Losmapimod Safety and Efficacy in COVID-19

Summary

The therapeutic hypothesis for the use of losmapimod in COVID-19 disease is that increased mortality and severe disease is caused by p38 mitogen-activated protein kinase (MAPK)-mediated exaggerated acute inflammatory response resulting from SARS-CoV-2 infection. The study Sponsor hypothesizes that the early initiation of p38α/β inhibitor therapy in patients hospitalized with moderate COVID-19 who are at increased risk of a poor prognosis based on older age and elevated systemic inflammation will reduce clinical deterioration including progression to respiratory failure and death. To address this hypothesis, Fulcrum Therapeutics is conducting a Phase 3, multicenter, randomized, double-blind, placebo-controlled study that will evaluate the safety and efficacy of losmapimod versus placebo in subjects 40 and older who are hospitalized with moderate COVID-19 disease.

Timeline

Start

2020-08-28

Primary completion

2021-03-31

Completion

2021-03-31

Publications

• Background Grimes JM, Grimes KV. p38 MAPK inhibition: A promising therapeutic approach for COVID-19. J Mol Cell Cardiol. 2020 Jul;144:63-65. doi: 10.1016/j.yjmcc.2020.05.007. Epub 2020 May 16.
• Background Jimenez-Guardeno JM, Nieto-Torres JL, DeDiego ML, Regla-Nava JA, Fernandez-Delgado R, Castano-Rodriguez C, Enjuanes L. The PDZ-binding motif of severe acute respiratory syndrome coronavirus envelope protein is a determinant of viral pathogenesis. PLoS Pathog. 2014 Aug 14;10(8):e1004320. doi: 10.1371/journal.ppat.1004320. eCollection 2014 Aug.
• Background Vukmanovic-Stejic M, Chambers ES, Suarez-Farinas M, Sandhu D, Fuentes-Duculan J, Patel N, Agius E, Lacy KE, Turner CT, Larbi A, Birault V, Noursadeghi M, Mabbott NA, Rustin MHA, Krueger JG, Akbar AN. Enhancement of cutaneous immunity during aging by blocking p38 mitogen-activated protein (MAP) kinase-induced inflammation. J Allergy Clin Immunol. 2018 Sep;142(3):844-856. doi: 10.1016/j.jaci.2017.10.032. Epub 2017 Nov 17.
• Background Watz H, Barnacle H, Hartley BF, Chan R. Efficacy and safety of the p38 MAPK inhibitor losmapimod for patients with chronic obstructive pulmonary disease: a randomised, double-blind, placebo-controlled trial. Lancet Respir Med. 2014 Jan;2(1):63-72. doi: 10.1016/S2213-2600(13)70200-5. Epub 2013 Dec 5.
• Background World Health Organization (WHO). WHO R&D blueprint novel coronavirus COVID-19 therapeutic trial synopsis. Draft Feb 18, 2020.

Drugs

Indications