12.12.18

GenSight Biologics Reports Sustained Quality of Life Improvements at Week 72 of Phase 3 REVERSE Clinical Trial

Source: GenSight Biologics

GenSight Biologics reported that week 72 analyses of the data from its phase 3 REVERSE clinical trial revealed a sustained improvement in composite scores and selected sub-scores of a questionnaire used to measure patient perceptions of vision-related quality of life and ability to carry out daily activities impacted by loss of visual acuity.

The REVERSE trial evaluates the safety and efficacy of a single intravitreal injection of GS010 (rAAV2/2-ND4) in 37 subjects whose visual loss due to 11778-ND4 Leber Hereditary Optic Neuropathy (LHON) commenced between 6 and 12 months prior to study treatment.

All 37 patients in REVERSE were asked to complete the National Eye Institute Visual Function Questionnaire-25 (NEI VFQ-25), a reliable and valid vision-specific quality-of-life instrument that measures patients’ perception of their ability to perform daily activities requiring high-acuity vision and their general sense of well-being. The test defines sub-scales for functions such as near-distance vision and vision-related dependency as well as measures of well-being such as ocular pain and vision-related mental health. These sub-scale scores are aggregated into a composite score, excluding the general health rating question.

Well-accepted as a source of patient-reported measures of vision-related function, the questionnaire has been used in many clinical trials. A study in neovascular AMD – which, like LHON, leads to loss of central vision – showed that a clinically meaningful 15-letter change in BCVA was associated with a 4- to 6-point change in the NEI VFQ-25 composite score and in sub-scores in three pre-specified areas (near activities, distance activities, and vision-specific dependency).

At week 72, REVERSE patients reported mean improvement from baseline for NEI VFQ-25 scores in domains important to patients with loss of central vision: near activities, distance activities, vision-specific dependency and composite score. An improvement had already been observed at week 48, confirming sustained enhancement of ability to perform activities of daily living. In addition, large improvements were also noted in other domains relevant to LHON patients: role difficulties, general vision, and overall mental health. Again, the improvements observed at week 48 were sustained at week 72. The relevant comparison in REVERSE is against patients’ own baseline, because the NEI VFQ-25 is assessed by patient; by design, all REVERSE patients received an injection in one eye.

                               

NEI VFQ-25 Results from REVERSE

 

Mean change from baseline (absolute score and percent)

 
                               
   

Composite
Score**

 

Near
Activities

 

Distance
Activities

  Dependency  

Role
Difficulties

 

General
Vision

 

Mental
Health

 
Week 48   +7.2

23.2%

  +10.4

65.1%

  +9.6

49.8%

  +12.4

100.6%

  +14.5

65.0%

  +10.3

50.9%

  +11.2

81.9%

 
Week 72   +8.1

25.2%

  +9.5

58.1%

  +8.2

42.5%

  +18.9

130.2%

  +15.2

70.9%

  +11.9

54.1%

  +15.2

105.6%

 

Clinically
relevant
difference*

 

+3.90 to
+4.34

 

+4.67 to
+6.06

 

+5.15 to
+5.38

 

+4.72 to
+4.98

 

+3.31 to
+4.70

 

+4.38 to
+4.82

 

+4.70 to
+4.88

 

*Suñer et al. (2009): clinically relevant score differences based on a clinically significant 15-letter BCVA improvement at 12 months.

 

**The composite score is an average of the vision-targeted sub-scale scores, excluding the general health rating question.

 
                               

Improvement from baseline at Week 72 for other sub-scales: social functioning: +2.4 (23.3%); ocular pain: +1.4 (5.6%); color vision: +5.6 (20.8%); peripheral vision: +1.4 (15.5%). Missing values for general health subscale. Driving questions not pertinent to LHON patients.

“It is heartening and exciting to see the NEI VFQ-25 corroborate the effects that have been demonstrated by GS010: relative protection of retinal ganglion cells and their axons, as well as visual function improvement,” Bernard Gilly, Co-founder and Chief Executive Officer of GenSight, said in a company news release. “This tells us that clinical measurements obtained by our investigators add up to patients feeling that they can function better in day-to-day activities.”

“In the final analysis, improvement in quality of life measures is perhaps the most compelling metric of therapeutic intervention,” Mark Moster, MD, Neuro-Ophthalmology, Wills Eye Hospital; Professor of Neurology and Ophthalmology at Thomas Jefferson University, Philadelphia, PA; and Principal Investigator in the REVERSE, RESCUE, and REFLECT trials, said in the news release. “Although it is important for clinicians to find objective improvements in specific visual functions, it is even more important that we improve the quality of life of our patients rather than any one objective measure of vision. These results offer demonstration of that successful outcome.”

As per protocol, REVERSE subjects will be evaluated again at 96 weeks, and data will be reported in the second quarter of 2019.

Topline 48-week data for RESCUE, the second phase 3 clinical trial of GS010 in the treatment of LHON, is expected in early Q1 2019.

Reference cited: Suñer et al., Invest Ophthalmol Vis Sci. 2009;50:3629–3635. DOI:10.1167/iovs.08-3225

 

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