Abstract Details

Title Treatment Effect of Idebenone in Leber Hereditary Optic Neuropathy Using an Alternate Threshold of Clinically Relevant Visual Acuity Change

Topic Neuro-ophthalmology/Neuro-otology

Presentation(s) S18 - Neuro-ophthalmology/Neuro-otology (3:42 PM-3:54 PM)

Poster/Presentation
Number 002

Objective

To re-assess LEROS visual acuity (VA) outcomes using the stricter FDA-recommended threshold for clinically relevant VA change (±0.3 logMAR).

Background

LEROS, a phase IV, open-label, natural-history (NH) controlled study (NCT02774005), improved VA outcomes with idebenone for patients with Leber hereditary optic neuropathy over 2 years, although response varied by disease phase and mitochondrial DNA (mtDNA) mutation.

Design/Methods

Idebenone-treated and matched NH eyes were assessed for clinically relevant benefit (CRB), recovery (CRR), and worsening (CRW) at 12 months. Clinically relevant VA change was defined as ±0.3, rather than ±0.2 logMAR. Eyes were stratified by time since onset at baseline: subacute/dynamic (≤1 year) and chronic (>1 year), and by mtDNA mutation: m.11778G>A, m.3460G>A, m.14484T>C.

Results

In the subacute/dynamic phase, a significantly higher CRB rate (36.6% [n=52/142] vs 20.7% [n=40/193], p=0.039, odds ratio [OR] 1.75), and significantly lower CRW rate (23.1% [n=27/117] vs 53.1% [n=69/130], p<0.001, OR 0.31) was observed for idebenone-treated versus matched NH eyes, respectively. CRR was observed in 26.1% (n=37/142) of idebenone-treated versus 17.6% (n=34/193) of matched NH eyes (p=0.538, OR 1.20).

In the chronic phase, a significantly higher CRB (46.2% [n=66/143] vs 36.6% [n=56/153], p=0.031, OR 1.71) and CRR rate (26.6% [n=38/143] vs 16.3% [n=25/153], p=0.016, OR 2.03), and a significantly lower CRW rate (3.1% [n=3/96] vs 12.4% [n=11/89], p=0.010, OR 0.20) was observed for idebenone-treated versus matched NH eyes, respectively. Overall, VA outcomes by disease phase were similar to previous analyses using ±0.2 logMAR.

VA outcomes assessed by mtDNA mutation showed similar trends to those in previous analyses using ±0.2 logMAR. However, there were differences in the magnitude of CRR/CRW (treated vs NH) observed in some cases.

Conclusions

Using the stricter FDA-recommended threshold for clinically relevant VA change to re-assess the LEROS data, idebenone treatment still improved outcomes in many cases. However, treatment effect varied by disease phase and mtDNA mutation.

Authors/Disclosures
Prem S. Subramanian PRESENTER	The institution of Dr. Subramanian has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Tourmaline Bio. The institution of Dr. Subramanian has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Amgen. The institution of Dr. Subramanian has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alumis. The institution of Dr. Subramanian has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genentech. The institution of Dr. Subramanian has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Kriya Therapeutics. The institution of Dr. Subramanian has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Viridian Therapeutics. The institution of Dr. Subramanian has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Dompé. The institution of Dr. Subramanian has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for argenx. The institution of Dr. Subramanian has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Chiesi. Dr. Subramanian has received personal compensation in the range of $10,000-$49,999 for serving as an officer or member of the Board of Directors for American Academy of Ophthalmology. Dr. Subramanian has received personal compensation in the range of $10,000-$49,999 for serving as an Expert Witness for various law firms. The institution of Dr. Subramanian has received research support from Amgen. The institution of Dr. Subramanian has received research support from NIH. The institution of Dr. Subramanian has received research support from US Department of Defense. The institution of Dr. Subramanian has received research support from Immunovant. The institution of Dr. Subramanian has received research support from Tourmaline Bio. The institution of Dr. Subramanian has received research support from Viridian Therapeutics. The institution of Dr. Subramanian has received research support from Neurophth. The institution of Dr. Subramanian has received research support from GenSight Biologics. Dr. Subramanian has received intellectual property interests from a discovery or technology relating to health care. Dr. Subramanian has received publishing royalties from a publication relating to health care. Dr. Subramanian has a non-compensated relationship as a President with North American Neuro-Ophthalmology Society that is relevant to AAN interests or activities. Dr. Subramanian has a non-compensated relationship as a Board Chair with North American Neuro-Ophthalmology Society that is relevant to AAN interests or activities.
Patrick Yu-Wai-Man	Patrick Yu-Wai-Man has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for GenSight Biologics. Patrick Yu-Wai-Man has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Chiesi. Patrick Yu-Wai-Man has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Stoke Therapeutics. Patrick Yu-Wai-Man has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for PYC Therapeutics.
Valerio Carelli, MD, PhD (University of Bologna)	Dr. Carelli has received personal compensation in the range of $0-$499 for serving as a Consultant for Chiesi Farmaceutici. Dr. Carelli has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Chiesi Farmaceutici.
Xavier Llòria (Chiesi SpA)	Xavier Llòria has received personal compensation for serving as an employee of Chiesi Pharmaceutici.
Thomas H. Klopstock, MD (University of Munich, Dept. of Neurology)	Dr. Klopstock has received personal compensation in the range of $500-$4,999 for serving as a Consultant for GenSight Biologics. Dr. Klopstock has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Chiesi GmbH. Dr. Klopstock has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Chiesi GmbH. Dr. Klopstock has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Chiesi GmbH. Dr. Klopstock has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for GenSight Biologics.

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