Karyopharm is launching a new trial to explore the use of the oral multiple myeloma drug selinexor (XPOVIO) as a potential therapy for hospitalized COVID-19 patients.
Selinexor is an XPO1 inhibitor which has already shown benefit against respiratory viruses (including SARS-CoV) and inflammation. The study will use selinexor in low doses. It is the only XPO1 inhibitor that has been FDA approved. This would be the first time it has been used in patients with severe viral infections.
Thomas J. Walsh, MD, Professor of Medicine, Pediatrics, and Microbiology & Immunology, Weill Cornell Medicine, Cornell University said:
“Given the globally devastating impact of the COVID-19 pandemic, innovative strategies and collaborative efforts are critically needed to bring effective treatment options to patients, who are so desperately in need. 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. My staff, colleagues, and I and look forward to working with Karyopharm to better understand the role of this novel approach in improving patient outcomes of COVID19.”
Selinexor is also hoping for approval for further use in multiple myeloma when combined with Velcade and dexamethasone as part of the BOSTON study. That approval will be submitted before June 2020.
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.
The current COVID-19 virus is similar to the original SARS coronavirus that appeared in 2003. The relationship of SARS-CoV and XP01 was known as early as 2009. Selinexor helps push out certain SARS-CoV proteins out of a cell's nucleus. It also interacts with proteins that cause inflammatory respones that are associated with viral infections. Because high levels of XPO1 are found in inflammatory conditions and can cause organ damage, selinexor can also inhibit these inflammatory responses, reducing levels of inflammatory cytokines such as TNFa, IL-6 and IFNg.
In a recent analysis of potential drugs that could interfere with SARS-CoV infected bronchial cells, selinexor was ranked in the top 18 of more than 400 screened drugs. The work Karyopharm will be doing in COVID-19 will not impact their other work in myeloma or other diiseases and has a sufficient supply on hand of selinexor.
We hope that an already FDA-approved drug can provide relief to COVID-19 patients and leads to an expedited treatment for suffering patients.
about the author
Myeloma survivor, patient advocate, wife, mom of 6. Believer that patients can help accelerate a cure by weighing in and participating in clinical research. Founder of HealthTree Foundation (formerly Myeloma Crowd).