Elad Kedar is the CEO of Orasis Pharmaceuticals, an emerging ophthalmic pharmaceutical company with locations in Ponte Vedra, Fla., and Herzliya, Israel. The company is developing CSF-1, a corrective eyedrop to improve near vision for people with presbyopia. Mr. Kedar has more than 20 years of executive experience in the pharmaceutical industry developing, scaling and commercializing health-care organizations. He previously held executive positions in Eli Lilly and PharmaSwiss.

Ophthalmology Management: Orasis Pharmaceuticals’ lead candidate is the novel presbyopia corrective eyedrop, CSF-1 (low dose pilocarpine hydrochloride 0.4%). How does it work?

Elad Kedar: CSF-1 is a proprietary, preservative-free formulation of low-dose pilocarpine and multi-faceted vehicle that is being investigated for the treatment of presbyopia. CSF-1 improves near visual acuity and works by constricting the pupil, creating a “pinhole effect” similar to that of a camera, therefore increasing depth of focus.

Early on, we recognized there was an opportunity to address an unmet need of providing an alternative to reading glasses for presbyopic patients. We realized that in order to have a successful alternative to readers, we needed an optimal balance of efficacy, safety and comfort. Identifying the minimal effective concentration of 0.4% was critical, as we understood the historical challenges with higher concentration miotics (used primarily to treat glaucoma). In addition, we optimized our preservative-free formulation at a near-neutral pH along with a multi-faceted vehicle to assist with comfort.

OM: Phase 3 NEAR-1 and NEAR-2 clinical trials of CSF-1 met primary and key secondary endpoints. Can you give us an overview?

EK: Consistent with our Phase 2b results, our Phase 3 studies (NEAR-1 and NEAR-2) met their primary and key secondary endpoints on Day 8, achieving statistically significant 3-line or more gain in distance-corrected near visual acuity with no loss of 1-line or more in distance visual acuity. Pooled across the two studies, CSF-1 achieved statistically significant results at all efficacy time points measured — including 20 minutes out to 8 hours on Day 15.

We’ve also spent time analyzing additional endpoints such as 2-line improvement, which could be appropriate for early presbyopes, along with functional vision at 20/40 near (J3). CSF-1 also demonstrated favorable comfort scores (using formal comfort assessment) and essentially no changes in eye redness.

More pooled results were presented at the ASCRS annual meeting. Dr. Preeya Gupta noted that over 2/3 of patients experienced clinically meaningful results of 2 lines or better over the treatment period of 8 hours, and a 2-line gain or better was comparable to achieving functional near vision of 20/40 or better in early to moderate presbyopes. Additionally, Dr. Marjan Farid discussed the 3-line results of NEAR-1 and NEAR-2 that showed a significantly greater percentage of participants who received CSF-1 gained ≥3 lines from baseline across all timepoints on Days 8 and 15 without compromising distance vision.

In February 2023, the FDA accepted Orasis’ new drug application for CSF-1 and assigned a Prescription Drug User Fee Act goal date of Oct. 22, 2023.

OM: Explain what Orasis Pharmaceuticals can do to help ophthalmologists and their patients with unmet needs.

EK: Based on extensive market research with thousands of patients, we learned that many presbyopes (especially early presbyopes) are seeking alternatives to readers. These are people who desire less dependence on them during a normal working day or would like a break for a social activity or hobby. They value flexibility so they can manage their ‘new near’ on their terms. CSF-1 provides flexibility for the patient because it can be dosed up to twice a day at any time. We looked at efficacy after one drop along with efficacy out to 8 hours when taking the second dose 3 hours after the first. The ability to take a second dose, when desired, is a valued attribute of our product based on recent market research.

We feel CSF-1 will provide an excellent addition to what eye-care providers are recommending today, giving patients an alternative when they want a break from readers. OM