Targeting human retinal progenitor cell injections for retinitis pigmentosa

Reviewed by Dr David S. Boyer.

Although there are currently no options available to treat retinitis pigmentosa (RP), one novel approach has been evaluated in a Phase 2 clinical trial carried out in this patient population. The study determined the clinical effect of injecting human retinal progenitor cells to improve vision and visual fields by activating and preserving retinal cells.

According to Dr David S. Boyer, adjunct clinical professor of ophthalmology at the Keck School of Medicine of USC in Los Angeles, California, United States, the findings indicated that this treatment may be able to enhance vision and visual fields in specific patients with RP whose living cells can be rejuvenated.

Method and endpoints of the retinal progenitor cell injection trial

A heterogeneous group of patients with RP and 20/80 to 20/800 vision were included in the trial. Patients were not excluded based on their clinical picture or genetics. Following exclusion due to administration of the wrong dose, loss to follow-up or a pre-existing condition, 74 patients were included in the study and randomised 1:1:1 in the analysis.

The cells given by injection were regenerative and intended to enhance those that might still be living in the retina. Three study groups were tested: patients who received an injection of 3 million cells; patients who received an injection of 6 million cells; and a sham control group. The goals were to determine the ideal dose of cells and identify secondary endpoints, and to determine the clinical characteristics of the patients who might benefit most from one intravitreal dose in a Phase 3 trial.

The primary endpoint was the mean change in the best-corrected visual acuity (BCVA) from baseline to month 12. The secondary endpoints were low light mobility to facilitate navigation through a maze, kinetic visual fields that map the remaining vision, contrast sensitivity and the results of a visual functioning questionnaire (VFQ-48).

Evaluation of the clinical study results

Injection of the 6-million-cell dose produced a moderate improvement in vision of approximately 4.4 letters over the sham treatment. The kinetic visual field also showed an improvement, as did contrast sensitivity and results of the VFQ-48; however, Dr Boyer reported that no improvements were seen in the low luminance test.

In previous studies, Dr Boyer explained, it had not been possible to measure patients with a visual field of less than 12 degrees reliably, because of their inability to maintain fixation without central vision. Moreover, patients with a three-line difference in vision between the treated eye and the fellow eye also had a decrease in vision that could not be improved.

When the investigators evaluated the patients in the Phase 2 trial according to these specific parameters, they saw approximately 15 letters of improvement and significant improvements in the kinetic visual fields, contrast sensitivity, VFQ-48 and navigation through the low luminance maze when the patients in the 6-million-cell group and those who received the sham treatment were compared.

At the time of this article, approximately 130 eyes had been treated and the safety profile was excellent. No serious adverse events occurred in the group treated with the higher dose. “The study found that the 6-million-cell dose was the most effective, all clinical trial endpoints were useful and supportive of the treatment effect, the treatment had an excellent safety profile, and certain patients from the broad set of [patients with RP] studied can be assessed more reliably,” Dr Boyer said.

However, the question remains as to which patients would benefit the most from this treatment. Heat maps were generated that showed the width and the band of the ellipsoidal zone; the results indicated that its thickness may be predictive of improvements in the endpoints (BCVA, visual fields, contrast sensitivity, low luminance level in the maze and VFQ-48 results) with the human progenitor cell treatment compared with sham treatment. Similarly, the mean foveal central thickness was also highly correlated with improvements in the endpoints in the 6-million-cell group.

“The optical coherence tomography findings indicated structural predictors—i.e., the ellipsoidal zone thickness and the mean foveal thickness—for [participants] who received the 6-million-cell dose who were most likely to improve with injection of human progenitor cells,” Dr Boyer concluded.

“There was no evidence of structural improvement at 12 months. The potential minimal thickness should be considered as part of the inclusion criteria for future studies,” Dr Boyer added. The Phase 3 trial will begin in the third quarter of 2022.

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David S. Boyer, MD

E: vitdoc@aol.com

This article was adapted from Dr Boyer’s presentation at the Bascom Palmer Eye Institute’s Angiogenesis, Exudation, and Degeneration conference, held virtually in February. Dr Boyer is a consultant to jCyte, which ran and participated in the study under discussion.

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