• Combination of Once-Weekly XPOVIO® (seli­nexor), Once-Weekly Velcade® (bor­tez­o­mib) plus Dexa­meth­a­sone (SVd) Results in Statistically Significant Reduction in the Risk of Disease Pro­gression or Death Compared to Standard Twice-Weekly Velcade® plus Dexa­metha­sone (Vd) Regimen
• 47% Increase in Median PFS on SVd versus Vd
• Regulatory Submission Planned in 2Q 2020; Data to be Submitted for Presentation at Upcoming Medical Meetings
• Management to Host Conference Call Today at 8:30 AM ET

{{image}}Newton, MA (Press Release) – Karyo­pharm Thera­peutics Inc. (Nasdaq:KPTI), an on­col­ogy-focused pharma­ceu­tical com­pany, today announced pos­i­tive top-line results from the ran­dom­ized Phase 3 BOSTON study eval­u­ating once-weekly XPOVIO® (seli­nexor) in com­bi­na­tion with once-weekly Velcade® (bor­tez­o­mib) and low-dose dexa­meth­a­sone (SVd) com­pared to standard twice-weekly Velcade plus low-dose dexa­meth­a­sone (Vd) in patients with multiple myeloma who have re­ceived one to three prior lines of ther­apy. The BOSTON study met its pri­mary end­point of a statistically sig­nif­i­cant in­crease in pro­gres­sion-free sur­vival (PFS). The median PFS in the SVd arm was 13.93 months com­pared to 9.46 months in the Vd arm, rep­re­senting a 4.47 month (47%) in­crease in median PFS (hazard ratio=0.70; p=0.0066). There were no new safety signals on the SVd arm and there was no imbalance in deaths be­tween the two arms in the study. The full top-line data will be sub­mitted for pre­sen­ta­tion at upcoming medical meetings.

“We are thrilled to report these highly sig­nif­i­cant top-line results from the BOSTON study, the first ran­dom­ized Phase 3 trial to dem­onstrate clin­i­cally and statistically sig­nif­i­cant activity of once-weekly XPOVIO in com­bi­na­tion with a current standard of care treat­ment in patients with myeloma after one to three prior ther­a­pies,” said Sharon Shacham, PhD, MBA, Pres­i­dent and Chief Scientific Officer of Karyo­pharm. “In the study, patients on the SVd regi­men lived 47% longer without their dis­ease worsening, which we believe rep­re­sents an im­por­tant im­prove­ment in the treat­ment of patients with re­lapsed or re­frac­tory multiple myeloma. We plan to submit the full data set for pre­sen­ta­tions at upcoming medical meetings to share the results with the medical com­munity. We also in­tend to submit these data as quickly as possible to the U.S. Food and Drug Admin­istra­tion (FDA) as part of a supple­mental New Drug Application seek­ing to ex­pand the approved in­di­ca­tion for XPOVIO into second line treat­ment for patients with re­lapsed or re­frac­tory multiple myeloma. If approved, the SVd regi­men would be the first and only FDA-approved com­bi­na­tion drug regi­men that in­cludes once-weekly Velcade ther­apy for re­lapsed myeloma.”

XPOVIO re­ceived ac­cel­er­ated ap­­prov­al from the FDA on July 3, 2019 for the treat­ment of adult patients with re­lapsed or re­frac­tory multiple myeloma 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. This in­di­ca­tion is approved under ac­cel­er­ated ap­­prov­al based on re­sponse­ rate. Continued ap­­prov­al for this in­di­ca­tion may be contingent upon veri­fi­ca­tion and description of clin­i­cal benefit in a con­firmatory trial. Karyo­pharm ex­pec­ts to submit data from the Phase 3 BOSTON study to serve as this con­firmatory trial. The full Prescribing Information for XPOVIO is avail­able at www.XPOVIO.com.

