- HG004 is a one-time, direct-to-RPE treatment of inherited
retinal disease caused by mutations in the RPE65 gene
- ∼ 10-fold lower vector doses than other AAV2 gene therapy
clinical trials to be tested in this planned trial
- On track to initiate the multi-national trial by H1-2023
SHANGHAI and CLINTON, N.J., Jan. 28,
2023 /PRNewswire/ -- HuidaGene Therapeutics (HuidaGene), a
clinical-stage biotechnology company developing CRISPR-based
programmable genomic medicine, announces that the US. Food and Drug
Administration (FDA) has cleared its investigational new drug (IND)
application for the planned multi-national clinical trial of HG004
for the treatment of patients suffering from RPE65
mutation-associated inherited retinal dystrophies, a group of
genetic diseases caused by the mutations in RPE65 gene
affecting the retina and passed on to the children.
"We are thrilled to have received the IND clearance of our HG004
program from US FDA, marking our first IND clearance as a company
and our first retinal disorder program to reach clinical
development stage," said Xuan Yao,
Ph.D., Co-founder and Chief Executive Officer of HuidaGene.
"Clearance of this IND is a testament to the in-house pipeline
development capabilities and high-quality preclinical data
supporting HG004, as well as the strong CMC and analytics
capabilities through our partnership with WuXi Advanced Therapies.
The goal of the HG004 program is to develop a one-time, non-AAV2
gene replacement therapy to restore, treat, and prevent blindness
of children and adults with severe visual impairment or
blindness due to RPE65 mutation-associated retinopathies
globally."
Investigational HG004 is a novel ophthalmic injection that is
being developed to treat RPE65 retinopathies. Based on
the head-to-head preclinical comparison study of HG004 and
adeno-associated virus serotype 2 (AAV2) at the same dose, the
recovery of the retinal functions was increased by 67.6% (HG004)
and 35.8% (AAV2 products) when compared to the wild-type mice in
the Rpe65 knockout murine model at Week 17 after a single
injection. Therefore, HG004 demonstrates better transduction
efficiency of the retinal pigment epithelium (RPE) compared
with AAV2 and has the potential to lower the total vector doses,
which may reduce the risk of AAV vector-associated
immunogenicity or ocular adverse events in humans.
"We are excited by the promise of HG004 to offer a potential
transformative treatment better than AAV2-mediated gene replacement
therapy," said Hui Yang, Ph.D.,
Co-Founder and Chief Scientific Advisor of HuidaGene. "Our
extensive preclinical studies demonstrated superior transduction
efficiency and substantial restoration of vision loss at the RPE
layer when HG004 compared to AAV2 through our
independently-developed Rpe65 gene knockout murine
disease model, which is found to mimic the retinal phenotypes and
functions of patients with RPE65 mutation-associated
inherited retinal dystrophies."
"Our preclinical data supported our planned multi-national
clinical trial with a starting effective dose far lower than the
approved AAV2-hRPE65 gene therapy product and with less
volume need to be injected into the retina," said Dr. Xuan Yao. "We had already enrolled patients at
the end of 2022 in our investigator-initiated trial (IIT) in
China, and we saw a substantial
restoration of vision that were progressing toward complete
blindness even with nearly 25-fold lower vector doses of HG004 than
the approved AAV2-hRPE65 gene therapy product within
seven days after the single-injection of HG004."
About Multi-national Clinical Trial of HG004
HG004 will be evaluated in a multinational, multicenter,
multiple-cohort, dose-finding study of adult and pediatric subjects
with RPE65 retinopathies under one master protocol
in different countries. The purposes of the study are to
evaluate the safety, tolerability, efficacy, and long-term clinical
durability of a single injection of HG004 for up to 52 weeks.
Primary endpoints include adverse events, certain laboratory
measures, and ophthalmic examinations. The study will also assess
visual function via a multiluminance mobility test (MLMT), where
subjects will navigate a mobility course under
various light levels. After completing the primary study
period, subjects will continue to be assessed in a long-term
follow-up study of HG004.
About RPE65 Mutation-Associated Inherited Retinal
Dystrophies
Inherited retinal dystrophies (IRDs) are a group of rare
blinding conditions caused by mutations in any 1 of more than 250
genes. Leber's congenital amaurosis (LCA), severe early
childhood-onset retinal dystrophy (SECORD), early-onset severe
retinal dystrophy (EOSRD), and retinitis pigmentosa (RP), which may
all be grouped under the heading of RPE65
mutation-associated inherited retinal dystrophies, are considered
to represent a phenotypic continuum of the same disease. The
RPE65 mutation-associated inherited retinal dystrophies with
a typical onset between birth and five years of age exhibit
several common clinical findings, chiefly night blindness (light
staring with profound nyctalopia and nystagmus), progressive loss
of visual fields, and loss of central vision. The percentage of
patients (with biallelic RPE65 mutations) meeting the World
Health Organization (WHO) criteria for blindness increased with age
and reached 100% after the age of 40 years. Given the often severe
and early visual loss associated with RPE65 inherited
retinal dystrophies, other areas of development, including speech,
social skills, and behavior, may also be delayed.
About HuidaGene
HuidaGene Therapeutics is a global clinical-stage biotechnology
company focusing on discovering, engineering, and developing
CRISPR-based genetic medicine to rewrite the future of genomic
medicine. Based in Shanghai and
New Jersey, HuidaGene is committed
to addressing patients' needs globally with various preclinical
therapeutic programs covering ophthalmology, otology, myology, and
neurology. Company's CRISPR-based therapeutics offer the potential
to cure patients with life-threatening conditions by repairing the
cause of their disease. HuidaGene is committed to transforming the
future of genome-editing medicine.
For more information, please visit http://www.huidagene.com
or follow us on LinkedIn at
http://www.linkedin.com/company/huidagene
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