The pharmaceutical company, Karyopharm Therapeutics has announced plans to initiate a global randomized clinical trial for low dose oral selinexor in hospitalized patients with severe COVID-19 (coronavirus).
Selinexor, marketed as XPOVIO®, is currently approved at higher doses by the Food and Drug Administration (FDA) as a treatment for patients with relapsed or refractory multiple myeloma. Selinexor is an oral, selective inhibitor of nuclear export (SINE) compound which blocks the cellular protein XPO1. In addition to its roles in cancer, XPO1 also facilitates the transport of several viral proteins from the nucleus of the host cell to the cytoplasm, and it amplifies the activities of pro-inflammatory transcription factors. SINE compounds have been shown to disrupt the replication of multiple viruses in vitro and in vivo. They have also been shown to mediate anti-inflammatory and anti-viral effects, including respiratory infections, in several animal models. In particular, SINE compounds have recently been identified as having the potential to interfere with key host protein interactions with SARS-CoV-2, the virus that causes COVID-19.
Selinexor is currently the only XPO1 inhibitor approved for commercial use by the FDA and has been extensively tested in clinical trials across numerous cancer indications worldwide since 2012. The proposed clinical trial to treat hospitalized patients with COVID-19 would be the first study of an XPO1 inhibitor in patients with severe viral infections.
Selinexor in myeloma
Selinexor received accelerated U.S. Food and Drug Administration (FDA) approval in July 2019 in combination with dexamethasone for the treatment of adult patients with relapsed refractory multiple myeloma (RRMM) who have received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors, at least two immunomodulatory agents, and an anti-CD38 monoclonal antibody. Karyopharm has also submitted a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) with a request for conditional approval of selinexor. This drug is also being evaluated in several other mid-and later-phase clinical trials across multiple cancer indications, including myeloma in a pivotal, randomized Phase 3 study in combination with bortezomib (Velcade®) and low-dose dexamethasone, for which Karyopharm announced positive top-line results in March 2020.
Find more information on myeloma, AL amyloidosis and COVID-19 here.