Candidate: XPOVIO® (selinexor)
Type: First-in-class, oral selective inhibitor of nuclear export (SINE), designed to block the cellular protein XPO1. Selinexor was granted FDA accelerated approval in July 2019 in combination with dexamethasone as a treatment for some adults with relapsed refractory multiple myeloma.
Status: Karyopharm said April 20 the first patient was dosed in a randomized, multi-center, placebo-controlled Phase II trial (NCT04349098) designed to assess the activity and safety of 20mg of selinexor given orally three times a week for two weeks in patients with severe COVID-19. The trial is expected to enroll approximately 230 patients at clinical sites in the U.S., Europe, and Israel.
The study’s primary endpoint, according to Karyopharm, is time to clinical improvement based on improvement in the Ordinal Scale, consistent with COVID-19 trial recommendations by the FDA and World Health Organization (WHO). Additional secondary endpoints in the study include the overall death rate at day 28 as well as the rate of, and time to, mechanical ventilation.
Karyopharm has noted that SINE compounds have been shown to disrupt the replication of multiple viruses in vitro and in vivo, and to mediate anti-inflammatory and anti-viral effects, including respiratory infections, in several animal models. Karyopharm cited a preprint study published March 20 in bioRxiv identifying SINE compounds as having the potential to interfere with key host protein interactions with SARS-CoV-2.
The company said it is still on track to submit a supplemental NDA to the FDA 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 III trial (NCT03110562), for which Karyopharm announced positive topline results in March.
COVID-19: 200 Candidates and Counting
To navigate through the >200 potential therapeutic and vaccine options for COVID-19, GEN has grouped the candidates into four broad categories based on their developmental and (where applicable) clinical progress:
● FRONT RUNNER – the most promising therapeutics/vaccines based on clinical progress, favorable data or both.
● DEFINITELY MAYBE – earlier phases with promising partners, or more advanced candidates in development that have generated uneven data
● KEEPING AN EYE ON… – interesting technology, attracting notable partners, or both, but preliminary data.
● TOO SOON TO TELL – longshots pending additional experimental and/or clinical data.
GEN has also tagged the most common treatment types:
● ANTIVIRAL
● VAX
● ANTIBODY
● RNA
