Synthetic Biologics loses breakthrough status after FDA reviews death imbalance in trial data

News of the withdrawal and rescinding of breakthrough designations is very rare, but data from the FDA show such events happen. (FDA)

Synthetic Biologics has lost its breakthrough designation for ribaxamase following a review of the data by the FDA. The review focused on an imbalance in patient deaths in a phase 2b trial of the drug, leading the FDA to conclude ribaxamase no longer meets the requirements for its breakthrough status.

Rockville, Maryland-based Synthetic voluntarily withdrew its breakthrough therapy designation following the review, although, given the FDA’s findings, that could be seen as the biotech jumping rather than waiting to be pushed. The FDA found the size of the safety database and study’s statistical treatment of dropouts precluded it from fully evaluating the imbalance in fatal adverse events. 

"The FDA agreed that underlying comorbidities in the patient population may have contributed to the observed disparity in deaths," a spokesperson for Synthetic said. "However, they indicated that these data were inconclusive to definitively exclude the possibility that ribaxamase treatment contributed to patient mortality risk in the ribaxamase phase 2b clinical. Synthetic Biologics and the FDA agreed that a larger clinical trial which evaluated efficacy and safety separately is required to provide conclusive evidence that ribaxamase does not adversely alter mortality risk in this patient population."

The fallout from the FDA’s findings means Synthetic is heading into phase 3 without a breakthrough designation and with a trial design tailored to the concerns raised earlier in development. Synthetic will collect data against separate primary safety and efficacy endpoints. The safety endpoint will look at mortality risk.

News of the withdrawal and rescinding of breakthrough designations is very rare but anonymized data (PDF) from the FDA show such events happen. Last year, the FDA rescinded three breakthrough nods and accepted the withdrawal of another two. Another eight designations were either pulled or rescinded from 2014 to 2016. This year has also seen at least one designation rescinded (PDF).

In contrast to the fanfare that accompanies the receipt of breakthrough designations, these reversals typically go unmentioned by the companies involved. The FDA, in keeping with its practice, is equally taciturn. 

The record number of breakthrough statuses withdrawn or rescinded last year suggest the FDA is enforcing the requirements as vigilantly as ever under commissioner Scott Gottlieb, M.D., although year-to-year comparisons are complicated by the limited dataset and growth in the overall number of breakthrough designations. 

Synthetic posted news of the withdrawal alongside a broader update on its R&D plans. The nanocap’s stock fell 12% in premarket trading on the back of the update.