2026 American Academy of Neurology Abstract Website

Pablo Villoslada¹, Celine Louapre², Sophie Bonnin³, Louise-Laure Mariani², Mikael Cohen⁴, Caroline Froment⁵, Mark Kupersmith⁶, Leonard A Levin⁷, Sabri Markabi⁸, Caroline Papeix², Valérie Touitou², Rossella Medori⁹, Marion R. Munk¹⁰, Martin S. Zinkernagel¹⁰, Sebastian Wolf¹⁰
¹Neurology, Hospital del Mar Research Institute, ²Neurology, ³Ophthalmology, Hôpital Pitié Salpêtrière, APHP, ⁴Neurology, Hopital Pasteur, ⁵Neuro-Opthalmology, Hopital Neurologique Et Neurochirurgical P Wertheimer, ⁶Neuro-Ophthalmology, Icahn School of Medicine At Mount Sinai, ⁷Ophthalmology, McGill University, ⁸Health R&D LLC, ⁹Prexton Therapeutics SA, ¹⁰Ophthalmology, University Hospital Bern

Objective:

To evaluate the efficacy, safety, and tolerability of privosegtor in acute optic neuritis (AON).

Background:

Privosegtor (OCS-05), a peptoid small molecule with neuroprotective activity, is being studied as a treatment for AON.

Design/Methods:

The ACUITY phase 2 multi-center, randomized, double-masked, placebo-controlled study evaluated privosegtor (2 or 3 mg/kg IV daily for 5 days) as an addition to methylprednisolone IV in patients with AON of less than 12 days duration, excluding AQP4+ patients. The primary endpoint was safety. Key secondary endpoints included changes in 2.5% low contrast visual acuity (LCVA), ganglion cell/inner plexiform layer (GCIPL) thickness, and retinal nerve fiber layer (RNFL) thickness. The exploratory endpoint measured changes in plasma neurofilament-light (NfL) levels. Efficacy analyses used a Mixed Model for Repeated Measures to estimate least-squares mean change from baseline, with 90% confidence intervals and nominal two-sided p-values.

Results:

Thirty-three randomized participants were included in the modified intention-to-treat analysis, with balanced baseline characteristics. Improvement in LCVA compared to placebo with privosegtor 3 mg/kg/day was 18.2 (5.7) letters at Month 3 (90% CI: 8.4, 27.9, P=0.004), and 14.8 (5.5) letters at Month 6 (90% CI: 5.4, 24.1, P=0.012). There was a 43% reduction in GCIPL thinning compared with placebo at Months 3 and 6. RNFL thinning showed reductions of 28% at Month 3 and 30% at Month 6. Mean plasma NfL concentrations remained stable from baseline (6.6 µg/ml) to Month 1 (7.6 µg/ml) and Month 6 (5.8 µg/ml) with privosegtor. The placebo group showed a significant increase from baseline (8.6 µg/ml) at Month 1 (14.6 µg/ml), followed by a steady decline to Month 6 (9.3 µg/ml). Adverse events showed no differences in incidence between groups, with no drug-related serious adverse events.

Conclusions:

Privosegtor demonstrated significant improvement in visual function, reduced retinal ganglion cell damage, and lowered NfL changes, suggesting neuroaxonal preservation. The drug was well-tolerated by participants.