About the BOSTON Study

BOSTON is a Phase 3 ran­dom­ized, active comparator-controlled, open-label, multi­center study that is designed to compare the efficacy, safety and cer­tain health-related quality of life (HR-QoL) parameters of once-weekly XPOVIO (seli­nexor) in com­bi­na­tion with once-weekly Velcade® (bor­tez­o­mib) plus low-dose dexa­meth­a­sone (SVd) versus twice-weekly Velcade plus low-dose dexa­meth­a­sone (Vd) in adult patients with re­lapsed or re­frac­tory multiple myeloma who have re­ceived one to three prior lines of ther­apy. The BOSTON study enrolled approx­i­mately 402 patients. The pri­mary end­point of the study is pro­gres­sion-free sur­vival (PFS) and key sec­ond­ary end­points in­clude over­all re­sponse­ rate (ORR), among others. Addi­tion­ally, the BOSTON study allows for patients on the Vd con­trol arm to crossover to the SVd arm fol­low­ing objective (quantitative) pro­gres­sion of dis­ease. The BOSTON study is being conducted at over 150 clin­i­cal sites inter­na­tionally.

Vd is a standard ther­apy for pre­vi­ously treated patients with multiple myeloma that is given by in­jec­tion twice-weekly. Unlike other drugs used to treat multiple myeloma, selinexor is taken orally. Patients ran­dom­ized to the SVd arm re­ceived selinexor (100mg once-weekly), Velcade (1.3 mg/m2 once-weekly given sub­cu­tane­ously) and dexa­meth­a­sone (40mg weekly). Patients ran­dom­ized to the Vd arm re­ceived Velcade® (twice-weekly) plus low-dose dexa­meth­a­sone (standard ther­apy given on the rec­om­mended schedule).

Conference Call Information

Karyopharm will host a conference call today, Monday, March 2, 2020, at 8:30 a.m. Eastern Time, to discuss the top-line results from the BOSTON study. To access the conference call, please dial (855) 437-4406 (local) or (484) 756-4292 (international) at least 10 min­utes prior to the start time and refer to conference 3515858. A live audio webcast of the call will be avail­able under "Events & Pre­sen­ta­tions" in the Investor section of the Com­pany's website, http://investors.karyopharm.com/events-presentations. An archived webcast will be avail­able on the Com­pany's website approx­i­mately two hours after the event.

About Multiple Myeloma

According to the National Cancer Institute (NCI), multiple myeloma is the second most common blood cancer in the U.S. with more than 32,000 new cases each year and over 130,000 patients living with the dis­ease. Despite recent thera­peutic ad­vances, there is cur­rently no cure and most patients’ dis­ease will typically progress fol­low­ing treat­ment with cur­rently avail­able ther­a­pies. According to the NCI, nearly 13,000 deaths due to multiple myeloma were ex­pec­ted in the U.S. in 2019.

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. A supple­mental New Drug Application was recently sub­mitted to the FDA seek­ing ac­cel­er­ated ap­­prov­al for selinexor as a new treat­ment for patients with re­lapsed or re­frac­tory diffuse large B-cell lym­phoma (DLBCL), and selinexor has re­ceived Fast Track and Orphan desig­na­tion from the FDA for this patient pop­u­la­tion. Selinexor is also being eval­u­ated in several other mid-and later-phase clin­i­cal trials across multiple cancer in­di­ca­tions, in­clud­ing in multiple myeloma in a pivotal, ran­dom­ized Phase 3 study in com­bi­na­tion with Velcade® (bor­tez­o­mib) and low-dose dexa­meth­a­sone (BOSTON), as a poten­tial back­bone ther­apy in com­bi­na­tion with approved 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.

IMPORTANT SAFETY INFORMATION

Thrombocytopenia

XPOVIO can cause thrombo­cyto­penia, leading to poten­tially fatal hemorrhage. Thrombocytopenia was reported as an adverse reac­tion in 74% of patients, and severe (Grade 3-4) thrombo­cyto­penia occurred in 61% of patients treated with XPOVIO. The median time to onset of the first event was 22 days. Bleeding occurred in 23% of patients with thrombo­cyto­penia, clin­i­cally sig­nif­i­cant bleeding occurred in 5% of patients with thrombo­cyto­penia and fatal hemorrhage occurred in <1% of patients.

