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Oculis Holding AG, a global biopharmaceutical company focused on breakthrough innovations to address significant unmet medical needs in ophthalmology and neuro-ophthalmology, announced that it has received written agreement from the US Food and Drug Administration (FDA) under a Special Protocol Assessment (SPA) regarding PIONEER-1, the first registrational trial within the PIONEER Programme evaluating Privosegtor for the treatment of optic neuritis (ON). This formal FDA agreement confirms the design and planned analysis of the PIONEER-1 study are adequate to address the objectives necessary to support a future NDA submission, subject to a successful trial outcome and FDA review of the complete submission.
Privosegtor is a novel peptoid small molecule that crosses the blood-brain and retinal barriers; it has the potential to become the first neuroprotective therapy for ON, with broad applicability in other neuro-ophthalmic and neurological diseases. Following the successful phase 2 ACUITY trial, Oculis launched the PIONEER programme which includes two pivotal trials to support registrational plans for Privosegtor in ON.
The PIONEER-1 phase 3 study will evaluate Privosegtor in patients with ON across a broad population, including those with and without multiple sclerosis (MS). The primary endpoint is defined as the proportion of patients achieving at least a 15-letter gain from baseline in low-contrast visual acuity (LCVA) at Month 3, a well-established endpoint for clinically meaningful visual function in ophthalmology trials. Patients will be followed for 12 months to assess Privosegtor’s long-term safety and tolerability. Dosing and patient enrollment criteria will closely mirror those of the phase 2 ACUITY trial, in which Privosegtor + steroid showed substantial improvements in vision at Month 3, which persisted through Month 6, as measured by LCVA, along with consistent anatomical and biological neuroprotective benefits compared with placebo + steroid. The most common drug-related adverse events (AEs) were headache and acne (each in two participants; 10.5%). No drug-related serious AEs or AEs leading to treatment or study discontinuations occurred. These positive findings supported the granting of Breakthrough Therapy designation by the US FDA and Priority Medicines (PRIME) designation by the European Medicines Agency (EMA) for the treatment of ON.
Riad Sherif, M.D., chief executive officer of Oculis, remarked, “The FDA SPA agreement for the PIONEER-1 trial, following Breakthrough Therapy and PRIME designations from the FDA and EMA, clarifies our path to NDA and validates our scientific approach. With a potential $7 billion US market in acute optic neuropathies, Privosegtor aims to address a critical gap in neuroprotection in neuro-ophthalmology and beyond.”
Mark Kupersmith, M.D., chief medical advisor, Neuro-ophthalmology and professor, vice chair translational research, Chair NORDIC at Icahn School of Medicine at Mount Sinai Hospital, New York, added: “Privosegtor has demonstrated compelling results in the treatment of optic neuritis with improvement of visual function combined with positive anatomical and biological measures of nerve cell preservation. The consistency of the results observed for all three determinations provides hope for patients suffering from optic neuropathies, many of whom have permanent visual deficits. I think this new therapy has the potential to bridge the gap from the lab to patients for neuroprotection in ophthalmology and neurology. I look forward to continuing our collaborative work with Oculis to further advance this promising candidate through late-stage clinical development.”
Privosegtor, a novel peptoid small-molecule candidate that crosses the blood-brain and retinal barriers, has the potential to become the first neuroprotective therapy for optic neuritis (ON) and other neuro-ophthalmic diseases. Positive results from the ACUITY phase 2 trial demonstrated Privosegtor’s neuroprotective potential through anatomical preservation of the retina and improvements in visual function after an acute episode of optic neuritis. Consistent results were observed in animal models of neuroinflammation and neurodegeneration, where Privosegtor preserved retinal ganglion cell damage and was associated with improvements in mobility (clinical function disability). Privosegtor has received Breakthrough Therapy designation from the FDA and Priority Medicines (PRIME) designation by the European Medicines Agency (EMA) as well as Orphan Drug from both the FDA and the EMA for ON. Privosegtor is currently being evaluated in Oculis’ PIONEER (Privosegtor Investigation in Optic Neuropathies Efficacy Evaluation Research) programme which includes two registrational trials in ON and one registrational trial in non-arteritic anterior ischemic optic neuropathy (NAION). In addition to its potential neuroprotective effect on the optic nerve, Privosegtor could also have wide applicability in treating other neuro-ophthalmic and neurological indications.
Privosegtor is an investigational drug and has not received regulatory approval for commercial use in any country.
Optic Neuritis (ON) is a rare condition characterized by an acute inflammation of the optic nerve that can lead to permanent visual impairment. It affects up to 8 in 100,000 people worldwide with a US annual incidence estimated to be >30,000 and often represents the first sign of multiple sclerosis. It mainly occurs in adults between the age of 20 and 40 years and is more frequent in women (2:1). ON is a type of neuropathy (nerve disease) that happens when acute inflammation of the optic nerve affects the signals traveling from the eyes through the brain, causing pain, vision loss and other symptoms. The cells that make up the optic nerve have a lipid protective coating called a myelin sheath, which is preferentially damaged in ON. Without myelin, the optic nerve cells can’t send signals properly and axons can be irreversibly lost. To date there is no specific therapy approved for acute optic neuritis and the unmet needs remain for therapies that can prevent vision loss after an acute episode by reducing nerve cell permanent damage or death.
Non-arteritic anterior ischemic optic neuropathy (NAION) is an acute optic nerve disorder that causes permanent visual impairment in >60% of affected patients. It is the most common cause of acute optic nerve injury in individuals over 50 years old4 and affects up to 10.2 per 100,000 people worldwide with a US annual incidence estimated to be >30,000. In NAION, the optic nerve head region swells and there is painless sudden vision loss. The swelling eventually resolves, but the optic nerve axons and neuronal cell bodies (in the retina) are permanently lost, leading to significant irreversible visual impairment or even blindness. There are no approved therapies for NAION and the unmet medical need is for therapies that preserve vision and provide neuroprotection for patients suffering from NAION.
A Special Protocol Assessment (SPA) is a written agreement between a sponsor and the US Food and Drug Administration (FDA) regarding the design, endpoints, and planned statistical analyses of a clinical trial intended to support a marketing application. SPAs are intended to document FDA’s agreement that the proposed trial design is adequate to support regulatory approval, provided the study is conducted as agreed and achieves its prespecified objectives. SPA agreement is generally sought for pivotal phase 3 registrational trials intended to form a primary basis of evidence of effectiveness. SPA agreement provides greater regulatory clarity and predictability for drug development programs, but does not guarantee approval of a marketing application, which remains subject to the successful completion of the trial, submission of all required data, and FDA review.
Oculis is a global biopharmaceutical company focused on breakthrough innovations to address significant unmet medical needs in neuro-ophthalmology and ophthalmology.
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