Despite encouraging clinical data for investigational therapy OTL-101, manufacturing issues have posed a significant roadblock, Orchard Therapeutic’s CEO writes.
OTL-101 is an investigational ex vivo autologous gene therapy intended to treat adenosine deaminase severe combined immunodeficiency (ADA-SCID), a rare and often lethal pediatric disorder caused by mutations in the ADA gene.
Results with the therapy have been promising – back in May 2021, Orchard reported that OTL-101 provided 100% overall survival and 95% even-free survival following a single treatment.
However, in a recent letter Orchard CEO Bobby Gaspar said that “Although the clinical data for investigational OTL-101 are very encouraging, we have encountered technical issues specific to the commercial-grade manufacturing processes for this particular therapy that must be addressed before we, or any other entity, could progress the program toward a regulatory submission. Without the ability to reliably manufacture OTL 101 at a commercial standard there is no way to receive FDA approval for the gene therapy. We have actively worked with CIRM, UCLA, UCL and our external manufacturing partners to determine potential solutions to address these manufacturing requirements. In addition, we have sought partners willing to invest to help us take this work forward, but we have not identified a viable path forward on either front.”
Gaspar goes on to acknowledge the importance of OTL-101 to the ADA-SCID community, and states that Orchard will continue to support its academic partners in continuing to treat patients under a compassionate use program, and will make the data and IND application available.
Orchard will now terminate their collaboration on the drug with the University of California, Los Angeles (UCLA) and University College London (UCL), and intend to “facilitate a smooth transfer of OTL-101 back to them”, Gaspard adds.
Donald Kohn, who developed the therapy at UCLA, commented in an interview that he will seek permission from the FDA to treat patients at UCLA under the agency’s expanded access program “as soon as possible.” UCLA and UCL will also be seeking a new commercial partner, Kohn added.