Bausch + Lomb Missed Its Dry Eye Endpoint. The Result Still Points to Phase 3

A Phase 2 result at Day 15 is sending the dual-action drop into Phase 3, in a field where when you measure can matter as much as what you measure.

Bausch + Lomb (Nasdaq: BLCO) has spent years building a significant position in dry eye disease. It markets Xiidra, which targets inflammation, and Miebo, which is designed to reduce tear evaporation. Now it wants to combine the active ingredients of both into a single eye drop. No approved therapy addresses both the inflammatory and evaporative drivers of the disease at once, which is the gap the company is aiming at.

A 443-patient Phase 2 study of the dual-action drop did not meet its primary endpoint at Day 29, where results numerically favored the combination over Xiidra alone in total corneal fluorescein staining without reaching statistical significance. Bausch + Lomb is moving toward Phase 3 anyway. The reason can be found two weeks earlier.

A prespecified secondary analysis at Day 15 showed a statistically significant improvement in corneal staining for the combination over Xiidra alone. About 41.6% of patients receiving the combination achieved at least a three-unit improvement in staining, compared with 18.8% receiving lifitegrast alone and 31.6% receiving perfluorohexyloctane alone. This was the first time the combination had been studied in humans, and the company had selected Day 29 without prior data showing when a combined effect would emerge. The drop also produced that result using more than 50% less lifitegrast than Xiidra and half the dosing frequency of Miebo.

The FDA accepts Day 15 as a registrational primary endpoint timepoint for corneal staining, which gives the company a path into Phase 3. Chief Medical Officer Yehia Hashad said the study “told us precisely when to measure it.” Bausch + Lomb is also weighing adjustments to dosing or formulation as it works toward the harder objective: demonstrating superiority not only to Xiidra, but to Miebo as well.

A Phase 2 is meant to teach a company how to design a Phase 3. This one did, even as the primary endpoint came up short. It also illustrates what makes dry eye such a demanding target.

Why Dry Eye Is Hard to Measure

Dry eye sounds deceptively simple. In reality, it is a multifactorial disease that can involve inflammation, excessive tear evaporation, insufficient tear production, damage to the ocular surface and, in some patients, a pain component that does not necessarily track with visible signs.

That creates a recurring design question for drug developers. A treatment can have real biological activity and still not separate cleanly from control, depending on the endpoint, the patient population or the timepoint selected. Bausch + Lomb had the advantage of working with two mechanisms that are already commercially validated, and the first human study of the combination still turned on when the measurement was taken. For developers pursuing entirely new mechanisms, the calibration problem is larger.

Aldeyra Therapeutics (Nasdaq: ALDX) has been working through a version of it for years. Reproxalap has drawn three Complete Response Letters, most recently in March, none citing safety or manufacturing. What the FDA has questioned is whether the accumulated clinical package establishes effectiveness with enough consistency across studies.

Aldeyra reads its own record differently, pointing to multiple trials and endpoints that favored reproxalap, including a Phase 3 dry eye chamber trial that met its primary endpoint on ocular discomfort in 2025. The company continues to press the case, and following a Type A meeting with the FDA in June has been working toward another regulatory discussion on a potential resubmission.

The distinction matters. This is not a program that produced one failed study. It is a disagreement about whether a large and varied dataset adds up to substantial evidence, which is a particularly dry-eye kind of question.

Different Mechanisms, Same High Bar

Other developers are approaching the disease from very different biological directions. Palatin Technologies (Nasdaq: PTN) developed PL9643, an agonist of the melanocortin-1 receptor, through the first of three planned Phase 3 MELODY studies and reported positive results from MELODY-1. Its pipeline lists MELODY-2 and MELODY-3 as potential 2026 starts. In January, Palatin sublicensed the program to Altanispac Labs in a transaction that included approximately $3.8 million of non-cash debt cancellation, keeping rights to future payments and royalties while concentrating its own resources elsewhere.

Private biotech Stuart Therapeutics is trying something different again. Its ST-100 program is based on PolyCol, a platform of synthetic collagen-mimetic peptides designed to repair damaged extracellular matrix structures in ocular tissue. A Phase 2 study showed statistically significant improvements in measures including corneal staining and tear production, although symptom improvement did not separate from vehicle.

The subsequent Phase 3a study produced a split result of the kind this field keeps generating. ST-100 did not reach statistical significance on its Schirmer responder primary endpoint, while delivering statistically significant improvements in fluorescein staining. Stuart is now planning two Phase 3b studies and a year-long safety trial, with recruitment expected to begin in late Q3 2026.

Taken together, these programs are not variations on the same scientific idea. Bausch + Lomb is combining anti-inflammatory and anti-evaporative mechanisms. Aldeyra is targeting reactive aldehyde species. Palatin is working through melanocortin signaling. Stuart is pursuing tissue repair. Four independent bets on a disease that has resisted a single explanation, each now working out which measure captures what its drug actually does.

When Dry Eye Turns Out to Be Something Else

OKYO Pharma (Nasdaq: OKYO) offers perhaps the clearest example of how blurred those boundaries can become. Urcosimod, previously known as OK-101, was initially evaluated in a 240-patient Phase 2 dry-eye study. The trial assessed conventional dry-eye signs and symptoms, but another signal caught the company’s attention: the 0.05% dose produced statistically significant improvement versus placebo in ocular pain at several measured timepoints.

OKYO followed that signal away from conventional dry eye and into neuropathic corneal pain, or NCP. The distinction is significant. NCP results from dysfunction of corneal nerves and can produce burning, severe dryness, foreign-body sensation and pain. Those symptoms overlap with dry eye, and OKYO’s materials note that NCP is commonly misdiagnosed as dry eye disease.

A small Phase 2a proof-of-concept study in NCP produced encouraging pain reductions and gave OKYO enough to design a larger program, though the dataset is limited, with 18 patients randomized before the study was terminated early for operational reasons. The planned Phase 3 NEPTUNE study is expected to enroll approximately 111 adults, with reduction in ocular pain at Week 12 as the primary endpoint.

A dry-eye study steered the company toward what it believes is a more precisely defined disease and a more appropriate endpoint. That may be one of the more instructive stories in the field.

What Bausch Learned at Day 15

Bausch + Lomb does not need its dual-action drop to drive its immediate growth. Management has positioned the program as a later-decade opportunity and estimates potential peak sales of roughly $700 million if development and commercialization are successful. What makes the Phase 2 result interesting now is the difference between Day 15 and Day 29.

The company’s read is that the combination works faster than Xiidra alone. Phase 3 will prospectively test that hypothesis at the earlier timepoint, while Bausch + Lomb continues working through dosing and formulation as it seeks to show superiority against both components. Saunders has said the company believes it can demonstrate that, and it still has to prove it in a pivotal study.

The episode captures something that extends well beyond one drug. In dry eye, finding an active molecule is only part of the job. Developers also have to determine which patients are most likely to benefit, which component of a heterogeneous disease they are actually treating, which endpoint best captures that benefit and when to measure it. For Bausch + Lomb, the difference between a Phase 2 miss and a path to Phase 3 may have been 14 days. For the smaller companies pursuing the same market, getting those decisions right is the work.