Planned Clinical Trial of Low Dose Selinexor in Patients with Severe COVID-19

Karyopharm Therapeutics announced plans to begin a global randomized clinical trial for low dose oral selinexor (Xpovio) in hospitalized patients with severe coronavirus disease 2019 (COVID-19). 

Currently, selinexor, a selective inhibitor of nuclear export compound which blocks the cellular protein XP01, is approved at higher doses by the FDA as a treatment for patients with relapsed or refractory multiple myeloma.

As of now, selinexor is the only XPO1 inhibitor approved by the FDA for commercial use and has been extensively tested in clinical trials across numerous cancer indications globally since 2012. The proposed clinical trial treating 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, PhD, MBA, president and chief scientific officer of Karyopharm, said in a press release. 

“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,” she added. “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 (sNDA) in the second quarter of this year.”

The role of XPO1 (also called CRM1) in SARS-CoV replication and pathogenesis was first illustrated in 2009. In a recent analysis using VIPER-based identification of Master Regulator proteins, selinexor was ranked in the top 18 of more than 400 screened drugs (top 4.5%) for interfering with virus-host interaction in SARS-CoV infected bronchial epithelial cells.

One of the notable aspects of COVID-19 is the marked pulmonary inflammation with high levels of cytokines such as IL6, IL1, IFNg, and others. Moreover, selinexor and other SINE compounds have shown 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, suggesting a particular benefit for hospitalized patients with COVID-19. 

“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,” Thomas J. Walsh, MD, professor of medicine, pediatrics, and microbiology & immunology at Weill Cornell Medicine of Cornell University, said in the release. “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.”

The company indicated that this clinical program in COVID-19 is not anticipated to impact the timing or prioritization of other key milestones, such as the planned submission of a supplemental new drug application (sNDA) for selinexor in combination with once-weekly bortezomib (Velcade) and low-dose dexamethasone as a new second line treatment for patients with relapsed or refractory multiple myeloma, which remains on schedule for the second quarter of 2020. This application will be based on results the phase III BOSTON trial.

Further, Karyopharm suggested that they have a 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. 

Reference:

Karyopharm to Evaluate Low Dose Selinexor as a Potential Treatment for Hospitalized Patients with COVID-19 [news release]. Newton, Massachusetts. Published April 7, 2020. investors.karyopharm.com/news-releases/news-release-details/karyopharm-evaluate-low-dose-selinexor-potential-treatment. Accessed April 8, 2020.