Monitor platelet counts at base­line, during treat­ment, and as clin­i­cally in­di­cated. Monitor more fre­quently during the first two 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 and/or reduce dose, or perma­nently dis­con­tinue based on severity of adverse reac­tion.

Neutropenia

XPOVIO can cause neu­tro­penia, poten­tially in­creas­ing the risk of in­fec­tion. Neutropenia was reported as an adverse reac­tion in 34% of patients, and severe (Grade 3-4) neu­tro­penia occurred in 21% of patients treated with XPOVIO. The median time to onset of the first event was 25 days. Febrile neu­tro­penia was reported in 3% of patients.

Obtain neu­tro­phil counts at base­line, during treat­ment, and as clin­i­cally in­di­cated. Monitor more fre­quently during the first two months of treat­ment. Monitor patients for signs and symp­toms of con­com­i­tant in­fec­tion and eval­u­ate promptly. Consider sup­port­ive measures in­clud­ing antimicrobials for signs of in­fec­tion and use of growth factors (e.g., G-CSF). Interrupt and/or reduce dose, or perma­nently dis­con­tinue based on severity of adverse reac­tion.

Gastrointestinal Toxicity

Gastrointestinal toxicities occurred in patients treated with XPOVIO.

Nausea / Vomiting

Nausea was reported as an adverse reac­tion in 72% of patients, and Grade 3 nausea occurred in 9% of patients treated with XPOVIO. The median time to onset of the first nausea event was 3 days.

Vomiting was reported in 41% of patients, and Grade 3 vomiting occurred in 4% of patients treated with XPOVIO. The median time to onset of the first vomiting event was 5 days.

Provide pro­phy­lactic 5-HT3 antagonists and/or other anti-nausea agents, prior to and during treat­ment with XPOVIO. Manage nausea/vomiting by dose inter­rup­tion, re­duc­tion, and/or dis­con­tinu­a­tion. Ad­min­­ister in­tra­venous fluids and replace electrolytes to prevent dehydration in patients at risk. Use addi­tional anti-nausea med­i­ca­tions as clin­i­cally in­di­cated.

Diarrhea

Diarrhea was reported as an adverse reac­tion in 44% of patients, and Grade 3 diarrhea occurred in 6% of patients treated with XPOVIO. The median time to onset of diarrhea was 15 days.

Manage diarrhea by dose modifications and/or standard anti-diarrheal agents; admin­ister in­tra­venous fluids to prevent dehydration in patients at risk.

Anorexia/Weight Loss

Anorexia was reported as an adverse reac­tion in 53% of patients, and Grade 3 anorexia occurred in 5% of patients treated with XPOVIO. The median time to onset of anorexia was 8 days.

Weight loss was reported as an adverse reac­tion in 47% of patients, and Grade 3 weight loss occurred in 1% of patients treated with XPOVIO. The median time to onset of weight loss was 15 days.

Monitor patient weight at base­line, during treat­ment, and as clin­i­cally in­di­cated. Monitor more fre­quently during the first two months of treat­ment. Manage anorexia and weight loss with dose modifications, appetite stimulants, and nutritional sup­port.

Hyponatremia

XPOVIO can cause hyponatremia; 39% of patients treated with XPOVIO ex­peri­enced hyponatremia, 22% of patients ex­peri­enced Grade 3 or 4 hyponatremia. The median time to onset of the first event was 8 days.

Monitor sodium level at base­line, during treat­ment, and as clin­i­cally in­di­cated. Monitor more fre­quently during the first two months of treat­ment. Correct sodium levels for concurrent hyperglycemia (serum glucose >150 mg/dL) and high serum paraprotein levels. Treat hyponatremia per clin­i­cal guidelines (intravenous saline and/or salt tablets), in­clud­ing dietary review. Interrupt and/or reduce dose, or perma­nently dis­con­tinue based on severity of adverse reac­tion.

