− Encouraging Anti-Viral and Anti-Inflammatory Activity Demonstrated in a Subset of Patients in a Study of Low Dose Selinexor in Hospitalized Patients with Severe COVID-19 −
− A Case Report From a COVID-19 Patient Treated with Selinexor Now Also Published in the Annals of Case Reports -
NEWTON, Mass., Oct. 6, 2020 /PRNewswire/ -- Karyopharm Therapeutics Inc. (Nasdaq: KPTI), a commercial-stage pharmaceutical company pioneering novel cancer therapies, today announced an oral presentation at the International Society for Influenza and Other Respiratory Virus Diseases Antiviral Group (ISIRV-AVG) Virtual Conference on Therapeutics for COVID-19 taking place from October 6 - 8, 2020. The presentation will feature data from a Phase 2 clinical study evaluating low dose oral selinexor in hospitalized patients with severe COVID-19 (NCT04349098).
While an interim analysis indicated that the trial was unlikely to meet its pre-specified primary endpoint across the entire patient population studied, and has since been discontinued, the results demonstrated encouraging anti-viral and anti-inflammatory activity in an important subset of treated patients. The randomized, multi-center, placebo-controlled Phase 2 study was designed to assess the activity and safety of 20mg of selinexor given orally three times a week for two weeks, a dosing level significantly lower than the U.S. Food and Drug Administration (FDA) approved dose of selinexor, marketed as XPOVIO®, to treat patients with relapsed or refractory multiple myeloma or relapsed or refractory diffuse large B-cell lymphoma.
A post-hoc analysis of 66 patients with either baseline serum lactate dehydrogenase (LDH) ≤370 U/L or D-dimer ≤600 mcg/L FEU (Low LDH/DD) showed that treatment with selinexor (n=38) compared to placebo (n=28) was associated with a significantly higher percentage of patients discharged by Day 14 (78.9% vs 57.1%; p=0.029) with a trend towards superior ≥2-point improvement in the Ordinal Scale (OSI-2) on Day 14 (78.9% vs 64.3%; p=0.095). Additionally, a positive trend was observed in patients treated with selinexor to convert to a negative COVID-19 PCR test as compared to placebo (42.1% vs 28.6%; p=0.13) and a significant reduction in IL1-RA, IL-6, IL-7, IP-10, and TNF-a levels, measurements of inflammation, was also seen within eight days of selinexor treatment (p150 mg/dL) and high serum paraprotein levels. Assess hydration status and manage hyponatremia per clinical guidelines, including intravenous saline and/or salt tablets as appropriate and dietary review. Interrupt, reduce dose, or permanently discontinue based on severity of the AR.
Serious Infection: XPOVIO can cause serious and fatal infections. Most infections were not associated with Grade 3 or higher neutropenia. Atypical infections reported after taking XPOVIO include, but are not limited to, fungal pneumonia and herpesvirus infection.
Monitor for signs and symptoms of infection, and evaluate and treat promptly.
Neurological Toxicity: XPOVIO can cause life-threatening neurological toxicities.
Coadministration of XPOVIO with other products that cause dizziness or mental status changes may increase the risk of neurological toxicity.
Advise patients to refrain from driving and engaging in hazardous occupations or activities, such as operating heavy or potentially dangerous machinery, until the neurological toxicity fully resolves. Optimize hydration status, hemoglobin level, and concomitant medications to avoid exacerbating dizziness or mental status changes. Institute fall precautions as appropriate.
Embryo-Fetal Toxicity: XPOVIO can cause fetal harm when administered to a pregnant woman.
Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential and males with a female partner of reproductive potential to use effective contraception during treatment with XPOVIO and for 1 week after the last dose.
ADVERSE REACTIONSThe most common adverse reactions (ARs) in ≥20% of patients with MM are thrombocytopenia, fatigue, nausea, anemia, decreased appetite, decreased weight, diarrhea, vomiting, hyponatremia, neutropenia, leukopenia, constipation, dyspnea, and upper respiratory tract infection.
The most common ARs, excluding laboratory abnormalities, in ≥20% of patients with DLBCL are fatigue, nausea, diarrhea, appetite decrease, weight decrease, constipation, vomiting, and pyrexia. Grade 3-4 laboratory abnormalities in ≥15% of patients included thrombocytopenia, lymphopenia, neutropenia, anemia, and hyponatremia. Grade 4 laboratory abnormalities in ≥5% were thrombocytopenia, lymphopenia, and neutropenia.
In patients with MM, fatal ARs occurred in 9% of patients. Serious ARs occurred in 58% of patients. Treatment discontinuation rate due to ARs was 27%. The most frequent ARs requiring permanent discontinuation in ≥4% of patients included fatigue, nausea, and thrombocytopenia.
In patients with DLBCL, fatal ARs occurred in 3.7% of patients within 30 days, and 5% of patients within 60 days of last treatment; the most frequent fatal AR was infection (4.5% of patients). Serious ARs occurred in 46% of patients; the most frequent serious AR was infection. Discontinuation due to ARs occurred in 17% of patients.
USE IN SPECIFIC POPULATIONSIn MM, no overall difference in effectiveness of XPOVIO was observed in patients >65 years old when compared with younger patients. Patients ≥75 years old had a higher incidence of discontinuation due to an AR than younger patients, a higher incidence of serious ARs, and a higher incidence of fatal ARs.
Clinical studies in patients with relapsed or refractory DLBCL did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger patients.
The effect of end-stage renal disease (CLCR