Niemann-Pick Disease Type C Gene Therapy Gets Rare Pediatric Disease Designation

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Earlier this year Bloomsbury Genetic Therapies met with the UK’s MHRA for a scientific advice meeting to discuss BGT-NPC.

Bloomsbury Genetic Therapies’ BGT-NPC, an investigational adeno-associated virus (AAV) vector-based gene therapy intended to treat Niemann-Pick disease type C (NPC), has received rare pediatric disease designation from the FDA.1

Earlier this year, on April 26, Bloomsbury met with the UK Medicines and Healthcare products Regulatory Agency (MHRA) for a scientific advice meeting.2 In the meeting, Bloomsbury and the agency discussed the company’s preclinical data package and plans for a registrational phase 1/2/3 clinical trial in the UK. The MHRA supported Bloomsbury’s plan to supplement a single toxicology and biodistribution rodent study with published data from other intrabrain AAV9 gene therapies, which would serve as precedent for the approach, without the need for any larger animal studies. Bloomsbury anticipates starting the aforementioned rodent study in 2024, pending the start of manufacturing efforts with a contract development and manufacturing organization partner.

“We are very happy to be granted this important designation by the FDA, following our great regulatory momentum and the progress with the program via our collaboration with University College London,” Adrien Lemoine, MSc, the co-founder and chief executive officer of Bloomsbury, said in a statement.1

BGT-NPC utilizes an AAV9 vector and is intended to be injected into the cerebrospinal fluid as a 1-time treatment in order to provide a functional copy of NPC1, the disease-targeted gene. Currently in the preclinical stage, it is being developed collaboratively with University College London (UCL), from which Bloomsbury launched as a spinout in October 2022.

In June 2023, Bloomsbury announced that an article covering earlier preclinical mouse model research had been published in Cells.3,4 The research tested the use of the novel, truncated NPC1 endogenous promoter in BGT-NPC. This novel promoter was incorporated because other promoters typically used in gene therapies are larger and might pose issues being transported in the AAV9 vector alongside the large NPC1 gene. The research demonstrated that the use of the novel promoter in NPC gene therapy yielded better outcomes in terms of NPC1 protein expression, survival, behavioral phenotypes, and neuropathology in NPC mouse models after intracerebroventricular injection into the central nervous system shortly after birth. Bloomsbury noted that it is currently conducting additional preclinical research in juvenile mice to prepare for the toxicology and biodistribution study.

“We are pleased to announce the publication of our work leading to the identification of a novel, minimal NPC1 promoter used in BGT-NPC, demonstrating the significant therapeutic potential of brain-targeted AAV-mediated gene therapy for the treatment of NPC1,” Ahad Rahim, PhD, a professor of translational neuroscience at UCL, the WellcomeChair in Pharmacology and the head of the Pharmacology Department at the UCL School of Pharmacy, who led the preclinical research, said in a June 2023 statement.3 “We look forward to continuing our efforts with our partner, Bloomsbury Genetic Therapies, to accelerate the translation of this program into the clinic and provide a novel, effective treatment to patients affected by this devastating disease.”

The granting of the rare pediatric disease designation is the latest in a recent series of regulatory designations for gene therapies that Bloomsbury has garnered in recent months. Earlier in August, the company received an orphan drug designation from the FDA for BGT-OTCD, an investigational AAV vector-based gene therapy intended to treat ornithine transcarbamylase deficiency.5 Prior to that, in May 2023, the Bloomsbury announced that it had received rare pediatric disease designation for BGT-DTDS, an investigational AAV vector-based gene therapy intended to treat dopamine transporter deficiency syndrome.6

REFERENCES
1. Bloomsbury Genetic Therapies receives rare pediatric disease designation from the U.S. FDA for BGT-NPC for the treatment of Niemann-Pick disease type C (NPC). News release. Bloomsbury Genetic Therapies Limited. August 21, 2023. Accessed August 21, 2023. https://bloomsburygtx.com/bloomsbury-genetic-therapies-receives-rare-pediatric-disease-designation-from-the-u-s-fda-for-bgt-npc-for-the-treatment-of-niemann-pick-disease-type-c-npc/
2. Bloomsbury Genetic Therapies completes successful scientific advice meeting with the MHRA regarding its BGT-NPC program. News release. Bloomsbury Genetic Therapies Limited. June 12, 2023. Accessed August 21, 2023. https://bloomsburygtx.com/bloomsbury-genetic-therapies-completes-successful-scientific-advice-meeting-with-the-mhra-regarding-its-bgt-npc-program/
3. Bloomsbury Genetic Therapies announces publication of article highlighting preclinical data from BGT-NPC program, supporting BGT-NPC as a potential treatment for Niemann-Pick disease type C. News release. Bloomsbury Genetic Therapies Limited. June 14, 2023. Accessed August 21, 2023. https://bloomsburygtx.com/bloomsbury-genetic-therapies-announces-publication-of-article-highlighting-preclinical-data-from-bgt-npc-program-supporting-bgt-npc-as-a-potential-treatment-for-niemann-pick-disease-type-c/
4. Hughes MP, Nelvagal HR, Coombe-Tennant O, et al. A novel small NPC1 promoter enhances AAV-mediated gene therapy in mouse models of Niemann–Pick type C1 disease. Cells. 2023;12(12):1619. doi:10.3390/cells12121619
5. 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 22, 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/
6. Bloomsbury Genetic Therapies receives rare paediatric disease designation from the U.S. FDA for BGT-DTDS for the treatment of dopamine transporter deficiency syndrome (DTDS). News release. Bloomsbury Genetic Therapies Limited. May 3, 2023. Accessed August 22, 2023. https://bloomsburygtx.com/bloomsbury-receives-rare-paediatric-disease-designation-from-the-u-s-fda-for-bgt-dtds-for-the-treatment-of-dopamine-transporter-deficiency-syndrome-dtds/
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