Enzyvant hit with CRL due to regenerative therapy manufacturing concerns

The US FDA has cited manufacturing concerns in a complete response letter (CRL) rejecting Enzyvant’s regenerative tissue therapy RVT-802.

RVT-802 is a tissue-based therapy in development for congenital athymia. While the candidate has been granted Breakthrough Therapy designation, Rare Pediatric Disease designation, Orphan Drug designation, and Regenerative Medicine Advanced Therapy (RMAT), the US Food and Drug Administration (FDA) has rejected the therapy due to manufacturing concerns.

Roivance Sciences subsidiary Enzyvant received the CRL this week and while there were no questions about the therapy’s safety or efficacy, the agency raised questions about how it is produced.

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“This is a novel therapy… There’s not some well-recognized method of manufacturing a therapy like RVT-802. It is complex,” CEO Rachelle Jacques told our sister publication Xconomy.

While specific details were not disclosed, Jacques said the questions raised can be resolved and the FDA rejection does not affect the firm’s plans to pursue approval in Europe, or to develop the therapy for other T cell disorders.

The candidate itself, developed in partnership with Duke University School of Medicine, is made using thymus tissue taken from babies undergoing cardiac surgeries.

After the donor tissue is screened for viruses or infectious diseases, it is processed to remove cells that are on their way to becoming T cells, and thus, reducing the risk of graft versus host disease. The thymus tissue is then implanted into an infant’s leg where it functions as the patient’s own thymus.

According to Reuters, Enzyvant plans to use contract development and manufacturing organizations (CDMOs) to produce RVT-802. This follows the strategy in place for its other candidate, RVT-801, a recombinant form of human acid ceramidase (rhAC), in early-stage development as an enzyme replacement therapy for patients with acid ceramidase deficiency manifesting as Farber disease.

RVT-801 will be manufactured by California-based CDMO Avid Bioservices after Enzyvant inked a deal with the firm in February 2018 for the supply of the candidate’s commercial drug substance. There is no suggestion Avid is being used for the production of RVT-802.