Johnson & Johnson gene therapy update – What happens now?
The latest research news from Retina UK.
Johnson & Johnson’s (J&J) experimental gene therapy for X-linked Retinitis Pigmentosa (RP), bota-vec, is currently under the microscope – but not in the way you might think! Despite previous positive findings causing excitement within the Inherited Retinal Dystrophy (IRD) community, progress has seemingly come to an abrupt halt, whilst we wait to hear the outcome of key decisions. Given the reported failure to reach the target primary endpoint in bota-vec’s phase 3 clinical trial, it remains unclear where J&J will go from here, with no clear development plan or regulatory steps announced as of early July 2025.
What is bota-vec?
Bota-vec, developed by J&J and MeiraGTx, is a new gene therapy for X-Linked RP, associated with mutations in the RGPR gene. RGPR is crucial for the healthy function of the light-sensing photoreceptor cells in the retina. As the gene is on the X chromosome, X-linked RP mainly affects males, with females being carriers or experiencing milder symptoms. You can find out more about X-linked inheritance at x-linked inheritance – Retina UK . The main symptoms of X-linked RP include night blindness, followed by progressive vision loss starting peripherally.
Bota-vec is a type of adeno-associated viral vector (AVV) gene therapy. This means that a harmless virus is used to package and deliver a healthy version of the RGPR gene to photoreceptor cells. This gene will then enable the production of a functional copy of the RGPR protein.
The results of the phase 1 and 2 clinical trials were encouraging, however, the LUMEOS phase 3 trial has reportedly failed to meet its primary endpoint.
What does this mean?
The conclusion about whether a treatment is effective is based on a clinical trial achieving a primary endpoint. This refers to the main question or result that is being measured. It is set before the trial begins and everything is planned around this.
The primary endpoint of the LUMEOS phase 3 trial was an improvement in a “vision-guided mobility assessment” (VGMA). This means that participants who received the gene therapy would need to show an improvement in navigating a maze in low light compared to their baseline attempt and participants in the control group. The maze was specifically designed for this study, although a similar test was used in the pivotal Luxturna study for the RPE65 gene therapy.
Findings of Phase 3 LUMEOS Trial:
- The group that received the gene therapy experienced a 13.4% greater improvement on the VGMA test at one year compared to the control group. This is described as ‘directionally supportive’ but not statistically significant.
- Multiple secondary endpoints showed clinically meaningful improvements – including low luminance questionnaire of patient reported outcomes, multiple retinal sensitivity metrics and low luminance visual acuity.
- 45% of patients who received the gene therapy could read at least two more lines of letters on the eye chart compared to 7% of control group participants.
- In an analysis of patients compared to controls – 40% of patients showed meaningful improvement in at least 2 of the 3 domains (functional vision, retinal function, visual function); whilst 0% showed improvements in controls.
Whilst the outcomes of the primary endpoint were described by J&J as ‘directionally supportive,’ the result was not statistically significant, and the data was described as ‘noisy’ by researchers. As such, the LUMEOS clinical trial was widely reported by industry press to have failed, despite the positive findings in secondary measures. However, J&J have not yet decided whether they will enter into discussions with regulators about licensing bota-vec or if this is the end of the road.
A statement from a J&J representative reads:
“We’re working to understand the totality of the data, inclusive of the clinical relevance of improvement shown on the majority of secondary endpoints. We remain engaged with the advocacy and research community and greatly appreciate their continued support as we work to determine next steps.” – ENDPOINTS News
The concern over the suitability of endpoints in rare disease clinical trials is not a new phenomenon. It is commonly acknowledged that due to the rare nature of such conditions, trial endpoints are difficult to design and often lack suitability, which in turn can significantly affect promising new treatments. Like with many other clinical trials within the IRD space, the question left for J&J to answer from this data is whether this is a failed trial, or a failed treatment.
As the community awaits an update on J&J’s next move, it is encouraging to see Beacon Therapeutics progressing through clinical trials for their laru-zova gene therapy for X-linked RP, with a notably different primary endpoint.
Beacon therapeutics are currently underway with VISTA, a phase 2/3 pivotal trial for a RGPR gene therapy. Preliminary trials have shown laru-zova to be generally safe and well-tolerated, with a high-dose being more effective. The VISTA trial is pivotal for gaining marketing approval, with the primary endpoint being a 15-letter improvement from baseline in low luminance visual acuity.
Whilst we acknowledge the frustration caused by the uncertainty in how treatments will move forward, it is encouraging to see positive preliminary results in a variety of clinical trials. We welcome an update from J&J as to how they plan to move forward and remain excited about the results from the Beacon Therapeutics trial expected in 2026.