Type: p38 mitogen-activated protein kinase (MAPK) inhibitor
2021 Status: Phase III trial halted—Fulcrum said March 4 it is halting the Phase III LOSVID trial (NCT04511819) assessing losmapimod for hospitalized subjects with COVID-19, “due to significant changes in the COVID-19 treatment paradigm, including new therapeutic options and emerging vaccines.” The company said losmapimod was generally well tolerated in LOSVID, and the study’s independent data safety monitoring board did not identify any safety concerns related to losmapimod. Fulcrum plans redeploy resources to other clinical programs and discovery efforts, with a continued focus on rare diseases.
2020 Status: Fulcrum said June 10 it submitted an IND application to the FDA toward initiating a randomized, placebo-controlled, Phase III clinical trial in U.S. hospitalized patients, following Pre-IND consultation through the Coronavirus Treatment Acceleration Program (CTAP).
Fulcrum has cited earlier clinical trials that have shown losmapimod’s ability to reduce acutely inflammatory cytokines such as C-reactive protein and IL-6. The company noted that p38 MAPK is known to be an important mediator of acute response to stress, including acute inflammation. p38 inhibition has been shown to reduce angiotensin II (Ang II)-induced endothelial and organ damage in several experimental models, and may address the renin-angiotensin system imbalance that is believed to contribute to key morbidities in COVID-19 patients.
As a result, Fulcrum asserts, losmapimod could treat COVID-19 by reducing acute exaggerated pro-inflammatory responses to SARS-CoV-1 infection, and restoring the antigen-specific immune responses needed for clearance of SARS-CoV-2, potentially leading to improved clinical outcomes.
Also on June 10, Fulcrum said it closed on a $68.5 million private placement whose proceeds are intended to fund R&D expenses that include the launch of clinical development of losmapimod for COVID-19. Fulcrum signed a securities purchase agreement with a group of institutional investors and accredited investors that include EcoR1 Capital, Alyeska Investment Group, Boxer Capital, Casdin Capital, Perceptive Advisors, Samsara BioCapital, Monashee Investment Management, and Foresite Capital.
COVID-19: 300 Candidates and Counting
To navigate through the >300 potential therapeutic and vaccine options for COVID-19, GEN has grouped the candidates into four broad categories based on their developmental and (where applicable) clinical progress:
● FRONT RUNNER – the most promising therapeutics/vaccines based on clinical progress, favorable data or both.
● DEFINITELY MAYBE – earlier phases with promising partners, or more advanced candidates in development that have generated uneven data.
● KEEPING AN EYE ON… – interesting technology, attracting notable partners, or both, but preliminary data.
● TOO SOON TO TELL – longshots pending additional experimental and/or clinical data.
GEN has also tagged the most common treatment types: