On Apr. 7, 2020, Karyopharm Therapeutics announced plans to initiate a global randomized clinical trial for low dose oral selinexor in hospitalized patients with severe COVID-19. Selinexor, marketed as XPOVIO, is currently approved at higher doses by the U.S. 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 cytoplasm1, 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-19.2

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.

SINE XPO1 inhibitors have demonstrated activity against over 20 different viruses, including the RNA viruses, influenza, respiratory syncytial virus (RSV) and other common causes of respiratory infection.  XPO1 inhibition has been identified in several assays as having potential activity against SARS-CoV-2, although specific animal models have not been available to date.  One of the most important aspects of COVID-19 is the marked pulmonary inflammation with high levels of cytokines such as IL6, IL1, IFNg and others. Along these lines, selinexor and other SINE compounds have demonstrated potent anti-inflammatory activity through the inhibition of Nuclear Factor kB (NF-kB), leading to reductions in all of these cytokines in a variety of models, and this may be particularly beneficial to hospitalized patients with COVID-19.

Karyopharm’s clinical program in COVID-19 is not expected to impact the timing or prioritization of other key Company milestones, including the planned submission of a sNDA for XPOVIO (selinexor) in combination with once-weekly Velcade® (bortezomib) and low-dose dexamethasone as a new second line treatment for patients with relapsed or refractory multiple myeloma (based on the BOSTON Phase 3 trial), which remains on schedule for the second quarter of 2020. Additionally, Karyopharm has sufficient supply of selinexor for current and expected commercial supply for patients with multiple myeloma, for ongoing clinical trials in patients with various cancers, as well as for this proposed study in patients with COVID-19.