Key Takeaways

  • Bausch + Lomb plans to advance its lifitegrast/PFHO dry eye combination into phase 3 using a Day 15 primary endpoint after the phase 2 study  produced a significant prespecified Day 15 result
  • BL1332 significantly reduced pain intensity in a phase 1b capsaicin challenge study, providing clinical evidence supporting TRPV1 blockade as a potential approach to ocular surface pain

Bausch + Lomb is advancing two investigational ophthalmic therapies following new clinical results, with a dual-action dry eye treatment headed for phase 3 development and the TRPV1 antagonist BL1332 continuing development for ocular surface pain.

The company reported results from a phase 2 study of its combination of 5% lifitegrast and perfluorohexyloctane (PFHO), as well as a phase 1b study evaluating BL1332 0.30% ophthalmic solution in a capsaicin-induced ocular pain model.

“Helping people see better to live better starts with tackling the challenges patients still face every day,” Brent Saunders, CEO of Bausch + Lomb, said in a news release. “These results support our approach to developing differentiated therapies that have the potential to address significant unmet needs and change the standard of care in eye health.”

Dual-action dry eye candidate moves toward Phase 3

Bausch + Lomb’s investigational dry eye drop combines lifitegrast, the active ingredient in Xiidra, with PFHO, the active ingredient in Miebo. The twice-daily therapy is intended to simultaneously address ocular surface inflammation and tear evaporation.

A 4-week, randomized, double-masked, parallel-group, active-controlled phase 2 trial enrolled 443 adults with dry eye disease across 6 treatment arms. These included the combination therapy, lifitegrast alone, PFHO alone, and 3 vehicle masking controls.

The study did not meet its primary endpoint of superiority to lifitegrast alone for change from baseline in total corneal fluorescein staining (tCFS) at Day 29. Although the numerical result favored the combination, the difference was not statistically significant (P=.196).

A prespecified secondary analysis at Day 15, however, demonstrated a statistically significant reduction in mean tCFS change from baseline with the combination compared with lifitegrast alone (P=.0007). Bausch + Lomb noted that Day 15 has been accepted by the FDA as a registrational primary endpoint timepoint for tCFS.

At Day 15, 41.6% of patients receiving the combination achieved an improvement of at least 3 units in tCFS, compared with 18.8% receiving lifitegrast alone and 31.6% receiving PFHO alone.

No new safety signals were identified, according to the company, and the safety findings across the treatment groups were consistent with the established profiles of Xiidra and Miebo.

Bausch + Lomb said it plans to use Day 15 as the primary endpoint timepoint when the program advances into phase 3. The company also noted that the investigational drop delivered the phase 2 findings using more than 50% less lifitegrast volume than Xiidra and at half the dosing frequency of Miebo.

“This was the first time this combination has been studied in humans, and it did exactly what a phase 2 should do: demonstrated a rapid, robust treatment effect and told us precisely when to measure it,” said Yehia Hashad, MD, executive vice president of R&D and chief medical officer at Bausch + Lomb.

Details of the Phase 3 program are expected to be announced in the coming months.

BL1332 targets ocular pain signaling

The company also reported positive phase 1b findings for BL1332, a topical TRPV1 antagonist being developed to target pathways involved in ocular pain signaling.

The study evaluated BL1332 0.30% ophthalmic solution in healthy adults using a capsaicin-induced ocular pain challenge. According to Bausch + Lomb, the trial met its primary endpoint, with BL1332 producing a statistically significant reduction in pain intensity compared with vehicle.

Five seconds after the capsaicin challenge, BL1332-treated eyes had a 5.5-point reduction in mean pain intensity compared with vehicle (P<.0001).

Exploratory analyses showed complete pain resolution in 68.2% of BL1332-treated eyes compared with none of the vehicle-treated eyes (P<.0001). No BL1332-treated eyes reported severe pain, compared with 36.4% of vehicle-treated eyes (P<.01).

Mean pain duration following the capsaicin challenge was 1.6 seconds with BL1332 versus 37.8 seconds with vehicle (P<.0001). The company reported no new safety signals.

“These results provide the first clinical evidence that targeting TRPV1 can meaningfully reduce ocular pain in humans that have not just undergone surgery,” Dr. Hashad said. “They also strengthen our confidence in the mechanism as we continue evaluating BL1332 in patients with clinically relevant pain conditions.”

BL1332 is now being evaluated in an ongoing phase 2 study involving patients with pain following photorefractive keratectomy surgery. Topline results are expected within the next few months.

Bausch + Lomb said the mechanism could ultimately have applications beyond postsurgical pain, including ocular surface pain associated with dry eye disease and other acute and chronic ocular disorders. Future development plans will depend on additional clinical findings and regulatory discussions.