Newton, MA (Press Release) – Karyo­pharm Thera­peutics Inc. (Nasdaq:KPTI), an inno­va­tion-driven pharma­ceu­tical com­pany, to­day an­nounced that the U.S. Food and Drug Admin­istra­tion (FDA) has ac­cepted for filing its supple­mental New Drug Appli­ca­tion (sNDA) seek­ing ap­prov­al for XPOVIO^® (seli­nexor), its first-in-class, oral Sel­ective Inhibitor of Nuclear Export (SINE) com­pound, as a new treat­ment for patients with mul­ti­ple myeloma after at least one prior line of ther­apy. Karyo­pharm ex­pects a de­ci­sion from the FDA re­gard­ing this sNDA before the end of the first quarter of 2021.

“This sNDA ac­ceptance brings us one step closer to providing access to XPOVIO for a sig­nif­i­cantly larger patient pop­u­la­tion battling mul­ti­ple myeloma,” said Sharon Shacham, PhD, MBA, Founder, Pres­i­dent and Chief Scientific Of­fi­cer of Karyo­pharm. “If approved, we be­lieve XPOVIO will be­come an im­por­tant new, oral, once-weekly treat­ment op­tion, used in com­bi­na­tion with once-weekly Vel­cade^®, for patients with mul­ti­ple myeloma after at least one prior line of ther­apy. We look for­ward to work­ing closely with the FDA during their re­­view process and we sincerely thank the many patients, care­givers and physicians whose immense con­tri­bu­tions have helped us achieve this latest mile­stone.”

XPOVIO has been pre­vi­ously approved by the FDA for the treat­ment of patients with penta-refractory mul­ti­ple myeloma and re­lapsed or re­frac­tory diffuse large B-cell lym­phoma. Provided mar­ket­ing ap­prov­al is granted by the FDA for this third on­col­ogy in­di­ca­tion, Karyo­pharm plans to con­tinue to com­mer­cial­ize XPOVIO in the U.S. using its existing com­mer­cial infrastructure. The Com­pany also plans to submit a Marketing Authori­za­tion Appli­ca­tion to the Euro­pean Medicines Agency later this year for this same in­di­ca­tion.

About XPOVIO^® (seli­nexor)

XPOVIO is a first-in-class, oral Sel­ective Inhibitor of Nuclear Export (SINE) com­pound. XPOVIO functions by sel­ectively binding to and in­hib­iting the nuclear export pro­tein exportin 1 (XPO1, also called CRM1). XPOVIO blocks the nuclear export of tumor sup­pressor, growth regu­la­tory and anti-in­flam­ma­tory pro­teins, lead­ing to accumulation of these pro­teins in the nucleus and enhancing their anti-cancer ac­­tiv­ity in the cell. The forced nuclear retention of these pro­teins can coun­ter­act a mul­ti­tude of the oncogenic path­ways that, unchecked, allow cancer cells with severe DNA damage to con­tinue to grow and divide in an unrestrained fashion. Karyo­pharm re­ceived ac­cel­er­ated U.S. Food and Drug Admin­istra­tion (FDA) ap­prov­al of XPOVIO in July 2019 in com­bi­na­tion with dexa­meth­a­sone for the treat­ment of adult patients with re­lapsed re­frac­tory mul­ti­ple myeloma (RRMM) who have re­ceived at least four prior ther­a­pies and whose dis­ease is re­frac­tory to at least two pro­te­a­some in­hib­i­tors, at least two immuno­modu­la­tory agents, and an anti-CD38 mono­clonal anti­body. Karyo­pharm has also sub­mitted a Marketing Authori­za­tion Appli­ca­tion (MAA) to the Euro­pean Medicines Agency (EMA) with a re­quest for con­di­tional ap­prov­al of selinexor in this same RRMM in­di­ca­tion. Karyo­pharm’s supple­mental New Drug Appli­ca­tion (sNDA) re­quest­ing an ex­pan­sion of its cur­rent in­di­ca­tion to in­clude the treat­ment for patients with mul­ti­ple myeloma after at least one prior line of ther­apy has been ac­cepted for filing by the FDA. In June 2020, Karyo­pharm re­ceived ac­cel­er­ated FDA ap­prov­al of XPOVIO for its sec­ond in­di­ca­tion in adult patients with re­lapsed or re­frac­tory diffuse large B-cell lym­phoma (DLBCL), not other­wise specified, in­clud­ing DLBCL arising from follicular lym­phoma, after at least 2 lines of sys­temic ther­apy. Selinexor is also being eval­u­ated in sev­er­al other mid-and later-phase clin­i­cal trials across mul­ti­ple cancer in­di­ca­tions, in­clud­ing as a po­ten­tial back­bone ther­apy in com­bi­na­tion with approved myeloma ther­a­pies (STOMP), in liposarcoma (SEAL) and in endometrial cancer (SIENDO), among others. Addi­tional Phase 1, Phase 2 and Phase 3 stud­ies are on­go­ing or cur­rently planned, in­clud­ing mul­ti­ple stud­ies in com­bi­na­tion with approved ther­a­pies in a variety of tumor types to fur­ther in­form Karyo­pharm’s clin­i­cal de­vel­op­ment priorities for selinexor. Addi­tional clin­i­cal trial in­for­ma­tion for selinexor is avail­able at www.clinicaltrials.gov.

