Laquinimod

Laquinimod is an orally administered small molecule with unique immunomodulatory properties that previously has been developed primarily within neurodegenerative diseases. During its years of advanced product development, clinical efficacy and safety data on laquinimod was established in more than 5000 patients, representing more than 14000 patient-years of exposure.

Laquinimod – a novel immunomodulator

Laquinimod modifies the immune response by targeting myeloid immune cells e.g. dendritic cells, monocytes/macrophages or microglia, via activation of the aryl hydrocarbon receptor (AhR). Thus, laquinimod induce differentiation of the myeloid cells towards a tologeneic phenotype, which results in induction of an anti-inflammatory immune response.

Laquinimod for treatment of eye disorders

Pre-clinical data support the use of laquinimod for treatment of the eye disorders uveitis and wet AMD. Our focus for the clinical development will be non-infectious non-anterior uveitis, an orphan disease, and a serious, sight-threatening condition. Our plan for starting clinical development in uveitis, is to use the capsule formulation already developed, and initiate a phase IIa proof-of-principle study in H2-2021. We have also, together with Leukocare AG, developed a topical ophthalmic formulation of laquinimod. Entry into clinical efficacy studies for this new formulation, requires further pre-clinical tests and a phase I trial in healthy volunteers, which we are working towards initiating also.

Unique immunomodulatory properties

Publications

Laquinimod arrests development of experimental autoimmune uveitis (EAU) and inhibits related immune processes, in the context of altered gut microbiota. Biying Xu, Xiuzhi Jia, Jihong Tang, Rachel R Caspi and Igal Gery,. J Immunol May 1, 2020, 204 (1 Supplement) 150.18. Read the abstract here.

A phase II study of laquinimod in Crohn’s disease
D’Haens G, Sandborn WJ, Colombel JF, Rutgeerts P, Brown K, Barkay H, Sakov A, Haviv A, Feagan BG. Gut. 2015 Aug;64(8):1227-35

Magnetic Resonance Spectroscopy Evaluation of Neuronal Integrity and Astrocytosis in a Phase 2 Study of Laquinimod as a Treatment for Huntington Disease (LEGATO-HD). Blair R. Leavitt, Ralf Reilmann, Mark Forrest Gordon, Karen E. Anderson, Andrew Feigin, Sarah J. Tabrizi, Julie C. Stout, Paola Piccini, Bretta Russell-Schulz, Alex L. Mackay, Beth Borowsky, Gail Rynkowski, Rita Volkinshtein, Juha-Matti Savola, Michael R. Hayden. Presented at the International congress of Parkinson’s disease and movement disorders, 2019. Read the abstract here and the poster here.

Brain MRI Volume Changes after 12 months laquinimod treatment of Huntington disease (LEGATO-HD). Ralf Reilmann, Mark Forrest Gordon, Karen E. Anderson, Andrew Feigin, Sarah J. Tabrizi5, Blair R. Leavitt, Julie C. Stout, Paola Piccini, Nicola Hobbs, Richard Manber, Beth Borowsky, Gail Rynkowski, Rita Volkinshtein, Juha-Matti Savola and Michael Hayden. Presented at the International congress of Parkinson’s disease and movement disorders, 2019. Read the abstract here and the poster here.

Quantitative Motor (Q-Motor) Assessments Suggest a Beneficial Central Effect of Laquinimod in a Phase II Study in Huntington Disease (LEGATO-HD). Ralf Reilmann, Mark Forrest Gordon, Robin Schubert, Karen E. Anderson, Andrew Feigin, Sarah J. Tabrizi, Blair R. Leavitt, Julie C. Stout, Paola Piccini, Beth Borowsky, Gail Rynkowski, Rita Volkinshtein, Juha-Matti Savola, Michael R. Hayden. Presented at the International congress of Parkinson’s disease and movement disorders, 2019. Read the abstract here and the poster here.

