Key Takeaways

  • Oculis has treated the first patient in PIONEER-1, the first of 2 registrational trials evaluating Privosegtor for acute-onset optic neuritis
  • The study's primary endpoint is the proportion of patients gaining at least 15 letters from baseline, with the primary analysis planned for month 3
  • Privosegtor has received FDA Breakthrough Therapy and EMA PRIME designations for optic neuritis, and Oculis is also planning to study the therapy in acute MS relapses

Oculis announced that the first patient has been treated in the PIONEER-1 registrational trial evaluating Privosegtor for acute-onset optic neuritis, marking the start of the company’s late-stage clinical program for the investigational neuroprotective therapy.

PIONEER-1 is the first of 2 registrational studies in Oculis’ PIONEER program, or "Privosegtor Investigation in Optic Neuropathies Efficacy Evaluation Research." The trial is enrolling a broad population of patients with acute-onset optic neuritis, including those with and without multiple sclerosis (MS).

“Treating the first patient in PIONEER-1 at a leading center in the US is a pivotal milestone as we advance our late-stage pipeline while focusing on neuro-ophthalmology,” Riad Sherif, MD, CEO of Oculis, said in a company statement.

Dr. Sherif added that, if successful, Privosegtor could address an unmet need for neuroprotection in optic neuropathies and potentially have applications in neurological conditions, including acute MS relapses.

Privosegtor is an investigational peptoid small molecule designed to cross the blood-brain and retinal barriers. Oculis is developing the agent as a potential neuroprotective treatment for optic neuritis, with the goal of preserving neural structures and visual function following acute disease.

The primary endpoint of PIONEER-1 is the proportion of patients achieving a gain of at least 15 letters from baseline. The secondary endpoint is mean change in low-contrast visual acuity at month 3. The primary analysis will take place at month 3, with patients followed through month 12 to evaluate long-term safety and tolerability.

According to Oculis, dosing and enrollment criteria in PIONEER-1 will closely resemble those used in the phase 2 ACUITY trial. In that study, Privosegtor produced improvements in low-contrast visual acuity at month 3 that persisted through month 6, along with anatomical and biological findings that the company said were consistent with neuroprotection compared with placebo.

Those findings supported the FDA's granting of Breakthrough Therapy designation and the European Medicines Agency's granting of Priority Medicines, or PRIME, designation to Privosegtor for optic neuritis.

Oculis also received written agreement from the FDA under a Special Protocol Assessment for PIONEER-1. According to the company, the agency agreed that the trial's design and planned analysis adequately address objectives necessary to support a potential new drug application for optic neuritis, provided the study is successful and subject to review of the complete NDA data package.

Oculis said it and its partners have established a multidisciplinary network involving emergency department physicians, ophthalmologists, and neurologists to identify and enroll eligible patients. The company said the approach is intended to streamline the pathway from patient identification to treatment and account for seasonal patterns in optic neuritis enrollment.

“For decades, our approach to optic neuritis and other acute MS attacks has stopped at trying to reduce the secondary acute inflammation, while preventing axonal and secondary neuronal loss has not been accomplished,” said Mark Kupersmith, MD, professor and vice chair of translational research and chair of NORDIC at the Icahn School of Medicine at Mount Sinai in New York. He added that positive findings from PIONEER-1 could provide insights into treating optic neuropathies and measuring structural central nervous system preservation in other neurodegenerative conditions.

Beyond optic neuritis, Oculis is preparing to investigate Privosegtor in acute MS relapses. The company said it plans to submit an investigational new drug application for that indication in the fourth quarter of 2026 following pre-IND feedback from the FDA's neurology division.