FDA Grants Rare Pediatric Disease Designation for Bloomsbury’s Gene Therapy to Treat Ornithine Transcarbamylase Deficiency

Rare Daily Staff

The U.S. Food and Drug Administration has granted Rare Pediatric Disease designation to Bloomsbury Genetic Therapies’ for its experimental therapy BGT-OTCD, a liver-targeted gene therapy for the treatment of ornithine transcarbamylase deficiency.

Ornithine transcarbamylase deficiency (OTCD) is a rare, X-linked genetic disorder that is characterized by complete or partial lack of the OTC enzyme. OTC is a key component of the urea cycle and patients with OTCD accumulate nitrogen waste in the form of excess ammonia (hyperammonemia) in the blood, causing hyperammonemic decompensations with symptoms including vomiting, impaired voluntary movement and progressive lethargy. If left untreated, these may progress to coma and life-threatening complications. While later onset disease can occur in adults with a milder form of the disorder, symptoms present within a few days of birth of males with severe OTCD.

Current standard of care involves protein-restricted diets and ammonia-scavenger medications; however, these approaches can have a significant impact on patients’ quality of life and patients still face lifelong risk of decompensation and neurological damage resulting in intellectual disability, developmental delays, and movement disorder. Liver transplant is the only curative option, but is often unavailable and comes with significant morbidity/mortality risk and lifelong immunosuppression and arginine supplementation.

“Current medical management of OTCD patients and dietary protein restriction do not prevent recurrent metabolic crises, with hyperammonemia leading to neurological damage,” said Paul Gissen, professor of Metabolic Medicine and head of Gene and Stem Cell Therapy at UCL Great Ormond Street Institute of Child Health. “With the highest unmet medical need seen in the pediatric population, we are pleased to see this recognition from the FDA as we complete our preparations for the HORACE trial.”

In May, the UK Medicines and Healthcare Products Regulatory Agency (MHRA) approved the clinical trial application submitted by Bloomsbury’s collaborators at University College London, to initiate a phase 1/2 clinical trial of BGT-OTCD in pediatric patients diagnosed with OTCD, which is expected to begin enrolment in the United Kingdom in the third quarter of 2023.

BGT-OTCD is a liver-targeted AAV-LK03 gene therapy designed to provide a potentially curative solution to OTCD patients following a one-time intravenous injection.  AAV-LK03 was selected for its high tropism for liver cells and its success in other liver disorders such as hemophilia A. BGT-OTCD has been granted orphan drug designation for the treatment of OTCD by the European Medicines Agency (EMA).

“OTCD is usually diagnosed during childhood, but we intend to investigate BGT-OTCD in both pediatric and adult populations, since its superior efficacy profile bears the promise of a potentially curative solution for all patients” said Adrien Lemoine, co-founder and CEO of Bloomsbury. “We look forward to leveraging the benefits that this new designation brings to the program.”

The FDA grants Rare Pediatric Disease designation for serious or life-threatening diseases which affect fewer than 200,000 people in the United States and in which the serious or life-threatening manifestations primarily affect individuals less than 18 years of age. If a Biologics Licensing Application for BGT-OTCD for the treatment of OTCD is approved by the FDA, Bloomsbury may be eligible to receive a Priority Review Voucher (PRV) that can be redeemed to receive a priority review for any subsequent marketing application, or may be sold or transferred. Most recently, Sarepta Therapeutics sold a PRV for $102 million.

Photo: Adrien Lemoine, co-founder and CEO of Bloomsbury