A global randomized clinical trial for low dose oral Xpovio (selinexor) in hospitalized patients with severe COVID-19 aims to evaluate the drug as a potential treatment option.
Karyopharm Therapeutics Inc. sponsors the drug.
FDA has approved Xpovio as a treatment for patients with relapsed or refractory multiple myeloma. Selinexor is an oral, selective inhibitor of nuclear export compound that 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-19.2
Selinexor is 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.
“While Karyopharm’s clinical development strategy until now has been focused on patients with various types of cancer, there is increasing evidence that XPO1 inhibition could play an important role in the treatment of patients with viral infections including SARS-CoV-2,” Sharon Shacham, president and chief scientific officer of Karyopharm, said in a statement.
“As the medical community is urgently seeking innovative ways to address the COVID-19 pandemic, based on recent scientific data, we have decided to evaluate the potential for selinexor in the treatment of patients with COVID-19. We look forward to working with clinical investigators and regulators across the globe as expeditiously as possible to determine the next steps for this new initiative.
“Additionally, we continue to move our oncology programs forward including the expected submission of our BOSTON supplemental New Drug Application in the second quarter of this year,” Shacham said.
“I am highly encouraged by the scientific rationale of studying selinexor, which targets both virus and immune-mediated injury, for treatment of patients with severe COVID-19,” Thomas J. Walsh, professor of medicine, pediatrics, and microbiology & immunology, Weill Cornell Medicine, Cornell University, said in a statement.
SINE XPO1 inhibitors have demonstrated activity against over 20 different viruses, including the RNA viruses, influenza, respiratory syncytial virus 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.
