Newton, MA (Press Release) – Karyopharm Therapeutics Inc. (Nasdaq:KPTI), a clin­i­cal-stage phar­ma­ceu­tical com­pany, today announced that the U.S. Food and Drug Admin­istra­tion (FDA) Onco­logic Drugs Advisory Committee (ODAC) met to discuss the New Drug Application (NDA) for selinexor, a first-in-class, oral Selective Inhibitor of Nuclear Export (SINE) com­­pound. The NDA, which is cur­rently under Priority Review by the FDA, is seeking accelerated approval for selinexor in com­bi­na­tion with dexa­meth­a­sone for the treat­ment of patients with re­lapsed refractory multiple myeloma who have received at least three prior ther­a­pies and whose disease is refractory to at least one pro­te­a­some inhibitor (PI), one immuno­modu­la­tory agent (IMiD), and one anti-CD38 mono­clonal anti­body.

The ODAC voted 8 to 5 rec­om­mending that the FDA wait for the results from Karyopharm’s ran­dom­ized, open-label, Phase 3 BOSTON study eval­u­ating selinexor in patients with re­lapsed or refractory multiple myeloma, before making a final de­ci­sion re­gard­ing approval. The BOSTON study is eval­u­ating selinexor in com­bi­na­tion with Velcade® (bor­tez­o­mib) and low-dose dexa­meth­a­sone com­pared to bor­tez­o­mib and low-dose dexa­meth­a­sone in patients with multiple myeloma who have had one to three prior lines of ther­apy. Importantly, in the selinexor arm of the study, both selinexor and bor­tez­o­mib are admin­istered once per week while in the control arm, bor­tez­o­mib is admin­istered at its cur­rently indicated, twice per week schedule. Patient enrollment in the BOSTON study is now com­plete and top-line data are ex­pec­ted by the end of 2019 at the earliest, or into 2020, pending pro­gres­sion-free survival (PFS) events, a pri­mary end­point in this trial.

“While we are disappointed with ODAC’s recom­men­da­tion to delay the poten­tial approval of selinexor, we plan to work with the FDA to eval­u­ate the best path for­ward as they con­tinue to review our NDA. Karyopharm remains committed to improv­ing the out­comes of patients with cancer, in­­clud­ing those with re­lapsed refractory multiple myeloma,” said Sharon Shacham, PhD, MBA, Founder, Pres­i­dent and Chief Scientific Officer of Karyopharm. “Patients with triple class refractory multiple myeloma have disease which has progressed fol­low­ing treat­ment with the most effective myeloma drugs approved to date and are in desperate need of new treat­ment options. Karyopharm has assembled and submitted a compelling, com­pre­hen­sive clin­i­cal data package to the FDA sup­porting the request for accelerated approval for selinexor. We are committed to work­ing with the FDA, patients, and the myeloma com­munity with the goal to provide selinexor as an option for those patients with no other options of known clin­i­cal benefit.”

The ODAC is an independent panel of experts that eval­u­ates data con­cern­ing the efficacy and safety of mar­keted and inves­ti­ga­tional prod­ucts for use in the treat­ment of cancer and makes appro­pri­ate recom­men­da­tions to the FDA. Although the FDA will con­sider the recom­men­da­tion of the panel, the final de­ci­sion regard­ing the approval of the prod­uct is made by the FDA solely, and the recom­men­da­tions by the panel are non-binding.

Karyopharm’s NDA seeking accelerated approval for oral selinexor in com­bi­na­tion with dexa­meth­a­sone as a treat­ment for patients with triple class refractory multiple myeloma who have received at least three prior ther­a­pies is under Priority Review by the FDA with an action date of April 6, 2019 under the Prescription Drug User-Fee Act (PDUFA).

The selinexor NDA is sup­ported by data from Karyopharm’s Phase 2b STORM (Selinexor Treatment of Refractory Myeloma) study, which eval­u­ated selinexor and low-dose dexa­meth­a­sone in 122 heavily pre­treated patients with triple class refractory multiple myeloma who have been pre­vi­ously exposed to all five of the most commonly prescribed anti-myeloma ther­a­pies cur­rently avail­able. The study met its pri­mary objective with an over­all response rate (ORR) of 26.2%, which in­cluded two stringent com­plete responses (sCRs), six very good partial responses (VGPRs) and 24 partial responses (PRs). The most common adverse events in­cluded thrombo­cytopenia, nausea/vomiting, fatigue and de­creased appetite. Adverse events were generally predictable and man­ageable with dose ad­just­ments and treat­ment-emergent AEs leading to treat­ment dis­con­tinu­a­tion occurred in 26.8% of patients, and these were con­sidered by the In­ves­ti­ga­tor to be treat­ment-related in 17.9% of patients. Major organ toxicities were not prominent in this study and safety results were con­sis­tent with those pre­vi­ously reported from Part 1 of this STORM study (Vogl et al., J Clin Oncol, 2018) and from other selinexor studies.

