From The Editor | July 2, 2019

Orchard Therapeutics Tackles ADA-SCID, MLD, And Much More


By Erin Harris, Editor-In-Chief, Cell & Gene
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On the heels of our sister print publication, Life Science Leader’s cover story on the whirlwind rise of Orchard Therapeutics, I had the opportunity to talk to company’s Co-Founder and Chief Scientific Officer, Dr. Bobby Gaspar about how the company has developed innovative gene therapies to treat CNS diseases, such as metachromatic leukodystrophy (MLD), tackle ADA-SCID, and more.

But, first — some background information. Orchard Therapeutics is a commercial-stage biopharmaceutical company with U.K.- and U.S.-based offices, and the company is dedicated to transforming the lives of patients with serious and life-threatening rare diseases through innovative gene therapies. Dr. Gaspar is a Professor of pediatrics and immunology at the UCL Great Ormond Street Hospital Institute of Child Health, London. “Our approach differentiates from other gene therapies in that we develop ex-vivo autologous gene therapies, using an individual’s own gene modified hematopoietic stem cell (HSC) gene therapy for the treatment of MLD and other disorders,” explains Gaspar.

Dr. Bobby Gaspar, Co-Founder and Chief Scientific Officer, Orchard Therapeutics
Dr. Gaspar has personally led multiple clinical trials showing that HSC gene therapy can successfully correct genetic defects in immune deficiencies like ADA-SCID — a very severe condition in which babies are born without immune cells. According to the U.S. National Library of Medicine, Adenosine deaminase (ADA) deficiency is an inherited disorder that damages the immune system and causes severe combined immunodeficiency (SCID). People with SCID lack virtually all immune protection from bacteria, viruses, and fungi. They are prone to repeated and persistent infections that can be very serious or life-threatening. These infections are often caused by opportunistic organisms that ordinarily do not cause illness in people with a normal immune system. “Children born with ADA-SCID have many problems, and bone marrow transplants using a donor’s HSCs are not always a viable solution,” explains Gaspar. “If the ADA-SCID child has a sibling, the child has an 85% chance of survival, yet, lesser-matched donors drop that success rate to 50%. We started our gene therapy program by successfully treating our first patient in 2003. Improved vectors came later, and since that time, we have been treating patients at Great Ormond Street Hospital in London and at UCLA. Our program has treated over 62 patients — with a 100% survival rate. Contrast our gene therapy treatment to bone marrow transplantation. More than 95% have responded to our gene therapy treatment and have been able to stop medication as a result.

Given the long-lasting effect of Orchard Therapeutics’ ex vivo autologous HSC gene therapy, Gaspar and his team aims to file MAA submission for MLD with the EMA 1H20, followed by FDA submission. For ADA-SCID, Orchard is looking at a rolling BLA submission with the FDA expected to initiate H1 2020, followed by MAA submission. “For me, the bigger picture perspective is that we’re able to correct a whole series of diseases — neurometabolic disorders, primary immune deficiencies, and red blood cell disorders, etc. using the same genetically modified hematopoietic stem cell approach,” says Gaspar. “Because of the self-renewing capability of engrafted gene modified HSCs, our approach has the potential to be a curative treatment, creating a sizeable shift in the way we practice medicine and the way we treat these disorders. Considering the amount of EMA and FDA approvals as of late, gene therapy is changing modern medicine.”