Retinitis pigmentosa is a group of hereditary diseases of the eye that lead to progressive loss of vision due to cells in the retina becoming damaged and eventually dying.

Pre-clinical studies carried out in disease models by academic collaborators have demonstrated that, when transplanted into the retina, ReNeuron’s hRPC technology has the potential to preserve existing photoreceptors, potentially reducing or halting further deterioration of vision. In addition, these hRPC cells have been shown to mature into functional photoreceptors that are capable of becoming engrafted into the photoreceptor layer.

A Phase 1/2a clinical trial in RP subjects is currently ongoing in the US, UK and Spain with subject enrolment complete and subjects now being followed up in accordance with the protocol. This open-label, dose escalation study to evaluate the safety, tolerability and preliminary efficacy of a single, sub-retinal injection of the hRPC stem cell therapy candidate in patients with advanced RP,  was initially conducted at Massachusetts Eye and Ear Infirmary in Boston, and subsequently two further US sites were opened at Retinal Research Institute in Phoenix and Casey Eye Institute, Oregon  – and then more recently sites were opened in the UK and Spain – the Oxford Eye Hospital, with Professor Robert MacLaren as Principal Investigator and the Institut de la Màcula, Barcelona, with Dr Jordi Mones as Principal Investigator.

The primary endpoint of the study is safety, with patients being followed up for 24 months post-treatment, which includes measurements of visual acuity.  Expansion into the Phase 2a element of this study involved subjects with some retinal functionality, in contrast to the very poor vision and lack of potential for improvement of the subjects in the Phase 1.

In October 2019, positive interim efficacy data from patients treated in the initial Phase 2a segment of the study were announced by the Company and subsequently presented by Dr. Pravin Dugel at the American Academy of Ophthalmology Meeting in San Francisco.  The data showed a group of subjects who had had a successful surgical procedure with sustained clinically relevant improvements in visual acuity compared with baseline, as measured by the number of letters read on the ETDRS chart (the standardised eye chart used to measure visual acuity in clinical trials).

In June 2020 (and updated in November 2020), subsequent long-term efficacy data from this initial Phase 2a segment of the study continued to show a meaningful clinical effect from the therapy at all time points out to twelve months post-treatment.  The degree of efficacy observed varied between patients, with mean results as set out in the table below:

Months post-treatment Mean change from baseline in visual acuity in treated eye* Mean change from baseline in visual acuity in untreated eye* Difference in mean change between treated eye and untreated eye*
1 +7.9 letters (n=9) + 0.2 letters (n=9) + 7.7 letters  (n=9)
2 +8.0 letters (n=9) + 1.2 letters (n=9)   + 6.8 letters (n=9)
3 +10.8 letters (n=9) + 4.4 letters (n=9)   + 6.4 letters (n=9)
6 +9.6 letters (n=9) + 3.4 letters (n=9)   + 6.2 letters (n=9)
9 +7.1 letters (n=8) + 1.2 letters (n=8) + 5.9 letters (n=8)
12 +9.9 letters (n=7) – 3.2 letters  (n=7)   + 13.1 letters (n=7)

* In patients with a successful surgical procedure

An improvement of + 23 letters is equivalent to reading an additional four lines of letters on the ETDRS eye chart, the standardised eye chart used to measure visual acuity in clinical trials.  An improvement of at least + 15 letters from baseline on the ETDRS chart is considered to be clinically meaningful by the US Food and Drug Administration (FDA), as stated in their recent guidance on gene therapy for retinal disorders.  As a comparator, the difference between a patient with 20/20 vision and 20/200 vision (the latter being the legal definition for blindness in terms of central visual acuity) would be the equivalent of being able to read an extra ten lines on the ETDRS chart.

Following the initial Phase 2a segment of the study, the Company received regulatory approval to expand the Phase 2a study to treat up to a further nine RP subjects, at a higher 2 million cell dose, under an approved, revised study protocol. In June 2021 the Company announced that dosing was temporarily suspended. Following necessary approvals, the study was then reopened in the US, UK and Spain.

Seven subjects were treated under the revised approved study protocol. However, following a review of the latest data and a meeting of the Scientific Advisory Board the Company took the decision to out-license its programme assets following completion of the current clinical data package.

Although there had been no serious adverse events (SAEs) attributed to the drug itself, experience in treating the subjects at the 2 million cell dose showed that the surgical procedure required to deliver this higher dose (which involves a greater volume and therefore greater surgical complexity) led to more surgical complications compared to that seen with the 1 million cell dose. The data collected for this patient population, which was impacted by the SAEs and difficulty in deploying the 2 million cell dose, have to date shown very limited evidence of efficacy and given the SAEs, a number of patients saw a reduction in visual acuity in the treated eye.

Additionally, while data from the Initial Study showed at 12 months a mean 9.9 letter improvement versus baseline in ETDRS letter score, analysis of the 24-month data, while inconclusive, does appear to show that efficacy wanes after 12 months. Four out of nine patients still show a positive response versus baseline at month 24.

Even though certain patients did appear to benefit from the treatment (in particular in the first 12 months), further patients would need to be treated at the 1m dose to try to identify which sub-populations are most likely to lead to a higher and longer lasting response.

For an article published by the Foundation for Fighting Blindness regarding this trial click here..