of KB109 in combination with supportive care “for the treatment or mitigation of Covid-19.”

The warning letter to Lexington, Massachusetts-based Kaleido was posted to the FDA’s website this week. According to a regulatory filing for the publicly traded company, the correspondence was received on Aug. 27. In that filing, Kaleido noted that none of the FDA’s findings relate to the conduct or the oversight of the studies or the data, adding that the company is “coordinating with the FDA and intends to continue with its plans to submit an IND for KB109 in support of future clinical research.”

Kaleido calls its product candidates microbiome metabolic therapies (MMTs), a descriptor it applies to both drugs and food products, including medical foods. These company says these MMTs are a collection of molecules that affect the microbiome, driving the function and distribution of an organ’s existing microbes.

Before the pandemic, Kaleido was developing KB109 as a way to prevent infections in patients before they undergo hematopoietic stem cell transplants. Last year, the company announced it would broaden KB109’s scope, exploring application of that MMT for use in patients with mild-to-moderate Covid-19. The company framed KB109 as product that Covid-19 patients would be able to take in their homes.

Kaleido tested KB109 in an open-label study enrolling 350 patients; 181 of them received the Kaleido product plus self-supportive care while 169 patients received self-supportive care alone. In March, the company reported positive results showing that the group given KB109 had fewer hospitalizations, emergency room visits, and urgent care visits. Based on those results, the company said at the time that it planned to file an IND—that’s the formal clinical trial paperwork—to evaluate the microbiome product in a pivotal study in mild-to-moderate Covid patients who are at risk of prolonged symptoms.

According to the warning letter, Kaleido contended that its study of KB109 in Covid patients evaluated the product candidate as a medical food. Medical foods are products formulated for the dietary management disease. Developing a product as a medical food can be a faster way to the market, as medical foods don’t need to go through the three phases of clinical testing required of drugs. None of Kaleido’s products have been formally designated medical foods, but the company has been considering it.

“In parallel with our development of MMT product candidates for therapeutic indications, we are exploring the development of some of our product candidates as medical food products,” Kaleido stated in its 2020 annual report. “To date, we have not elected a product candidate to develop and market as a medical food and may never elect to do so.”

The company acknowledges the risk of the medical food route, going on to state in the annual report that the FDA may determine that Kaleido’s product candidates cannot be marketed as medical food, or do not meet medical food requirements. That’s exactly what the regulator did with KB109.

The FDA warning letter, which refers to the Kaleido microbiome product as a drug, was based on the findings of inspections conducted from Feb. 24 to March 3. The investigator found that Kaleido failed to file an investigational new drug application before starting a clinical trial. According to the warning letter, Kaleido intended to argue that the clinical studies evaluated KB109 as a medical food. But the FDA said that argument fails to meet the term’s definition, which states that these products are for the dietary management of a disease with distinctive nutritional requirements. “No such distinctive nutritional requirements have been established for Covid-19,” the FDA said in the letter.

Kaleido has 15 days from the Aug. 27 receipt of the warning letter to respond to the FDA. In the meantime, KB109 isn’t the only product candidate that Kaleido has evaluated in humans without formally submitting a clinical trial application. The test of KB295, which the company is evaluating for use in the inflammatory bowel disorder ulcerative colitis, is another non-IND study. The company said last month that it expects preliminary data from that study will be available by the end of the third quarter of this year.