The Company has also submitted a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) for selinexor requesting con­di­tional approval for the treat­ment of patients with re­lapsed refractory multiple myeloma who have received at least three prior lines of ther­apy and whose disease is refractory to at least one PI, one IMiD, and one anti-CD38 mono­clonal anti­body. The selinexor MAA has been granted accelerated assess­ment by the EMA’s Committee for Medicinal Products for Human Use.

Karyopharm will discuss ODAC’s recom­men­da­tion during the Company’s pre­vi­ously-announced conference call on February 28, 2018 at 8:30 AM ET to report fourth quarter and year-end 2018 financial results. 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 ID 4246798. 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 Selinexor

Selinexor is a first-in-class, oral Selective Inhibitor of Nuclear Export (SINE) com­pound. Selinexor functions by binding with and inhibiting the nuclear export protein XPO1 (also called CRM1), leading to the accumulation of tumor sup­pressor proteins in the cell nucleus. This reinitiates and amplifies their tumor sup­pressor function and is believed to lead to the selective induction of apop­tosis in cancer cells, while largely sparing nor­mal cells. In 2018, Karyopharm reported pos­i­tive data from the Phase 2b STORM study eval­u­ating selinexor in com­bi­na­tion with low-dose dexa­meth­a­sone in patients with triple class refractory multiple myeloma who have been pre­vi­ously exposed to all five of the most commonly prescribed anti-myeloma ther­a­pies cur­rently avail­able. Selinexor has been granted Orphan Drug Desig­na­tion in multiple myeloma and Fast Track desig­na­tion for the patient pop­u­la­tion eval­u­ated in the STORM study. Karyopharm’s New Drug Application (NDA) has been accepted for filing and granted Priority Review by the FDA, and oral selinexor is cur­rently under review by the FDA as a possible new treat­ment for patients with triple class refractory multiple myeloma. The Company has also submitted a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) with a request for con­di­tional approval and was granted accelerated assess­ment. Selinexor is also being studied in patients with re­lapsed or refractory diffuse large B-cell lym­phoma (DLBCL). In 2018, Karyopharm reported pos­i­tive top-line results from the Phase 2b SADAL study eval­u­ating selinexor in patients with re­lapsed or refractory DLBCL after at least two prior multi-agent ther­a­pies and who are in­eli­gible for trans­plan­ta­tion, in­­clud­ing high dose chemo­ther­apy with stem cell rescue. Selinexor has received Fast Track desig­na­tion from the FDA for the patient pop­u­la­tion eval­u­ated in the SADAL study. 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 an investigator-sponsored study 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.

About Karyopharm Therapeutics

Karyopharm Therapeutics Inc. (Nasdaq:KPTI) is a clin­i­cal-stage pharma­ceu­tical com­pany focused on the discovery and devel­op­ment of novel first-in-class drugs directed against nuclear transport 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). 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, which was founded by Dr. Sharon Shacham, cur­rently 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 our ex­pec­ta­tions relating to sub­missions to, and the review and poten­tial approval of selinexor by, regu­la­tory author­i­ties, in­­clud­ing the antic­i­pated timing of such sub­missions and actions, and the poten­tial avail­a­bil­ity of accelerated approval path­ways, the thera­peutic poten­tial of and poten­tial clin­i­cal devel­op­ment plans for Karyopharm's drug can­di­dates, especially selinexor, and the plans for com­mer­cial­iza­tion. 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 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 STORM study in patients with triple class refractory myeloma or the SADAL study in patients with re­lapsed or refractory DLBCL 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 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: 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; 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 Quarterly Report on Form 10-Q for the quarter ended September 30, 2018, which was filed with the Se­cu­ri­ties and Exchange Com­mis­sion (SEC) on November 8, 2018, 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.