Ornithine Transcarbamylase Deficiency Gene Therapy Trial Begins Recruitment

Bloomsbury Genetic Therapies has initiated recruitment in its phase 1/2 HORACE clinical trial (Halting Ornithine transcarbamylase deficiency with Recombinant AAV in ChildrEn;NCT05092685) of its investigational BGT-OTCD gene therapy for the potential treatment of ornithine transcarbamylase deficiency (OTCD).1

“OTCD is a devastating disease, particularly in the paediatric population. Current medical management of children with OTCD and dietary protein restriction do not prevent recurrent metabolic crises and don’t fully address the sub-clinical chronic neuronal damage caused by elevated blood ammonia levels, and its impact on children’s neurological development. I am therefore very pleased that recruitment has been initiated in the HORACE trial and look forward to evaluating BGT-OTCD as a potentially curative solution for children with OTCD,” principal investigator Anupam Chakrapani, MD, Consultant, Metabolic Medicine, Great Ormond Street Hospital (GOSH), said in a statement.¹

HORACE is an open-label, safety, efficacy and dose-finding trial and will enroll up to 12 patients aged between 0 and 16 years old diagnosed with OTCD. University College London, the company’s collaborator and sponsor of the trial, is initiating the trial at a single treatment site, GOSH in London, UK, with 3 further referring UK sites: Evelina London Children’s Hospital, Royal Manchester Children’s Hospital and Birmingham Children’s Hospital.

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“The initiation of our first clinical trial just a year after Bloomsbury’s launch is a landmark moment for us. BGT-OTCD is a highly differentiated gene therapy candidate for OTCD, relying on the best-in-class capsid AAV-LK03, whose efficacy, durability and safety has already been illustrated in the clinic in haemophilia A clinical trials, and we believe it has curative potential for both paediatric and adult patients suffering from OTCD,” said Adrien Lemoine, cofounder and Chief Executive Officer, Bloomsbury, added.¹ “We look forward to UCL sharing initial clinical data with the OTCD community in due course.”

BGT-OTCD is an adeno-associated virus (AAV-LK03) gene therapy delivered in a single intravenous injection. The therapy received orphan drug designation from the FDA in August 2023.²

“People with this disease suffer from symptoms including vomiting, impaired voluntary movement and progressive lethargy, which can all progress to brain damage, coma or death if left untreated. The capsid used in this investigational AAV gene therapy, AAV-LK03, was selected for its enhanced ability to transduce human hepatocytes, and in particular periportal hepatocytes where the urea cycle preferentially takes place. We hope the trial will show that BGT-OTCD could provide sustained curative effect following a single administration even in children with a growing liver,” Chakrapani said in a statement following the United Kingdom’s Medicines and Healthcare products Regulatory Agency clearing Bloomsbury’s clinical trial application.³

REFERENCES

1. Bloomsbury Genetic Therapies announces initiation of recruitment in phase 1/2 HORACE clinical trial of investigational gene therapy BGT-OTCD for the treatment of ornithine transcarbamylase deficiency (OTCD). News release. Bloomsbury Genetic Therapies. November 16, 2023. https://bloomsburygtx.com/bloomsbury-genetic-therapies-announces-initiation-of-recruitment-in-phase-1-2-horace-clinical-trial-of-investigational-gene-therapy-bgt-otcd-for-the-treatment-of-ornithine-transcarbamylase-deficiency/
2. Bloomsbury Genetic Therapies receives orphan drug designation from the U.S. FDA for BGT-OTCD for the treatment of ornithine transcarbamylase deficiency (OTCD). News release. Bloomsbury Genetic Therapies Limited. August 9, 2023. Accessed August 18, 2023. https://bloomsburygtx.com/bloomsbury-genetic-therapies-receives-orphan-drug-designation-from-the-u-s-fda-for-bgt-otcd-for-the-treatment-of-ornithine-transcarbamylase-deficiency-otcd/
3. Bloomsbury Genetic Therapies announces clinical trial application accepted by U.K. regulatory agency to initiate phase 1/2 gene therapy trial of BGT-OTCD for the treatment of ornithine transcarbamylase deficiency (OTCD). News release. Bloomsbury Genetic Therapies Limited. December 7, 2022. Accessed August 18, 2023. https://bloomsburygtx.com/bloomsbury-genetic-therapies-announces-clinical-trial-application-accepted-by-u-k-regulatory-agency-to-initiate-phase-1-2-gene-therapy-trial-of-bgt-otcd-for-the-treatment-of-ornithine-transcarbamylas/