UPDATED: Food or drug? FDA blasts Flagship-backed microbiome player’s ‘non-IND’ Covid-19 trial
When Kaleido Biosciences unveiled results from a multi-center, open label, controlled clinical study testing its microbiome product in Covid-19 patients back in March, the biotech touted it as a “non-IND” trial that yielded positive results and paved the way for an IND.
But it turned out that the FDA was not impressed with that tactic.
The agency has issued a warning letter to Kaleido blasting its “failure to submit INDs for the conduct of clinical investigations with an investigational new drug” that falls under section 505 of the federal Food, Drug, and Cosmetic Act. Kaleido now has 15 days to explain itself or report the actions it’s taken to prevent similar violations — or else face regulatory action.
“We are reviewing the letter currently and look forward to providing a response within the given timeframe and continuing our discussions with the FDA,” CEO Dan Menichella, to whom the letter was directly addressed, said in an emailed statement.
Kaleido was well aware of the FDA’s objections, according to the letter, which stated that inspector Kent Conforti had presented a Form 483 and discussed it with staff in early March.
Regulators received a response on March 23, the eve of Kaleido’s study result announcement, in which Kaleido argued that KB109, the synthetic glycan being tested in the study, was in fact “a food rather than a drug.”
Specifically, Kaleido argued that the investigations were conducted “to evaluate the effect of KB109 on the microbiome[,] as well as to determine the safety and tolerability of KB109 in the diseased population[,]” that is, human subjects with mild to moderate COVID-19, and thus it investigated KB109 for use as a food rather than a drug.
To support this argument, Kaleido asserted that it did not intend for these “food studies” to evaluate whether KB109 would be an effective treatment or mitigation for COVID-19; rather, Kaleido argued that the secondary endpoints in these studies were determinative of safety and tolerability. For this reason, Kaleido stated that KB109 was a food intervention, and consistent with Agency guidance, it was appropriate to conduct these studies without an IND in a population with COVID-19.
The protocol, dubbed Protocol K031-120 and Protocol K032-120, and Kaleido’s press releases suggested otherwise, the FDA said. Not only was Kaleido’s objective to compare the safety and efficacy of KB109 in combination with supportive self-care under quarantine against supportive self-care alone, the biotech also measured participants’ symptoms and healthcare utilization among other things like biomarkers and their gut microbiome structure.
To the FDA, that sounds a lot like the efficacy endpoints it has recommended in its guidances to help sponsors navigate developing Covid-19 treatments.
For Protocol K032-120, while some endpoints could be considered safety outcomes that might be evaluated only to ensure that treatment with KB109 was not worsening the course of COVID-19, other endpoints (for example, proportion of subjects experiencing hospital admission during the follow-up period, measures of healthcare utilization, and proportion of subjects with oxygen saturation below normal) clearly assessed the use of KB109 in combination with SCC for the treatment or mitigation of COVID-19.
The argument for describing KB109 as a medical food fails because no distinctive nutritional requirements have been established for Covid-19, which is a prerequisite for defining medical food, the FDA wrote. Besides, the studies went beyond “dietary management” and evaluated a host of other effects on Covid-19 infection.
“As Kaleido noted in its response to the Form FDA 483, whether an investigational article is a drug or a food depends on the intent of the investigation,” its letter read. And KB109 was used in these clinical investigations as a drug because it was “studied for use in the mitigation and treatment of COVID-19.”
The FDA asked Kaleido to get in line, address the deficiencies and set up procedures to ensure compliance with regulations in the future.
Editor’s Note: This story has been updated to incorporate a comment from Kaleido.