Infections

In patients re­ceiv­ing XPOVIO, 52% of patients ex­peri­enced any grade of in­fec­tion. Upper res­pira­tory tract in­fec­tion of any grade occurred in 21%, pneu­monia in 13%, and sepsis in 6% of patients. Grade ≥3 in­fec­tions were reported in 25% of patients, and deaths resulting from an in­fec­tion occurred in 4% of patients. The most commonly reported Grade ≥3 in­fec­tions were pneu­monia in 9% of patients, followed by sepsis in 6%. The median time to onset was 54 days for pneu­monia and 42 days for sepsis. Most in­fec­tions were not asso­ci­ated with neu­tro­penia and were caused by non-opportunistic organisms.

Neurological Toxicity

Neurological toxicities occurred in patients treated with XPOVIO.

Neurological adverse reac­tions in­clud­ing dizzi­ness, syncope, depressed level of consciousness, and mental status changes (including delirium and confusional state) occurred in 30% of patients, and severe events (Grade 3-4) occurred in 9% of patients treated with XPOVIO. Median time to the first event was 15 days.

Optimize hydration status, hemoglobin level, and con­com­i­tant med­i­ca­tions to avoid exacerbating dizzi­ness or mental status changes.

Embryo-Fetal Toxicity

Based on data from animal studies and its mech­a­nism of action, XPOVIO can cause fetal harm when admin­istered to a pregnant woman. Selinexor admin­istra­tion to pregnant animals during or­gano­gen­e­sis resulted in structural ab­nor­mal­i­ties and alterations to growth at exposures below those occurring clin­i­cally at the rec­om­mended dose.

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 (incidence ≥20%) are thrombo­cyto­penia, fatigue, nausea, anemia, de­creased appetite, de­creased weight, diarrhea, vomiting, hyponatremia, neu­tro­penia, leu­ko­penia, con­sti­pa­tion, dyspnea, and upper res­pira­tory tract in­fec­tion.

The treat­ment dis­con­tinu­a­tion rate due to adverse reac­tions was 27%; 53% of patients had a re­duc­tion in the XPOVIO dose, and 65.3% had the dose of XPOVIO interrupted. The most fre­quent adverse reac­tions requiring perma­nent dis­con­tinu­a­tion in 4% or greater of patients who re­ceived XPOVIO in­cluded fatigue, nausea, and thrombo­cyto­penia. The rate of fatal adverse reac­tions was 8.9%.

Please see XPOVIO Full Prescribing Information avail­able at www.XPOVIO.com.

About Karyo­pharm Thera­peutics

Karyopharm Thera­peutics Inc. (Nasdaq: KPTI) is an on­col­ogy-focused 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 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 FDA in July 2019 in com­bi­na­tion with dexa­meth­a­sone as a treat­ment for patients with heavily pre­treated multiple myeloma. An MAA for selinexor is also cur­rently under review by the EMA for the same in­di­ca­tion. The Com­pany recently sub­mitted a New Drug Application to the FDA seek­ing ap­­prov­al for XPOVIO in patients with DLBCL. 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 relating to XPOVIO for the treat­ment of patients with heavily pre­treated 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; sub­missions to, and the review and poten­tial ap­­prov­al of selinexor by, regu­la­tory author­i­ties, in­clud­ing the antic­i­pated avail­a­bil­ity of data to sup­port such sub­missions, timing of such sub­missions and actions by regu­la­tory author­i­ties and 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 con­di­tional ap­­prov­al in the E.U. as a result of data from the STORM study or con­firmatory ap­­prov­al in the U.S. or EU based on the BOSTON study in patients with re­lapsed or re­frac­tory multiple myeloma, or ac­cel­er­ated ap­­prov­al in the U.S. for patients with re­lapsed or re­frac­tory DLBCL as a result of data from the SADAL study, or that any of Karyo­pharm's drug can­di­dates, in­clud­ing selinexor, will suc­cess­fully com­plete nec­es­sary clin­i­cal devel­op­ment phases or that devel­op­ment of any of Karyo­pharm's drug can­di­dates will con­tinue. 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: 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 dis­eases 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 Annual Report on Form 10-K for the year ended De­cem­ber 31, 2019, which was filed with the Se­cu­ri­ties and Ex­change Com­mis­sion (SEC) on Feb­ru­ary 26, 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.