Johnson & Johnson's $415M Gene Therapy for X-Linked Retinitis Pigmentosa Fails Phase III Trial

Recently, according to foreign media reports, a gene therapy developed by Johnson & Johnson for the treatment of X-linked retinitis pigmentosa (XLRP), a hereditary vision degeneration disease, failed to meet the primary endpoint in Phase III clinical trials.

The therapy, named botaretigene sparoparvovec (shortened to bota-vec), aims to deliver the normal RPGR gene to retinal photoreceptor cells via a modified viral vector, thereby restoring the function of key visual proteins lost due to genetic mutations and slowing or halting the deterioration of patients' vision.

This Phase III trial enrolled a total of 95 patients who were randomly assigned to receive either a low dose, high dose, or delayed treatment. Although no statistically significant improvement was observed in the primary endpoint—the change in patients' ability to navigate a visual maze within one year—positive trends were noted in some secondary endpoints, such as functional vision and electroretinographic responses.

In terms of safety, all treated subjects reported at least one treatment-related adverse event, with approximately 70% experiencing ocular inflammation, most of which were mild or moderate. Additionally, 29 individuals in the treatment group developed cataract-related issues, compared to only 6 in the delayed treatment group. No deaths have been reported at this time.

Bota-vec was initially developed by gene therapy biotech company MeiraGTx. In 2019, Janssen, a subsidiary of Johnson & Johnson, entered into a collaboration with MeiraGTx and paid $100 million as an upfront fee. Subsequently, Johnson & Johnson made milestone payments in 2021 and 2023, eventually acquiring full development and commercialization rights for the therapy for a total of $1.3 billion. If the therapy successfully reaches the market in the future, MeiraGTx remains eligible to receive up to $285 million in additional payments.

Notably, there have been previous failed attempts by other pharmaceutical companies in the XLRP treatment field. For instance, Biogen terminated its project in 2021 after another gene therapy, cotoretigene toliparvovec, failed to meet the primary endpoint in a Phase II/III trial. Currently, Beacon Therapeutics is conducting a Phase II/III clinical trial for laru-zova. The company claims that its therapy can express the full-length RPGR protein, offering differentiation potential. Interim data released at the end of 2023 showed preliminary efficacy in improving vision under low-light conditions, with good tolerability. The trial is still recruiting participants.

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