On January 26, 2022, pertaining to the announcement of Chinese CDE (Center for Drug Evaluation) official website, the clinical trial application of the AAV2-RPE65 gene therapy preparation LX101 Ophthalmic Injection independently developed by uBriGene’s partner Innostellar Biotherapeutics Ltd. has been approved by the CDE of National Medical Products Administration (approved project number: CXSL2200048).
What is LCA?
LCA (Leber congenital amaurosis) has the earliest onset and is the most severe type of hereditary retinopathy. Most patients with LCA begin to have severe visual impairment in infancy or childhood, and due to progressive retinal degeneration, become completely blind in their 30s and 40s.
There is currently no effective treatment for LCA, and it was not until the rapid development of gene therapy in recent years that a treatment for this severe retinal genetic disease was available.
The first FDA-approved gene therapy, Luxturna, in 2017, was for the treatment of LCA Type 2 (LCA2) caused by biallelic mutations in RPE65. The therapy was approved by the EMA in November 2018. LX101 Ophthalmic Injection was the first gene therapy clinical trial application for LCA submitted in China.
Key Milestones
In June 2021, Innostellar Biotherapeutics launched the first gene therapy clinical study for LCA in China to evaluate the overall safety and efficacy of a single subretinal injection of LX101 Ophthalmic Injection in the treatment of specific types of LCA. On June 24, the first patient was successfully treated at the Eye Center of Shanghai First People's Hospital. LX101 carried the target gene fragment into cells whose function is affected by gene mutation and performed functional repair in it.
On September 16, 2021, LX101 completed subretinal injection in the first LCA-affected minor.
In December 2021, according to the public information, LX101 showed good safety and efficacy records in many patients. The company said more patients would be enrolled in clinical trials in 2022.
On January 26, 2022, the clinical trial application of LX101 ophthalmic injection was accepted by CDE.
Commercialization Considerations
Continuity, comparability, and repeatability are the keys for a manufacturing process to receive approval. An appropriate manufacturing platform is therefore pivotal. The use of well-established, well-characterized, consistent, and scalable production processes when entering clinical development might shorten the approval time.
Based on a well-established integrated process platform and abundant technical experience, uBriGene has successfully completed the preclinical CMC process development and production of the LX101 project. In the past three years, uBriGene has established GMP factories in Jinan and Suzhou (China). As of now, uBriGene’s fermentation scales include 5L, 10L, 20L, 200L, 500L, and 2000L and are equipped with advanced purification technology, producing AAV virus titer as high as 1E14VG/L.
uBriGene has always been committed to technological innovation. In addition to the production of GMP AAV virus platforms, it has also developed related technology platforms including strain bank construction, cell bank construction, GMP plasmid, GMP lentivirus and CAR-T preparation, as well as quality testing platforms covering biochemistry, microorganisms, and chemistry, with each platform in complete physical isolation to avoid cross-contamination. uBriGene’s one-stop platform can fully meet customers' needs for early R&D, clinical trials, and large-scale commercial production. uBriGene’s development and innovation of core technologies ensures its market competitiveness and long-term prospects.
The Future
Studies have shown that AAV gene therapy has therapeutic potential for rare and genetic diseases caused by dominant mutations in the retina and other parts of the central nervous system. The approval of LX101 ophthalmic injection by CDE in China may suggest an accelerated trend for new gene therapy ophthalmic drugs to enter the Chinese market.