For more in­for­ma­tion about Karyo­pharm’s prod­ucts or clin­i­cal trials, please contact the Medical In­for­ma­tion ­de­part­ment at:

Tel: +1 (888) 209-9326
Email: med­i­calinformation@karyopharm.com

IMPORTANT SAFETY INFORMATION

Thrombocytopenia: XPOVIO can cause life-threatening thrombo­cyto­penia, po­ten­tially lead­ing to hemorrhage. Thrombocytopenia was re­ported in patients with mul­ti­ple myeloma (MM) and devel­oped or worsened in patients with DLBCL.

Thrombocytopenia is the lead­ing cause of dosage mod­i­fi­ca­tions. Monitor platelet counts at base­line and through­out treat­ment. Monitor more fre­quently during the first 3 months of treat­ment. In­sti­tute platelet transfusion and/or other treat­ments as clin­i­cally in­di­cated. Monitor patients for signs and symp­toms of bleeding and eval­u­ate promptly. Interrupt, reduce dose, or per­ma­nently dis­con­tinue based on se­ver­i­ty of ad­verse reac­tion.

Neutropenia: XPOVIO can cause life-threatening neu­tro­penia, po­ten­tially in­creas­ing the risk of in­fec­tion. Neutropenia and febrile neu­tro­penia oc­curred in patients with MM and in patients with DLBCL.

Obtain white blood cell counts with dif­fer­en­tial at base­line and through­out treat­ment. Monitor more fre­quently during the first 3 months of treat­ment. Monitor patients for signs and symp­toms of con­com­i­tant in­fec­tion and eval­u­ate promptly. Consider sup­port­ive measures, in­clud­ing antimicrobials and growth factors (e.g., G-CSF). Interrupt, reduce dose, or per­ma­nently dis­con­tinue based on se­ver­i­ty of ad­verse reac­tion (AR).

Gastrointestinal Toxicity: XPOVIO can cause severe gastro­in­tes­ti­nal toxicities in patients with MM and DLBCL.

Nausea/Vomiting: Provide pro­phy­lactic antiemetics. Ad­min­ister 5-HT3 re­cep­tor antagonists and other anti-nausea agents prior to and during treat­ment with XPOVIO. Interrupt, reduce dose, or per­ma­nently dis­con­tinue based on se­ver­i­ty of ARs. Ad­min­ister in­tra­venous fluids to prevent dehydration and re­place elec­tro­lytes as clin­i­cally in­di­cated.

Diarrhea: Interrupt, reduce dose, or per­ma­nently dis­con­tinue based on se­ver­i­ty of ARs. Provide stan­dard anti-diarrheal agents, admin­ister in­tra­venous fluids to prevent dehydration, and re­place elec­tro­lytes as clin­i­cally in­di­cated.

Anorexia/Weight Loss: Monitor weight, nutritional status, and volume status at base­line and through­out treat­ment. Monitor more fre­quently during the first 3 months of treat­ment. Interrupt, reduce dose, or per­ma­nently dis­con­tinue based on se­ver­i­ty of ARs. Provide nutritional sup­port, fluids, and elec­tro­lyte repletion as clin­i­cally in­di­cated.