Legato-HD Study: A Phase 2 Study Assessing the Efficacy and Safety of Laquinimod as a Treatment for Huntington Disease. Ralf Reilmann, Mark Forrest Gordon, Karen E. Anderson, Andrew Feigin, Sarah J. Tabrizi, Blair R. Leavitt, Julie C. Stout, Paola Piccini, Beth Borowsky, Gail Rynkowski, Rita Volkinshtein, Juha-Matti Savola and Michael Hayden. Poster presentation at the annual Huntington Study Group conference, HSG 2018, in Houston, Texas November 8-10, 2018. View the complete poster here.

Legato-HD Study: A Phase 2 Study Assessing the Efficacy and Safety of Laquinimod as a Treatment for Huntington Disease. Ralf Reilmann, Mark Forrest Gordon, Karen E. Anderson, Andrew Feigin, Sarah Tabrizi, Blair R. Leavitt, Julie C. Stout, Paola Piccini, Beth Borowsky, Gail Rynkowski, Rita Volkinshtein, Juha Savola and Michael Hayden. Poster presentation at European Huntingtons Disease Network (EHDN) plenary meeting 2018. View the complete poster here.

Safety and in vivo immune assessment of escalating doses of oral laquinimod in patients with RRMS. Ziemssen T, Tumani H, Sehr T, Thomas K, Paul F, Richter N, Samara E, Spiegelstein O, Sorani E,  Bar-Ilan O, Mimrod D, Hayardeny L. J Neuroinflammation. 2017; 14: 172

Laquinimod dampens hyperactive cytokine production in Huntington’s disease patient myeloid cells
Dobson L, Träger U, Farmer R, Hayardeny L, Loupe P, Hayden MR, Tabrizi SJ. J Neurochem. 2016; 137(5): 782-94

Immune parameters of patients treated with laquinimod, a novel oral therapy for the treatment of multiple sclerosis: results from a double-blind placebo-controlled study. Stasiolek M, Linker RA, Hayardeny L, Bar Ilan O, Gold R. Immun Inflamm Dis. 2015; 3(2): 45-55

A randomized placebo-controlled phase III trial of oral laquinimod for multiple sclerosis. Vollmer T. L, Sorensen  P.S,  Selmaj K,  Zipp  F,  Havrdova  E, Cohen   J. A, Sasson  N, Gilgun-Sherki  Y,  Arnold  D. L. J Neurol. 2014; 261(4): 773-83

Placebo-controlled trial of oral laquinimod in multiple sclerosis: MRI evidence of an effect on brain tissue damage. Filippi M, Rocca MA, Pagani E, De Stefano N, Jeffery D, Kappos L, Montalban X, Boyko AN, Comi G; on behalf of the ALLEGRO Study Group. J Neurol Neurosurg Psychiatry. 2014; 85(8): 851-8

Assessment of changes in immune measures of multiple sclerosis patients treated with laquinimod. Lund BT, Kelland EE, Hayardeny L, Barilan O, Gilmore W, Weiner LP. J Neuroimmunol. 2013; 263(1-2): 108-15

Placebo-Controlled Trial of Oral Laquinimod for Multiple Sclerosis. Comi G, Jeffery D, Kappos L, Montalban X,  Boyko A, Rocca MA, M.D., Filippi M, for the ALLEGRO Study Group. N Engl J Med. 2012; 366: 1000-9

Effect of Laquinimod on MRI-monitored disease activity in patients with RRMS: a multicenter, randomized, double-blind, placebo-controlled phase IIb study. Comi G, Pulizzi A, Rovaris M, Abramsky O, Arbizu T, Boiko A, Gold R, Havrdova E, Komoly S, Selmaj KW, Sharrack B, Filippi M. The Lancet 2008; 371(9630): 2085-92

Treatment with laquinimod reduces development of active MRI lesions in relapsing multiple sclerosis. Polman C, Barkhof F, Sandberg-Wollheim M, Linde A, Nordle O & Nederman T. Neurology. 2005; 64(6): 987-91