X-Linked Retinitis Pigmentosa Investigative Gene Therapy is Looking Promising

Janssen Pharmaceuticals has an ongoing Phase 1/2 clinical trial for the inherited retinal disease X-linked retinitis pigmentosa (XLRP). They are investigating an adeno-associated gene therapy called RPGR as a therapeutic option for this rare disease which currently has no approved therapy.


RPGR gene therapy has received the following designations-

  • PRIME Designation from the EMA
  • Advanced Therapy Medicinal Product Designation from the EMA
  • Fast Track Designation from the FDA
  • Orphan Drug Designation from the FDA & EMA

Phase 1/2 Trial

The clinical trial is an open-label, dose-escalation investigation which is taking place at multiple trial centers in both the US and the UK. Participants were all at least 5 years of age or older and had been diagnosed with XLRP caused by RPGR mutations.

The primary endpoint of the trial is safety as well as tolerability of the AAV-RPGR therapy. Secondary endpoints include-

  • Retinal sensitivity
  • Visual function
  • Quality of life indicators

The trial is taking place in three phases.

  1. Dose-escalation
  2. Dose-confirmation
  3. Dose-expansion

The results from the first phase were very promising. 10 patients were given one of three dose levels of the therapy. At the 6 month mark, the 3 patients who had been given a low dose of the therapy and the 4 patients who had been given an intermediate dose had significant improvements in their retinal sensitivity by various measures. The researchers used a microperimetry and static perimetry approach as well as a pointwise comparison, V30, and mean retinal sensitivity measure. Perimetry measures are used as the standard-of-care measure to determine retinal function and sensitivity. Essentially, this measure helps to track disease progression.

For two patients in the highest dose group (out of three), inflammation was documented. Additionally, the vision of the patients in this group was not improved. For patients in the other two groups, safety information was as expected, with the most serious AE being related to the procedure, and resolved on its own. The procedure for administering the therapy is a sub retinal injection to the central retina. For every patient in the trial one eye received the therapy and the other eye was treated as the control.  

In sum, the first part of this trial has shown that low and intermediate dose levels of this gene therapy could have very promising outcomes for XLRP patients. This therapy could not just preserve the patient’s current vision, but improve the vision of these patients for good.

You can read more about this trial here.

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