Hyponatremia: XPOVIO can cause severe or life-threatening hyponatremia. Hyponatremia devel­oped in patients with MM and in patients with DLBCL.

Monitor sodium level at base­line and through­out treat­ment. Monitor more fre­quently during the first 2 months of treat­ment. Correct sodium levels for concurrent hyperglycemia (serum glucose > 150 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 REACTIONS

The 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 POPULATIONS

In 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

Please see full Prescribing In­for­ma­tion.

To re­port SUSPECTED ADVERSE REACTIONS, contact Karyo­pharm Thera­peutics Inc. at 1-888-209-9326 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

About Karyo­pharm Thera­peutics

Karyopharm Thera­peutics Inc. (Nasdaq: KPTI) is an inno­va­tion-driven pharma­ceu­tical com­pany ded­i­cated to the dis­cov­ery, de­vel­op­ment, and com­mer­cial­i­za­tion of novel first-in-class drugs directed against nuclear export and re­lated targets for the treat­ment of cancer and other major dis­eases. Karyo­pharm's Sel­ective Inhibitor of Nuclear Export (SINE) com­pounds function by binding with and in­hib­iting the nuclear export pro­tein XPO1 (or CRM1). Karyo­pharm’s lead com­pound, XPOVIO^® (seli­nexor), re­ceived ac­cel­er­ated ap­prov­al from the U.S. Food and Drug Admin­istra­tion (FDA) in July 2019 in com­bi­na­tion with dexa­meth­a­sone as a treat­ment for patients with heavily pre­treated mul­ti­ple myeloma. In June 2020, XPOVIO was approved by the FDA as a treat­ment for patients with re­lapsed or re­frac­tory diffuse large B-cell lym­phoma. A Marketing Authori­za­tion Appli­ca­tion for selinexor for patients with heavily pre­treated mul­ti­ple myeloma is also cur­rently under re­­view by the Euro­pean Medicines Agency. In addi­tion to single-agent and com­bi­na­tion ac­­tiv­ity against a variety of human cancers, SINE com­pounds have also shown bio­logical ac­­tiv­ity in models of neu­ro­de­gen­er­a­tion, inflammation, auto­immune dis­ease, cer­tain viruses and wound-healing. Karyo­pharm has sev­er­al inves­ti­ga­tional pro­grams in clin­i­cal or pre­clin­i­cal de­vel­op­ment. For more in­for­ma­tion, please visit www.karyopharm.com.

