Vedanta brings home a win for lead microbiome program, passing a PhII test and clinching BARDA investment
Vedanta Biosciences wrapped up a Series D about two months ago to advance its microbiome research, but it’s not content to rest on its laurels.
The Cambridge, MA-based biotech claimed a win in a Phase II study treating Clostridioides difficile infection, saying its lead program achieved a statistically significant reduction in recurrences after eight weeks compared with placebo. It’s a result that ostensibly impressed the US government as the study results triggered a $23.8 million option from BARDA.
“We were already getting BARDA support, but the additional support we’re getting now, the $23.8 million is moreso going toward the Phase III study,” CEO Bernat Olle told Endpoints News in an interview.
Vedanta still has to sit down with the FDA to agree on a study design, Olle added, but noted it will likely involve the same patient population.
Olle and his team had been working on the candidate known as VE303, an oral drug comprising eight different bacteria strains designed to provide resistance to C. difficile. The Phase II study enrolled 79 patients and randomized them between a low dose, high dose and placebo group.
The high dose achieved the primary endpoint. In the active arm, patients saw a 13.8% C. difficile recurrence rate compared to 45.5% in the placebo group, with researchers using a combination of measurement tools to detect infection. The result proved a greater than 80% reduction in the odds of a recurrence, good for a p-value of p=0.0077.
Olle highlighted that the different tools used in the primary are the norm for these kinds of studies. Rather than only use toxin testing, Olle said Vedanta also looked at PCR testing in its endpoint analysis. And when patient samples were unavailable for testing, Vedanta relied on a clinician’s diagnosis.
Researchers desired a broader definition of what constitutes a recurrence because toxin testing is inherently inaccurate, Olle said. The tests can miss between 20% to 50% of positive cases if patient samples are not immediately frozen in transfer.
“The sample starts degrading right away,” Olle said. “Those are patients that have C. difficile, but … by the time you get the result you only capture a portion of them.”
To hammer this point home, Vedanta also measured the proportion of patients remaining recurrence-free after eight weeks using only the toxin testing. An analysis looking at the difference between the 86.2% of those in the high-dose cohort who did not see a recurrence, and the 54.5% of placebo patients, did not prove statistically significant.
The result is the “broadest and most comprehensive” definition of C. difficile infection recurrence, Olle said.
Vedanta is continuing to build out a manufacturing facility to prepare for Phase III and potential commercialization, remaining on track to complete it by the end of 2021. Should the Phase III study validate what researchers saw with Tuesday’s results, Olle says it will hopefully be enough for an FDA approval.
At that point, Vedanta could be producing about 1 million doses per year. With support from BARDA, Olle expects some government investment to build the national security stockpile in case of an outbreak.
After many investors fled the microbiome space following a Seres Therapeutics flop in 2016, cash has slowly started coming back to the field. In May 2020, Rebiotix presented positive data from a placebo-controlled study for its own C. difficile transplant therapy, and in July, after Seres found promising results with a new tack, Nestlé dropped $525 million to fund development for their lead microbiome treatment.
Pfizer also got in on the action, having invested $25 million in Vedanta back in January to help advance its slate of IBD programs. With the biotech now past a Series D and having a positive Phase II result, questions about an IPO will abound. Olle left the door open but didn’t give away many hints to his plans.
“At the stage that we are at, we’re open to all kinds of financing,” Olle said.
Correction: This article has been updated to correct information about the nature of testing for C. difficile. A combination approach using toxin testing, PCR testing and clinician diagnosis is the norm.