Bausch + Lomb advances dual-action dry eye drop to phase 3, reports positive BL1332 pain data

Bausch + Lomb has announced plans to advance 2 investigational first-in-class ophthalmic therapies into expanded clinical development, citing recent trial results in dry eye disease and ocular surface pain. According to a company press release, a dual-action eye drop combining lifitegrast 5% and perfluorohexyloctane (PFHO) will move into phase 3 development, while a topical TRPV1 antagonist, BL1332, demonstrated statistically significant pain reduction in a phase 1b challenge model.¹

Yehia Hashad, MD, executive vice president, R&D and chief medical officer of Bausch + Lomb, said in the release that the phase 2 study delivered exactly what he expected from that stage of development: a clear treatment effect paired with a defined timepoint for measuring it, marking the first time this drug combination had been studied in humans.¹

"Ocular surface pain is challenging because what a patient feels does not always correlate directly with the signs we can see on examination. Many of the therapies available today are designed to address an underlying condition, such as inflammation, with the expectation that pain will improve as that condition improves. But we currently do not have an approved therapy specifically designed to interrupt the neurosensory pathway responsible for ocular surface pain itself," Hashad told Ophthalmology Times.

Dual-action dry eye drop: phase 2 design and key findings

The phase 2 study was a 4-week, randomized, double-masked, parallel-group, active-controlled trial enrolling 443 patients aged 18 years or older across 6 arms: the dual-action combination, lifitegrast alone, PFHO alone, and 3 vehicle masking controls, according to the press release. The study did not meet its primary endpoint: superiority over lifitegrast alone in reducing total corneal fluorescein staining (tCFS) from baseline at Day 29 (p=0.196), though results numerically favored the combination.¹

A pre-specified secondary analysis at Day 15, a timepoint the company states has been accepted by the FDA as a registrational primary endpoint for tCFS, did reach statistical significance: the dual-action drop showed a greater mean reduction from baseline tCFS compared with lifitegrast alone (p=0.0007). At that timepoint, 41.6% of patients in the combination arm achieved a ≥3-unit improvement in tCFS, versus 18.8% in the lifitegrast arm and 31.6% in the PFHO arm. The safety profile was described as consistent with the established profiles of the individual components, with no new signals identified. Bausch + Lomb reported that the combination achieved these results with more than 50% less lifitegrast volume than XIIDRA and at half the dosing frequency of MIEBO.¹

Phase 3 development will use Day 15 as the primary endpoint timepoint. The company stated it intends to design those studies to demonstrate superiority over both individual therapies, with program details to follow in the coming months.¹

BL1332: phase 1b design and primary results

The phase 1b study evaluated BL1332 0.30% ophthalmic solution using a capsaicin-induced ocular pain challenge model in healthy adult participants, according to the press release. The study met its primary endpoint, demonstrating a statistically significant reduction in pain intensity versus vehicle (p<0.0001). At 5 seconds following capsaicin challenge, BL1332-treated eyes experienced a 5.5-point reduction in mean pain intensity. In exploratory analyses, 68.2% of BL1332-treated eyes achieved complete pain resolution versus 0% of vehicle-treated eyes (p<0.0001), and no BL1332-treated eyes reported severe pain compared with 36.4% of vehicle-treated eyes (p<0.01). Mean pain duration was also notably shorter: 1.6 seconds versus 37.8 seconds (p<0.0001). The safety profile was described as acceptable, with no new signals.¹

The company is currently evaluating BL1332 in an ongoing phase 2 study in patients experiencing pain following photorefractive keratectomy (PRK), with topline results expected within the coming months.¹

Clinical context and unmet needs

Dry eye disease is a multifactorial condition with inflammatory and evaporative components; approved therapies to date have generally addressed one mechanism at a time.² Lifitegrast, a lymphocyte function-associated antigen-1 antagonist, targets ocular surface inflammation,³ while PFHO reduces tear evaporation via a distinct physical mechanism. No currently approved single agent addresses both pathways simultaneously, representing a recognized gap in care.

Ocular surface pain similarly lacks an approved therapy targeting neurosensory mechanisms directly. "TRPV1 is one of the primary sensors of pain on the ocular surface. The premise behind BL1332 is that by antagonizing that receptor, we may be able to interrupt the signaling cascade that produces pain rather than addressing it indirectly," Hashad told Ophthalmology Times.

Limitations and considerations

The dual-action drop's failure to meet its Day 29 primary endpoint warrants caution, even given the strength of the Day 15 secondary finding. The Day 15 result, while pre-specified, emerged from a study powered and designed around a later timepoint, and the phase 3 program will be critical to establishing the combination's superiority claim. For BL1332, the phase 1b capsaicin challenge model, while mechanistically informative, involves healthy volunteers and a pharmacologically induced pain stimulus rather than patients with clinically relevant ocular pain disorders; generalizability to post-PRK or chronic pain populations remains to be demonstrated in the ongoing phase 2 study. No ClinicalTrials.gov registration numbers were provided for either study in the press release.

References
1. Bausch + Lomb Corporation. Bausch + Lomb advancing two first-in-class eye health therapies based on trial results. News release. August 24, 2026. Accessed August 24, 2026. https://www.bausch.com/newsroom/news/?id=361
2. Stapleton F, Alves M, Bunya VY, et al. TFOS DEWS II epidemiology report. Ocul Surf. 2017;15(3):334-365. https://doi.org/10.1016/j.jtos.2017.05.003
3. Donnenfeld ED, Karpecki PM, Majmudar PA, et al. Safety of lifitegrast ophthalmic solution 5.0% in patients with dry eye disease: a 1-year, multicenter, randomized, placebo-controlled study. Cornea. 2016;35(6):741-748. https://doi.org/10.1097/ICO.0000000000000803