Neuroprotective Agent Privosegtor Gains FDA Breakthrough Designation for Optic Neuritis

In recent news, Oculis’ privosegtor, a neuroprotective candidate, was granted breakthrough therapy designation by the FDA for the treatment of acute optic neuritis. The agent is currently being evaluated in a large-scale, registrational phase 3 program that includes 2 studies, PIONEER-1 and PIONEER-2.¹

Currently, there are no FDA-approved medications specific to treat optic neuritis, although there are some therapies approved for conditions like neuromyelitis optica spectrum disorder (NMOSD) that reduce relapse risk, including optic neuritis attacks. Privosegotor, which is also being tested in patients with non-anteritic anterior ischemic optic neuropathy (NAION), is a novel peptoid small molecule candidate with the potential to become the first neuroprotective therapy for neuro-opthalmic diseases.

For clinical trials, PIONEER-1 initiated in late 2025, and PIONEER-2 is expected to kickoff in the first half of 2026. These studies, which use change in low-contrast visual acuity (LCVA) at 3 months as the primary end point, consist of a broad patient population, including those with multiple sclerosis (MS) and those without MS. In addition, the agent is currently being tested in another study, PIONEER-3, which uses patients with NAION and shares the same core design and operational elements as PIONEER-1 and PIONEER-2.²

“Today’s Breakthrough Therapy Designation underscores Privosegtor’s significant potential as a first‑of‑its‑kind neuroprotective therapy for people living with optic neuritis, and highlights our commitment to redefining what’s possible for patients suffering from neuroaxonal loss,” Riad Sherif, MD, chief executive officer at Oculis, said in a statement.¹ “With the ACUITY results and Privosegtor now progressing as a neuroprotective platform across key neuro‑ophthalmic diseases, Oculis is uniquely positioned to reshape the treatment landscape in areas with substantial unmet needs, and 2026 is shaping up to be a milestone‑rich year across our late‑stage portfolio.”

READ MORE: FDA Approves Generic Glatiramer Acetate Injection for Multiple Sclerosis Treatment

Prior to the PIONEER studies, privosegtor showed promise in the phase 2 ACUITY trial (NCT04762017), a randomized, double-masked, placebo-controlled study. The trial tested privosegtor (2 or 3 mg/kg intravenous [IV] daily for 5 days) as an add-on to standard of care (methylprednisolone IV) in patients with acute optic neuritis, excluding those with aquaporin-4 (AQP4) positivity. ACUITY used cardiac safety as the primary end point, with key secondary outcomes that included changes in ganglion cell/inner plexiform layer (GCIPL) thickness, retinal nerve fiber layer (RNFL) thickness, and 2.5% LCVA.

In ACUITY, 33 of the 36 patients were available for the modified intention to treat analysis. All told, results revealed that treatment with privosegtor 3 mg/kg/day led to a 43% reduction vs placebo on GCIPL thinning at month 3 (least square [LS] mean difference, 9.2 [SE, 5.4] µm; 90% CI, 0.0-18.3) and Month 6 (9.1 [SE, 5.4] µm; 90% CI, 0.1-18.2, respectively). In addition, RNFL thinning showed reductions of 28% at month 3 (LS mean difference, 11.1 [SE, 6.2] µm; 90% CI, 0.4-21.9) and 30% reduction at Month 6 (12.7 [SE, 6.4] µm; 90% CI, 1.5-23.9, respectively).³

Coming into ACUITY, patients had a mean disease duration of 9.8 (±2.5) days, with 61% of the cohort having MS. Overall, differences to placebo in LCVA improvement and nominal two-sided P-values were 18.2 (SE, 5.7) letters at month 3 (90% CI, 8.4-27.9; P = .004), and 14.8 (SE, 5.5) letters at month 6 (90% CI, 5.4-24.1; P = .012). Importantly, there were no between-group differences in adverse events (AEs), as well as no drug-related serious AEs recorded in the trial.

"The ACUITY trial delivered truly groundbreaking results, demonstrating for the first time in a single study that a drug candidate consistently improves visual function alongside anatomical and biological evidence of neuroprotective benefit,” Mark Kupersmith, MD, chief medical advisor, Neuro-Ophthalmology, Oculus, said in a statement.¹ “Significant unmet medical needs remain, as patients with optic neuritis—more often young women and frequently experiencing the first sign of multiple sclerosis—are still at high risk of permanent visual loss.”

REFERENCES
1. Oculis Announces U.S. FDA Breakthrough Therapy Designation Granted to Privosegtor for Treatment of Optic Neuritis. News release. January 6, 2026. Accessed January 9, 2026. https://investors.oculis.com/news-releases/news-release-details/oculis-announces-us-fda-breakthrough-therapy-designation-granted
2. Oculis Accelerates Privosegtor into Registrational Trials in Acute Optic Neuritis, Pioneering the Path for a Potential First-in-class Neuroprotective Therapy. News release. Oculis. October 6, 2025. Accessed January 9, 2026. https://investors.oculis.com/news-releases/news-release-details/oculis-accelerates-privosegtor-registrational-trials-acute-optic
3. Louapre C, Bonnin S, Mariani LL, et al. Reduction in Retinal Ganglion Cell Loss and Improved Low Contrast Visual Acuity with Privosegtor in Acute Optic Neuritis: Results from a Multicenter Randomized Placebo-Controlled Double-Masked Trial.