Safety and Efficacy of LP-10 Liposomal Tacrolimus in Oral Lichen Planus: A Multicenter Phase 2 Trial

Michael T Brennan 1, Jennifer Frustino 2, Kamal Al-Eryani 3, Herve Sroussi 4, Jennifer L Parish 5, Hirak B Routh 5, Sunil Dhawan 6, Gerald L Klein 7, Michael B Chancellor 8, Alessandro Villa 9

Affiliations

1 Department of Oral Medicine/Oral and Maxillofacial Surgery, Wake Forest University School of Medicine, Atrium Health Carolinas Medical Center, Charlotte, NC, USA.

2 Erie County Medical Center, Buffalo, NY, USA.

3 University of California San Francisco, San Francisco, CA, USA.

4 Brigham and Women's Hospital, Boston, MA, USA.

5 Paddington Testing Co, Inc, Philadelphia, PA, USA.

6 Center for Dermatology Clinical Research, Inc, Fremont, CA, USA.

7 MedSurgPI LLC, Brody School of Medicine, ECU, Franklinton, NC, USA.

8 Lipella Pharmaceuticals, Inc., Suite 505, 7800 Susquehanna, Pittsburgh, PA, 15208, USA. Michael.chancellor@lipella.com.

9 Oral Medicine and Oral Oncology Miami Cancer Institute, Baptist Health South Florida, Miami, FL, USA.

PMID: 41174333. DOI: 10.1007/s13555-025-01572-2

Abstract

Introduction: Oral lichen planus (OLP) is a serious chronic inflammatory condition with malignant transformation potential affecting six million Americans which has no US Food and Drug Administration (FDA)-approved therapy. LP-10, a novel liposomal tacrolimus oral rinse, overcomes the poor adherence to oral surfaces and inconsistent drug delivery limitations of existing treatments.

Methods: This phase 2a multicenter dose-ranging study evaluated LP-10 safety and efficacy in symptomatic OLP. Twenty-seven adults (22 female, 5 male) received a 10-mL oral rinse of LP-10 at 0.25 mg, 0.5 mg, or 1.0 mg of tacrolimus, for 3 min twice daily for 4 weeks. Safety assessments included monitoring of adverse events, laboratory studies, and tacrolimus blood levels. Efficacy was measured by investigator global assessment (IGA), reticulation/erythema/ulceration (REU) score, pain/sensitivity numerical rating scale (NRS), OLP symptom severity measure (OLPSSM), and patient global response assessment (GRA).

Results: All participants completed treatment without discontinuation or serious adverse events. Treatment-related treatment-emergent adverse events were mild/moderate (50 mild, 4 moderate). LP-10 demonstrated exceptional pharmacokinetic safety with mean tacrolimus levels remaining < 1.0 ng/mL in 75% of post-baseline measurements; the maximum individual level (4.5 ng/mL) remained well below the toxicity threshold (15 ng/mL) suggesting little absorbance into the blood. All efficacy endpoints showed statistically significant and clinically meaningful improvements at week 4: mean and standard deviation (SD) values for IGA decreased from 3.5 ± 0.51 to 1.8 ± 1.37 (p < 0.0001), pain NRS from 6.8 ± 1.90 to 2.3 ± 2.53 (p < 0.0001), sensitivity NRS from 7.2 ± 1.71 to 2.9 ± 2.29, REU from 26.5 ± 10.4 to 13.2 ± 8.15 (p < 0.0001). Of the 23 participants who responded to the GRA, approximately 78% participants reported that their quality of life was "moderately better" or "very much better" as compared to when they started the study, across all doses. All prior corticosteroid failures (5/5) responded, with benefits sustained through 2-week follow-up.

Conclusions: LP-10 demonstrated excellent safety with minimal systemic absorption and clinically meaningful efficacy, representing substantial improvement over existing therapies for this serious condition with significant unmet medical need. Larger controlled studies are warranted to confirm these promising findings.

Clinical trial registration: NCT06233591.

Keywords: Dose-ranging study; Liposome; Oral lichen planus; Oral mucosa; Phase 2 clinical trial; Tacrolimus.