FDA pushes back decision date on Abeona’s pz-cel treatment for RDEB
Agency says its review of cell therapy won't be done by set date of May 25
The U.S. Food and Drug Administration (FDA) is pushing back its timeline for a decision on Abeona Therapeutics’ pz-cel (prademagene zamikeracel), saying the agency needs more time to complete its review of the cell therapy for recessive dystrophic epidermolysis bullosa, known as RDEB.
A decision by the FDA on the company’s biologics license application (BLA) for pz-cel had previously had a set date of May 25.
In a complete response letter, or CRL, to Abeona, the regulatory agency pointed to specific issues with chemistry, manufacturing, and controls — known together as CMC — on manufacturing and batch testing processes that must be addressed before the treatment can be approved, the company stated in a press release.
“While we are surprised and disappointed by this CRL, we are committed to providing the CMC information necessary to respond to the agency’s asks, with the goal of bringing pz-cel to patients with RDEB as quickly as possible,” said Vish Seshadri, PhD, Abeona’s CEO.
Pz-cel is being developed for RDEB, a type of epidermolysis bullosa. The genetic disease causes severe wounding of the skin. The treatment candidate has been granted orphan drug, rare pediatric disease, regenerative medicine advanced therapy, and breakthrough therapy designations from the FDA, all of which were meant to accelerate pz-cel’s clinical development and regulatory review.
Manufacturing process for RDEB therapy at issue in delay
The issues cited by the FDA as still under review were noted during a two-week site inspection, completed March 1, of Abeona’s manufacturing facility in Ohio.
Abeona said last month that it was already taking steps to address the agency’s concerns, and that pz-cel remained on track for an FDA decision on the set May date.
During a recent company webcast, Abeona said it had further discussed with the FDA plans to submit preliminary information by mid-May, and to provide full reports afterward.
However, with the set decision date just a month away, the FDA concluded that the proposed timing would not be sufficient to allow the agency to complete its review, the company said.
The FDA did not request in [its response letter] any new clinical trials or clinical data to support the approval of pz-cel. … And that is huge.
Importantly, according to Seshadri, regulators raised no concerns about the safety and/or effectiveness of pz-cel in people with RDEB.
“The FDA did not request in the CRL any new clinical trials or clinical data to support the approval of pz-cel,” Seshadri said during the webcast.
“And that is huge,” he added.
Now, Abeona is looking to address four main issues raised by the FDA, with Seshadri noting that the company expects to submit all of the requested data by no later than September.
“We are already hard at work generating the additional CMC information, and we expect that all of [the] FDA’s requests will be addressable in a reasonable timeframe,” Seshadri said in the release.
Developer expects all additional data to be submitted by September
Treatment with pz-cel, previously known as EB-101, involves first collecting a patient’s own skin cells, then modifying them in the lab. The cells are treated with a healthy copy of COL7A1, the gene mutated in RDEB, which is delivered aboard a modified and harmless retrovirus. The modified cells are then grown to form a fine sheet that can be surgically grafted onto the patient’s wounds.
In the webcast, Seshadri said the FDA specifically requested that the company adopt several strategies to ensure that sterility is maintained during manufacturing, in addition to validated sterility testing already in use by Abeona.
One such strategy is the implementation of a rapid sterility testing solution to allow detection of any contaminating microbes within the short shelf life of pz-cel.
The agency also requested that Abeona validate replication-competent retrovirus (RCR) testing in the company’s unique retrovirus manufacturing matrix, and adopt testing to confirm the identity of the skin cells as they are grown in the lab.
RCR testing checks for the unintended production of retroviruses that could make copies of themselves and potentially cause disease.
The CRL also noted “other deficiencies related to whole-cell DNA testing, container closure integrity test, visual examination, and certain raw material testing reports, which will also be provided in our BLA resubmission,” Seshadri said.
“We anticipate completing the BLA resubmission in the third quarter of 2024 with necessary updates to fully satisfy all the deficiencies outlined in the CRL,” Seshadri said in the release.
The BLA for pz-cel was based on data from a Phase 1/2a clinical trial (NCT01263379) and the Phase 3 VIITAL study (NCT04227106). Both trials showed that a single application of pz-cel on large, long-lasting wounds of children or adults with RDEB safely led to sustained healing and reduced pain after six months, regardless of how severe the affected areas were.
The application was accepted under priority review, a pathway that expedites the review of treatments with the potential to bring significant benefits to patients. It shortens the review period from the usual 10 months to about six months.
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