Bausch + Lomb (NYSE:BLCO) said it plans to advance a dual-action dry eye treatment into Phase III development after a Phase II study showed statistically significant improvement in corneal staining at day 15, although the trial did not meet its primary endpoint at day 29.
The company also reported Phase Ib results for BL1332, an ocular surface pain candidate designed to block the TRPV1 receptor. The study met its primary endpoint in a capsaicin-induced pain model in healthy volunteers, according to the company.
Dry Eye Candidate Shows Earlier Effect
Bausch + Lomb’s dual-action eye drop combines the active ingredients in MIEBO and XIIDRA. MIEBO’s active ingredient, perfluorohexyloctane, or PFHO, is intended to reduce tear evaporation, while XIIDRA’s active ingredient, lifitegrast, acts as an anti-inflammatory.
Mayssa Attar, head of pharmaceutical R&D, said the four-week randomized, double-masked, active-controlled study enrolled 443 patients across six treatment and vehicle-control arms. The prespecified primary endpoint was change from baseline in total corneal fluorescein staining at day 29 compared with lifitegrast alone.
The combination treatment was numerically better than lifitegrast at day 29 but did not achieve statistical significance. However, at the prespecified day 15 assessment, the dual-action drop significantly reduced corneal staining versus lifitegrast alone, with a p-value of 0.0007.
At day 15, 41.6% of patients receiving the dual-action drop achieved a three-unit improvement in corneal staining, compared with 18.8% for lifitegrast alone and 31.6% for PFHO alone. The company said the combination treatment was administered twice daily, compared with four daily doses for PFHO alone, and used a 12-microliter drop volume versus 35 microliters in the lifitegrast-alone arm.
Attar said the combination numerically outperformed lifitegrast across several symptom-resolution measures, including itching, light sensitivity, blurred vision, irritation, burning and foreign-body sensation. Results versus PFHO were mixed, with the combination performing better on some measures and comparably or slightly below PFHO on others.
No new safety signals were observed, the company said. Instillation-site irritation occurred in 11.9% of patients receiving the combination therapy, compared with 21.2% for lifitegrast alone, while dysgeusia occurred in 10.9% and 15.2% of patients, respectively.
Yehia Hashad, Bausch + Lomb’s head of R&D, said the company expects to use day 15 as the primary endpoint in its next trial, while continuing to assess later time points. Management said it plans to use modeling and simulation work to determine the Phase III dose and dosing frequency.
During the question-and-answer session, Hashad said total corneal fluorescein staining has been used as an approvable endpoint in other programs. He added that the company has not yet said it has received FDA agreement on a 15-day corneal-staining endpoint, stating that it expects to speak with the agency.
BL1332 Pain Study Meets Primary Endpoint
BL1332 is a topical TRPV1 antagonist intended to interrupt pain signaling on the ocular surface. According to the company, the molecule is approximately 100 times more potent and more water-soluble than its earlier-generation TRPV1 candidate, BL-1312.
The Phase Ib trial consisted of two parts. In the first, six healthy participants were used to identify a capsaicin concentration that produced a target pain response. In the second, 22 participants entered a double-masked, two-period crossover study in which each participant received BL1332 and a vehicle placebo on separate occasions.
The primary endpoint measured pain intensity five seconds after a capsaicin challenge. Mean pain intensity was 0.6 for BL1332 and 6.1 for vehicle, a statistically significant difference, the company said.
- 68.2% of participants receiving BL1332 reported complete pain resolution, compared with none receiving vehicle.
- Mean pain duration was 1.6 seconds for BL1332 versus 37.8 seconds for vehicle.
- No participants on BL1332 reported severe pain, defined as a score of 7 or higher, while more than one-third of vehicle-treated participants did.
Attar said no treatment-emergent adverse events, serious adverse events or discontinuations were reported in either eye during the study. She also said an earlier Phase I study designed to assess systemic exposure and thermoregulatory safety found no hyperthermia, an issue that had affected earlier systemic TRPV1 antagonist programs.
Bausch + Lomb expects Phase II results for BL1332 in post-surgical ocular pain later in the year. Management said the Phase Ib findings support evaluating the candidate in additional acute and chronic ocular pain conditions, including pain associated with dry eye disease.
About Bausch + Lomb (NYSE:BLCO)
Bausch + Lomb Corporation operates as an eye health company in the United States, Puerto Rico, China, France, Japan, Germany, the United Kingdom, Canada, Russia, Spain, Italy, Mexico, Poland, South Korea, and internationally. It operates in three segments: Vision Care, Pharmaceuticals, and Surgical. The Vision Care segment provides contact lens that covers the spectrum of wearing modalities, including daily disposable and frequently replaced contact lenses; and contact lens care products comprising over-the-counter eye drops, eye vitamins, and mineral supplements that address various conditions, such as eye allergies, conjunctivitis, dry eye, and redness relief.
