libvatrep oral (SAF312) / Bausch Health - LARVOL DELTA

Inhibition of TRPV1 by an antagonist in clinical trials is dependent on cholesterol binding. (PubMed, Cell Calcium) - "A new study by Fanet al."Structural basis of TRPV1 inhibition by SAF312 and cholesterol" sheds new light on the mechanistic structural basis of TRPV1 inhibition by SAF312 (Libvatrep), a TRPV1 antagonist, currently in phase II clinical trials. They discover that the binding site of SAF312 in TRPV1 is in close vicinity and partially overlaps with the binding site of cholesterol and that removal of cholesterol interferes with the ability of SAF312 to suppress TRPV1 current."

Journal • Pain • TRPV1

Structural basis of TRPV1 inhibition by SAF312 and cholesterol. (PubMed, Nat Commun) - "Complemented by mutagenesis experiments and molecular dynamics simulations, our research offers substantial mechanistic insights into the regulation of TRPV1 by SAF312, highlighting the interplay between the antagonist and cholesterol in modulating TRPV1 function. This work not only expands our understanding of TRPV1 inhibition by SAF312 but also lays the groundwork for further developments in the design and optimization of TRPV1-related therapies."

Journal • Pain

Ocular Pharmacology and Toxicology of TRPV1 Antagonist SAF312 (Libvatrep). (PubMed, Transl Vis Sci Technol) - "Ocular tissue and plasma pharmacokinetics (PK) were assessed following a single topical ocular dose of SAF312 (0.5%, 1.0%, 1.5%, 2.5%) in rabbits. SAF312 is a potent, selective, and noncompetitive antagonist of hTRPV1 with an acceptable preclinical safety profile for use in future clinical trials. SAF312, which was safe and well tolerated without causing delay in wound healing after PRK in rabbits, may be a potential therapeutic agent for ocular surface pain."

Journal • Pain • TRPV1

Ocular surface itch and pain: key differences and similarities between the two sensations. (PubMed, Curr Opin Allergy Clin Immunol) - "Both ocular itch and pain can be driven by nociceptive and/or neuropathic mechanisms. Identifying contributors to abnormal ocular sensations is vital for precise medical care. Novel therapeutics for these conditions aim to improve patient outcomes and quality of life."

Journal • Immunology • Neuralgia • Ocular Inflammation • Optic Neuritis • Pain

"#pharma🔴 @Novartis annonce vendredi céder la franchise en ophtalmologie Xiidra ainsi que le traitement expérimental libvatrep au spécialiste new-yorkais Bausch + Lomb . https://t.co/zjwa2XoLGM" (@Ageficom)

Topical Ocular TRPV1 Antagonist SAF312 (Libvatrep) for Postoperative Pain After Photorefractive Keratectomy. (PubMed, Transl Vis Sci Technol) - "SAF312 was well tolerated and effective in reducing ocular pain post-PRK. Topical SAF312 presents a new therapeutic option for patients undergoing PRK."

Journal • Pain • TRPV1

Topical Ocular TRPV1 Antagonist SAF312 (Libvatrep) Demonstrates Safety, Low Systemic Exposure, and No Anesthetic Effect in Healthy Participants. (PubMed, Transl Vis Sci Technol) - "This first-in-human (FIH) study evaluated the safety, tolerability, pharmacokinetics, and effect on corneal sensitivity of topical ocular SAF312 in healthy participants. SAF312 was well tolerated, with no ocular or systemic safety concerns; had no anesthetic effect, and demonstrated rapid topical absorption with low systemic exposure. This work bridges the gap between basic research and clinical care by providing FIH data of SAF312, supporting the further investigation as a potential treatment for ocular surface pain."

Journal • Anesthesia • Pain • TRPV1