Laquinimod

Laquinimod, är en substans i tablettform med unika immunmodulerande egenskaper som tidigare har utvecklats främst inom neurodegenerativa sjukdomar. Under åren av sen klinisk utveckling genererades kliniska data avseende klinisk effekt och säkerhet för laquinimod i fler än 5 000 patienter, vilket motsvarar mer än 14 000 patientår av exponering för laquinimod.

Laquinimod – en ny immunmodulator

Laquinimod modifierar immunsvaret genom att påverka myeloida immunceller t. ex. dendritiska celler, monocyter/macrofager or mikroglia, genom att aktivera aryl hydrocarbon receptorn (AhR). På detta vis inducerar laquinimod differentiering av the myeloida cellerna på ett sätt som gör dem tolerogena, vilket resulterar i en induktion av ett anti-inflammatoriskt immunsvar.

Laquinimod för behandling av ögonsjukdomar

Prekliniska data stöder användningen av laquinimod för behandling av de två ögonsjukdomarna uveit och våt AMD. Vårt fokus de kommande 12 månaderna kommer att vara på att öka förståelsen för den terapeutiska potentialen hos laquinimod genom ytterligare prekliniska studier och att definiera hur man bäst kan utveckla laquinimod som topikal behandling för dessa sjukdomar.

Unika immunmodulerande egenskaper

Publikationer

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. Läs abstraktet här.

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. Presenterat på den internationella kongressen ”Parkinson’s disease and movement disorders”, 2019. Läs abstraktet här och hela postern här.

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. Presenterat på den internationella kongressen ”Parkinson’s disease and movement disorders”, 2019. Läs abstraktet här och hela postern här.

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. Presenterat på den internationella kongressen ”Parkinson’s disease and movement disorders”, 2019. Läs abstraktet här och hela postern här.

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 vid den årliga konferensen i Huntington Study Group, HSG 2018, Houston, Texas 8-10 november 2018. Läs hela postern här.

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. Läs hela postern här.

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,  BarIlan O, Mimrod D, Hayardeny L. J Neuroinflammation. 2017; 14: 172

Laquinimod treatment in the R6/2 mouse model
Ellrichmann G, Blusch A, Fatoba O, Brunner J, Hayardeny L, Hayden M, Sehr D, Winklhofer KF, Saft C, Gold R. Sci Rep. 2017; 7: 4947

Laquinimod rescues striatal, cortical and white matter pathology and results in modest behavioural improvements in the YAC128 model of Huntington disease
Garcia-Miralles M, Hong X, Tan LJ, Caron NS, Huang Y, To XV, Lin RY, Franciosi S, Papapetropoulos S, Hayardeny L, Hayden MR, Chuang KH, Pouladi MA. Sci Rep. 2016; 6:31652

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