• Application Seeks Accelerated Approval for Selinexor as a Treatment for Patients with Penta-Refractory Multiple Myeloma
• PDUFA Date Set for April 6, 2019

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) has accepted for filing with Priority Review its New Drug Application (NDA) seeking accelerated approval for selinexor, its first in class, oral SINE com­­pound, as a new treat­ment for patients with penta-refractory multiple myeloma. The FDA also granted Karyopharm’s request for Priority Review and assigned an action date of April 6, 2019 under the Prescription Drug User-Fee Act (PDUFA). In its acceptance letter, the FDA has stated that it is cur­rently planning to hold an advisory committee meeting to discuss this appli­ca­tion.

“As a poten­tial new ther­apy with a novel mech­a­nism and compelling clin­i­cal profile, we believe oral selinexor, if approved, will provide a meaningful thera­peutic option for patients battling highly resistant, penta-refractory myeloma,” said Sharon Shacham, PhD, MBA, Founder, Pres­i­dent and Chief Scientific Officer of Karyopharm. “The acceptance of this NDA for review and grant of Priority Review mark sig­nif­i­cant mile­stones for the selinexor pro­gram, and further underscores the high level of unmet need in this patient pop­u­la­tion. We look for­ward to work­ing with the FDA during the review process.”

Provided mar­ket­ing approval is granted by the FDA, Karyopharm plans to com­mer­cial­ize selinexor in the U.S. as early as the first half of 2019. The Company also plans to submit a Marketing Authori­za­tion Application to the European Medicines Agency in early 2019 with a request for con­di­tional approval.

Priority Review is granted by the FDA to drugs that, if approved, would provide sig­nif­i­cant im­prove­ments in the safety or effectiveness of the treat­ment, diag­nosis, or prevention of a serious con­di­tion when com­pared to standard appli­ca­tions. Selinexor has received both Orphan Drug and Fast Track desig­na­tions from the FDA for the treat­ment for patients with penta-refractory multiple myeloma.

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. To date, over 2,600 patients have been treated with selinexor. In April and September 2018, Karyopharm reported pos­i­tive top-line data from the Phase 2b STORM study eval­u­ating selinexor in com­bi­na­tion with low-dose dexa­meth­a­sone in patients with penta-refractory multiple myeloma. 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 penta-refractory multiple myeloma. The Company also plans to submit a Marketing Authori­za­tion Application (MAA) to the European Medicines Agency (EMA) in early 2019 with a request for con­di­tional approval. 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 diffuse large B-cell lym­phoma (SADAL), 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.

Further Information About Potential Accelerated Approval for Selinexor in Multiple Myeloma

The FDA instituted its Accelerated Approval Program to allow for expedited approval of drugs that treat serious con­di­tions and that fill an unmet medical need based on a surrogate end­point or an intermediate clin­i­cal end­point thought to predict clin­i­cal benefit, like over­all response rate (ORR). Accelerated approval is avail­able only for drugs that provide a meaningful thera­peutic benefit over existing treat­ments at the time of con­sid­er­a­tion of the appli­ca­tion for accelerated approval, which the FDA has reiterated in its feedback to the Company. Particularly in disease areas with multiple avail­able and poten­tial new ther­a­pies, such as multiple myeloma, accelerated approval carries a high regu­la­tory threshold. Consistent with its general guidance, the FDA has noted to the Company its pref­er­ence for ran­dom­ized studies geared to­ward full approval, which the Company has under­taken with the ongoing pivotal, Phase 3 BOSTON study, and has reminded the Company that accelerated approval requires patients to have exhausted all avail­able approved ther­a­pies. FDA’s Fast Track desig­na­tion is avail­able to thera­peutics treating an unmet medical need in a serious con­di­tion; the Company has received Fast Track desig­na­tion from the FDA specifically for the pop­u­la­tion treated in the STORM trial. In light of this recognition that the STORM patient pop­u­la­tion rep­re­sents an unmet medical need and the pos­i­tive top-line data reported in April and September 2018, the Company believes that the STORM study should sup­port its request to the FDA for accelerated approval.

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 and to 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 penta-refractory myeloma 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 June 30, 2018, which was filed with the Se­cu­ri­ties and Exchange Com­mis­sion (SEC) on August 7, 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.
Revlimid® and Pomalyst® are registered trademarks of Celgene Corpo­ra­tion
Kyprolis® is a registered trademark of Onyx Pharma­ceu­ticals, Inc.
Darzalex® is a registered trademark of Janssen Biotech, Inc.

Source: Karyopharm.