Forward-Looking State­ments

This press re­lease con­tains for­ward-looking state­ments within the meaning of The Private Se­cu­ri­ties Lit­i­ga­tion Reform Act of 1995. Such for­ward-looking state­ments in­clude those re­gard­ing Karyo­pharm’s ex­pec­ta­tions re­lated to XPOVIO for the treat­ment of mul­ti­ple myeloma or re­lapsed or re­frac­tory diffuse large B-cell lym­phoma; com­mer­cial­i­za­tion of XPOVIO or any of its drug can­di­dates and the com­mer­cial per­for­mance of XPOVIO; regu­la­tory sub­missions to, and the re­­view and po­ten­tial ap­prov­al of selinexor by, regu­la­tory author­i­ties, in­clud­ing the antic­i­pated timing of such sub­missions, the antic­i­pated avail­a­bil­ity of data to sup­port such sub­missions, the po­ten­tial avail­a­bil­ity of ac­cel­er­ated ap­prov­al path­ways, and the thera­peutic po­ten­tial of and po­ten­tial clin­i­cal de­vel­op­ment plans for Karyo­pharm's drug can­di­dates, especially selinexor. . Such state­ments are subject to nu­mer­ous im­por­tant factors, risks and un­cer­tainties, many of which are beyond Karyo­pharm's con­trol, that may cause actual events or re­­sults to differ ma­teri­ally from Karyo­pharm's cur­rent ex­pec­ta­tions. For example, there can be no guar­an­tee that Karyo­pharm will suc­cess­fully com­mer­cial­ize XPOVIO; that regulators will agree that selinexor qualifies for ac­cel­er­ated ap­prov­al in the U.S. or con­di­tional ap­prov­al in the E.U. as a re­­sult of the data from the BOSTON study in patients with mul­ti­ple myeloma after at least one prior line of ther­apy or that any of Karyo­pharm's drug can­di­dates, in­clud­ing selinexor, will suc­cess­fully com­plete nec­es­sary clin­i­cal de­vel­op­ment phases. Fur­ther, there can be no guar­an­tee that any pos­i­tive de­vel­op­ments in the de­vel­op­ment or com­mer­cial­i­za­tion of Karyo­pharm’s drug can­di­date port­folio will re­­sult in stock price ap­pre­ci­a­tion. Man­age­ment’s ex­pec­ta­tions and, there­fore, any for­ward-looking state­ments in this press re­lease could also be affected by risks and un­cer­tainties relating to a num­ber of other factors, in­clud­ing the fol­low­ing: the risk that the COVID-19 pan­dem­ic could disrupt Karyo­pharm’s business more severely than it cur­rently antic­i­pates, in­clud­ing by reducing sales of XPOVIO, in­ter­rupt­ing or delaying re­search and de­vel­op­ment efforts, im­pacting the ability to procure suf­fi­cient supply for the de­vel­op­ment and com­mer­cial­i­za­tion of selinexor or other prod­uct can­di­dates, delaying on­go­ing or planned clin­i­cal trials, im­ped­ing the execution of business plans, planned regu­la­tory mile­stones and timelines, or in­con­ve­nienc­ing patients; the adoption of XPOVIO in the com­mer­cial mar­ket­place, the timing and costs in­volved in com­mer­cial­iz­ing XPOVIO or any of Karyo­pharm’s drug can­di­dates that re­ceive regu­la­tory ap­prov­al; the ability to retain regu­la­tory ap­prov­al of XPOVIO or any of Karyo­pharm’s drug can­di­dates that re­ceive regu­la­tory ap­prov­al; Karyo­pharm's re­­sults of clin­i­cal trials and pre­clin­i­cal stud­ies, in­clud­ing sub­se­quent analysis of existing data and new data re­ceived from on­go­ing and future stud­ies; the content and timing of de­ci­sions made by the U.S. Food and Drug Admin­istra­tion and other regu­la­tory author­i­ties, inves­ti­ga­tional re­­view boards at clin­i­cal trial sites and pub­li­ca­tion re­­view bodies, in­clud­ing with respect to the need for addi­tional clin­i­cal stud­ies; the ability of Karyo­pharm or its third party col­lab­o­rators or successors in interest to fully per­form their re­spec­tive obli­ga­tions under the appli­cable agree­ment and the po­ten­tial future fi­nan­cial implications of such agree­ment; Karyo­pharm's ability to obtain and main­tain requisite regu­la­tory ap­prov­als and to en­roll patients in its clin­i­cal trials; unplanned cash re­quire­ments and ex­pen­di­tures; de­vel­op­ment of drug can­di­dates by Karyo­pharm’s com­pet­i­tors for in­di­ca­tions in which Karyo­pharm is cur­rently devel­op­ing its drug can­di­dates; and Karyo­pharm’s ability to obtain, main­tain and enforce pat­ent and other in­tel­lec­tual prop­er­ty pro­tec­tion for any drug can­di­dates it is devel­op­ing. These and other risks are described under the cap­tion "Risk Factors" in Karyo­pharm’s Quar­ter­ly Report on Form 10-Q for the quarter ended March 31, 2020, which was filed with the Se­cu­ri­ties and Ex­change Com­mis­sion (SEC) on May 5, 2020, and in other filings that Karyo­pharm may make with the SEC in the future. Any for­ward-looking state­ments con­tained in this press re­lease speak only as of the date hereof, and, except as re­quired by law, Karyo­pharm expressly disclaims any obli­ga­tion to up­date any for­ward-looking state­ments, whether as a re­­sult of new in­for­ma­tion, future events or other­wise.

Velcade^® is a registered trademark of Takeda Pharma­ceu­tical Com­pany Limited.

Source: Karyo­pharm Thera­peutics.