The US FDA has left the door open for Provention Bio’s teplizumab as a way to delay or prevent type 1 diabetes – but vague hopes for the future were not enough to prevent a 40% slide in Provention’s value yesterday.
The agency said it had identified “deficiencies” in the group's BLA that preclude discussion of labelling and post-marketing requirements for the anti-CD3 MAb “at this time”. Provention was quick to point out that this was not the FDA’s final word on the review. But pharmacokinetic inconsistencies are also worrying, and could spell a regulatory delay, if not a rejection.
It might not bode well for Provention that the wording used by the FDA is very similar to that employed by the agency during its review of another project, Acadia's Nuplazid, which recently received a complete response letter for dementia-related psychosis.
In regard to teplizumab, in addition to the undisclosed deficiencies in the BLA, the FDA also said it would need more data on the project's pharmacokinetic profile, having examined data submitted by Provention from its pharmacokinetic and pharmacodynamic bridging study.
This trial had compared the drug substance, manufactured by AGC Biologics, that Provention plans to sell, against the old product that had been made by Lilly, data on which Provention has used as part of the teplizumab BLA.
Provention says these projects are not biosimilars but equivalent antibodies produced from the same cell lines and following the same protocol, just at different manufacturing sites.
The FDA has come to a different conclusion, telling Provention that the two substances’ pharmacokinetics are not comparable. That something like this might have been coming had been hinted at by Provention’s disclosure a few months ago that the area under the curve for the AGC project was lower than seen with Lilly's, suggesting a slightly faster clearance from the blood with the former.
The different pharmacokinetic profiles of the two antibodies is a major concern, since both are being used in the company’s ongoing Protect trial in newly diagnosed type 1 diabetes. Data from Protect are expected next year (Provention claims success where Lilly failed, June 10, 2019).
More clarity on the situation might come with teplizumab's adcom, which will proceed as scheduled on May 27. But a decision on approval could be delayed by around a year from the current Pdufa date of July 2, Leerink analysts believe.
And this is the upside scenario. Unless Provention can convince the regulator that the two antibodies have sufficiently similar pharmacokinetics after all another CRL could be in the offing.