A Global Randomized Trial Planned for Selinexor to Treat COVID-19

Apr 08, 2020

Low-dose selinexor will be evaluated in a global randomized clinical trial for hospitalized patients with severe coronavirus disease 2019. This oral selective inhibitor has previously been approved at higher doses by the FDA for the treatment of patients with relapsed/refractory multiple myeloma. The plans to initiate this clinical trial were announced in a press release from Karyopharm Therapeutics Inc, developer of the drug.

Low-dose selinexor (Xpovio) will be evaluated in a global randomized clinical trial for hospitalized patients with severe coronavirus disease 2019 (COVID-19). This oral selective inhibitor has previously beenapproved at higher doses by the FDA for the treatment of patients with relapsed/refractory multiple myeloma. The plans to initiate this clinical trial were announced in a press release from Karyopharm Therapeutics Inc, developer of the drug.

“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, Weill Cornell Medicine, Cornell University, said in a press 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 ofCOVID19.”

This clinical trial of selinexor in patients with COVID-19 will be the first to treat patients with severe viral infections with an XPO1 inhibitor. Selinexor is currently the only FDA-approved XPO1 inhibitor for commercial use. The agent has been tested extensively in clinical trials across many cancer types around the world since 2012.

The agent is a selective inhibitor of nuclear export (SINE) compound that blocks cellular protein XPO1. The protein facilitates the transportation of several vital proteins from the nucleus of the host cell to the cytoplasm, amplifying the activities of pro-inflammatory transcription factors.

Specifically, SINE compounds have the potential to interfere with key host protein interactions withSARS-CoV-2, which has been determined to be the virus that causes COVID-19.

“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 [severe adult respiratory syndrome coronavirus 2] SARS-CoV-2,” Sharon Shacham, PhD, MBA, president and chief scientific officer, 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.”

SINE compounds have also demonstrated the ability to disrupt the replication of multiple viruses in vitro and in vivo. In addition, these compounds have been able to mediate anti-inflammatory and anti-viral effects in multiple animal models, including effects such as respiratory infections.

XPO1 inhibition has led to activity against more than 20 different viruses, such as RNA viruses, influenza, respiratory syncytial virus and other common causes of respiratory infection. Several assays have identified XPO1 inhibitors as having potential activity against SARS-CoV-2. However, data from animal models have not been available to date.

Marked pulmonary inflammation with high levels of cytokines, including IL6, IL1, IFNg, and others, has been 1 of the most important aspects of COVID-19. Selinexor and similar SINE compounds have potent anti-inflammatory activity through inhibition of Nuclear Factor kB (NF-kB), which causes reductions in all of these cytokines and may be particularly beneficial to patients with COVID-19.

Karyopharm does not expect the clinical program in COVID-19 to impact timing or prioritization of other key company milestones, including their planned submission of a supplemental New Drug Application (sNDA) for selinexor in combination with bortezomib (Velcade) and low-dose dexamethasone as second-line treatment of patients with relapsed/refractory multiple myeloma. The sNDA is based on data from the phase III BOSTON trial and remains on schedule for the second quarter of 2020.

“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,” said Shacham. “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.”

Karyopharm currently has a sufficient supply of the XPO1 inhibitor for both current and expected commercial supply for patients with multiple myeloma as well as for ongoing studies of patients with different cancers and those patients with COVID-19 enrolling in the clinical trial.

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Reference:

Karyopharm to Evaluate Low Dose Selinexor as a Potential Treatment for Hospitalized Patients with COVID-19 [news release]. Newton, MA: Karyopharm Therapeutics Inc.; April 7, 2020. https://bit.ly/2VftoVw. Accessed April 7, 2020.

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