CSF-1 Phase 2B clinical trials for presbyopia met primary and secondary endpoints

CSF-1 ophthalmic solution (pilocarpine hydrochloride 0.4%, Orasis Pharmaceuticals), a presbyopia eye drop candidate, met the primary safety and efficacy endpoints in the first of 2 phase 2b studies, and Marjan Farid, MD, ABO, discussed the results during a presentation at the American Society of Cataract and Refractive Surgery’s2022 annual meeting in Washington, D.C.

Farid is clinical professor of ophthalmology, and director, Cornea, Cataract and Refractive Surgery, Ocular Surface Disease Program, School of Medicine at the University of California San Diego.

In the first trial, the results showed that 47% of participants treated with CSF-1 achieved a 3-line or more increase in the distance-corrected near visual acuity (DCNVA) at 1-hour after drop instillation on day 15. This was in contrast to 16% reaching that level in the vehicle group. This difference reached significance (p = 0.0002).

The secondary endpoint also was reached, with 80% of participants treated with CSF-1 achieved a 2-line or greater increase in the DCNVA compared to 43% in the vehicle group; this difference also reached significance (p = 0.0001).

In addition, the distance or night vision did not decrease as a result of treatment with CSF-1.

Farid pointed out that the safety profile showed that the drug was well tolerated. The most often reported adverse events reported by over 5% of participants were pain on instillation in 5.5%, headache in 9.1%, and visual blurring in 10.9%. All episodes were considered mild, transient, and resolved without treatment.

In addition to the primary endpoint, Farid added that “meeting the secondary endpoint of a 2-line or more gain is important, especially for early presbyopes, whose vision may not yet be impaired enough to achieve gains of more than 3 lines.

The investigators were also encouraged that the distance and night vision were not affected negatively.

Post-hoc analysis

Preeya K. Gupta, MD, who is in private practice in Cary, North Carolina, reported the results of the second study, a post-hoc evaluation of the primary endpoint of sustained improvement with CSF-1 treatment.

The analysis showed that after 1 dose of CSF-1, 47% of binocularly treated participants showing an improvement of 20/40 VA level or better consistently over an 8-hour period on day 15. In addition, in participants treated both monocularly and binocularly, the percentage who achieved sustained DCNVA improvements was higher in those treated with CSF-1 compared with treatment with vehicle in those assessed for sustained 20/40 vision across all time points (p < 0.05).

“These results, which showed that a greater proportion of participants receiving CSF-1 achieved sustained functional near vision of 20/40 or better compared to vehicle when tested binocularly, demonstrates clinically meaningful improvement that would allow individuals treated with CSF-1 to more easily conduct day-to-day activities requiring near vision,” Gupta said.

Gupta added that binocular summation, which is the superiority of binocular performance over monocular performance, is involved with improved visual acuity.

“Achieving binocular summation is an important marker for evaluating efficacy of potential treatments for this age-related condition,” Gupta concluded. “In this study, the proportion of participants who reached sustained functional near vision, 20/40 or better distance-corrected near visual acuity, was higher in patients treated binocularly compared to those treated monocularly, showing the potential for CSF-1 to help patients achieve binocular summation, and ultimately improved functional near vision.”