ATX01 is currently in Phase 2 clinical development in CIPN and EM. ATX01 combines the active ingredient amitriptyline with a bespoke proprietar topical formulation. Oral amitriptyline (AMT) has long been used as a tricyclic antidepressant, inhibiting the reuptake of monoamines such as norepinephrine and serotonin.

AMT is known to exert some central analgesic effect; The respective importance of its Sodium-channel inhibiting properties and mood-altering activities is unknown. However oral AMT has limited efficacy on peripheral neuropathic pain such as CIPN and induces rate limiting side effects.

By contrast, when AMT is applied topically, it reaches the peripheral sensory neurons in the skin and effectively acts as an inhibitor of nociceptive voltage-gated sodium channels Nav1.7, Nav1.8 and Nav1.9 blocking the generation and transduction of the pain message. Genevois et al established and published the work establishing this activity of amitriptyline in 20195.

ATX01’s hydrogel formulation enables relevant concentrations of amitriptyline to access the target nerve fibres in the feet and hands in the most direct manner, whilst minimizing passage in the bloodstream6 and the risk of systemic side-effects and drug interactions.

OBSERVATIONAL STUDIES

AlgoTx was initially inspired to develop ATX01 by the exploratory work of a few physicians, which was ultimately published in two prospective studies of 44 (20197) and 25 (20215) patients at major French hospitals. They show the patient’s self-reported pain rating on a scale from 1 (no pain) to 10 (maximum pain), typically reduced by three to five points, moving from unbearable to bearable pain, and consequently enabling patients to restart chemotherapy.

Whilst exploratory, those publications shed an encouraging light on ATX01’s potential medical benefit for patients.

Squiggle Graphic
PUBLICATIONS
Ref 1Cavaletti G, Marmiroli P.

Chemotherapy-induced peripheral neurotoxicity.
Nat Rev Neurol 2010;6:657–66
https://pubmed.ncbi.nlm.nih.gov/21060341/

Ref 2Hershman DL, Lacchetti C, Dworkin RH, Smith EML, Bleeker J, Cavaletti G, Chauhan C, Gavin P, Lavino A, Lustberg MB, Paice J, Schneider B, Smith ML, Smith T, Terstriep S, Wagner-Johnston N, Bak K, Loprinzi CL.

Prevention and management of chemotherapy-induced peripheral neuropathy in survivors of adult cancers: American Society of Clinical Oncology Clinical Practice Guideline.
J Clin Oncol 2014;32:1941–67
https://pubmed.ncbi.nlm.nih.gov/24733808/

Ref 3Chenkun Wang, Si Chen, Weiwei Jiang

Treatment for chemotherapy-induced peripheral neuropathy: A systematic review of randomized control trials Front.
Pharmacol., 23 December 2022_Sec. Drugs Outcomes Research and Policies_Volume 13 - 2022
https://www.frontiersin.org/articles/10.3389/fphar.2022.1080888/full

Ref 4Lesley A Colvin.

Chemotherapy-induced peripheral neuropathy: where are we now?
Pain. 2019 May;160 Suppl 1(Suppl 1):S1-S10.
https://pubmed.ncbi.nlm.nih.gov/31008843/

Ref 5Genevois et al.,

Analgesic Effects of Topical Amitriptyline in Patients With Chemotherapy-Induced Peripheral Neuropathy: Mechanistic Insights From Studies in Mice
J Pain 22: 440-453, 2021:
https://pubmed.ncbi.nlm.nih.gov/33227509/

Ref 6F. Catus, J. Ellrich, C. Greco, F. Lokiec, P. Picaut

Topical Amitriptyline Hydrochloride in Chemotherapy-Induced Peripheral Neuropathy (CIPN) – Pharmacokinetic and Safety Data
Poster presented at AMSCC 2022

Ref 7Julien Rossignol, Benoit Cozzi, François Liebaert, Séverine Hatton, Marcel-Louis Viallard, Olivier Hermine, Céline Greco.,

High concentration of topical amitriptyline for treating chemotherapy-induced neuropathies
Supp Care in Cancer, 2019
https://pubmed.ncbi.nlm.nih.gov/30607681/

Squiggle Graphic
INTELLECTUAL PROPERTY

ATX01 is protected by a comprehensive suite of patents filed globally and already granted in numerous geographies.