Dating to a 2019 clinical hold of a phase 3 trial, getting its gene therapy prademagene zamikeracel (pz-cel) across the FDA finish line has been a challenge for troubled Abeona Therapeutics.
Now the wait continues as the FDA has rejected the treatment, sending the Cleveland-based company a complete response letter (CRL), specifying chemistry, manufacturing and controls (CMC) issues that must be addressed.
The topical treatment was targeted for approval on May 25 of this year for patients with recessive dystrophic epidermolysis bullosa (RDEP), a rare genetic condition that causes severe blistering of the skin.
“While we are surprised and disappointed by this outcome—especially given the positive results of our two clinical studies—I want to say that we believe the CRL provides a clear roadmap to bring this important product to patients as soon as possible,” Abeona CEO Vishwas Seshadri, Ph.D., said during a conference call Tuesday morning.
Seshadri, who became the company’s fifth CEO in a span of less than four years when he took over in 2021, was quick to point out that there were no efficacy or safety issues identified in the CRL about pz-cel.
“And that is huge,” Seshadri said, adding that the company expects to submit CMC information to the FDA in the third quarter of this year, with the best-case scenario for approval being in the first quarter of 2025.
After revealing the CRL in a press release on Monday afternoon, Abeona’s share price dropped by 47% by mid-morning on Tuesday.
Abeona had hoped that a meeting with FDA on March 21 and commitments to provide CMC data before the PDUFA date and post-approval validation reports would keep pz-cel on track. But the FDA said in the CRL that the proposed timing of the data submission would not allow sufficient time for FDA to complete its review.
“The necessary CMC information requested in the CRL pertains to certain validation requirements for manufacturing and release testing and includes observations that arose in the pre-license inspection,” Seshadri said.
That inspection took place in February and resulted in a Form 483 which included observations related to process controls.
After going into surprising detail on four CMC issues that need to be addressed, Seshadri said that with the exception of one assay “everything is standard, routine practice that is applicable to most, if not all, biological products and those assays need to be adapted to our matrix.”
Less than a year ago, Krystal Biotech became the first company to win approval for a DEP treatment, scoring with Vyjuvek. The approval covers a more mild form of the disease. Abeona's effort with pz-cel is to treat the more severe recessive form of DEP.