“Earlier this week, the
Fourth Quarter 2018 and Recent Events
Selinexor in Multiple Myeloma
- FDA Advisory Committee Recommends that the FDA Should Wait for Results from the Ongoing Phase 3 BOSTON Study Before Making an Approval Decision. On
February 26, 2019, the Oncologic Drugs Advisory Committee(ODAC) of the FDAmet to review data supporting Karyopharm’s NDA requesting accelerated approval for selinexor. The proposed indication discussed was 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, one immunomodulatory agent, and one anti-CD38 monoclonal antibody. The FDA specifically asked the ODAC to vote on whether the committee believed the approval of selinexor should be delayed until the results from the ongoing, randomized Phase 3 BOSTON study, are available. In a vote of 8 Yes and 5 No, the ODAC recommended that the approval decision for selinexor should be delayed until the results of the BOSTONstudy are available. Karyopharm’s NDA is under Priority Review by the FDAwith an action date of April 6, 2019, under the PDUFA.
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 Accepts Selinexor New Drug Application and Grants Priority Review. On
October 5, 2018, the FDAaccepted for filing with Priority Review Karyopharm’s NDA seeking accelerated approval for selinexor, its first-in-class, oral SINE compound, as a new treatment for patients with triple class refractory multiple myeloma. The FDAalso assigned a PDUFA action date of April 6, 2019.
- Submitted Marketing Authorization Application (MAA) to the
European Medicines Agency(EMA). A MAA was submitted to the EMA on January 8, 2019for selinexor requesting conditional approval for the treatment of patients with relapsed or refractory multiple myeloma who have received at least three prior lines of therapy and whose disease is refractory to at least one proteasome inhibitor, one immunomodulatory agent, and one anti-CD38 monoclonal antibody. Karyopharm also announced that the selinexor MAA has been granted accelerated assessment by the EMA’s Committee for Medicinal Products for Human Use.
- Updated Phase 2b STORM Data Presented at
American Society of Hematology2018 Annual Meeting (ASH 2018). Additional results from Part 2 of the Phase 2b STORM study were highlighted in an oral presentation at ASH 2018. For the STORM study’s primary objective, the overall response rate (ORR) was 26.2%, which included two stringent complete responses (sCRs), six very good partial responses (VGPRs) and 24 partial responses (PRs) in patients with triple class refractory myeloma who have been previously exposed to all five of the most commonly prescribed anti-myeloma therapies currently available. The two sCRs were negative for minimal residual disease, one at the level of 1x10-6 and one at 1x10-4; this is particularly significant in this highly refractory population. The Disease Control Rate for patients who had achieved stable disease or better was 78.7%. All responses were confirmed by an Independent Review Committee. Median progression-free survival (PFS) was 3.7 months and the median duration of response (DOR) was 4.4 months. Median overall survival (OS) across the study was 8.6 months. Median OS in the approximately 40% of patients with at least a minimal response (MR) on selinexor and dexamethasone was 15.6 months compared to a median OS of 1.7 months in patients whose disease progressed or was not evaluable (p<0.0001). The short median OS of patients with no response to selinexor is consistent with the lack of available effective therapies for the very heavily pretreated population who entered the study. The most common adverse events (AEs) included thrombocytopenia, nausea/vomiting, fatigue and decreased appetite. Each patient on STORM experienced at least one AE. AEs were generally predictable and manageable with dose adjustments and/or supportive care, 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 the STORM study (Vogl et al., J Clin Oncol, 2018) and from other selinexor studies.
- Updated Phase 1b/2 STOMP Data Presented at ASH 2018. Two abstracts featuring clinical data from two treatment arms of the ongoing Phase 1b/2 STOMP study in patients with relapsed or refractory multiple myeloma were selected for oral and poster presentations at ASH 2018. The oral presentation highlighted updated data from the arm evaluating selinexor in combination with Darzalex® (daratumumab) and low-dose dexamethasone (SDd). In this arm, the combination demonstrated an ORR of 79% in patients with heavily pretreated, Darzalex®-naïve multiple myeloma and an ORR of 73% in the overall study population. The poster presentation described updated data from the arm evaluating selinexor in combination with Pomalyst® (pomalidomide) and low-dose dexamethasone (SPd). In this arm, the combination demonstrated an ORR of 54% in patients with Pomalyst®-naïve and Revlimid®-relapsed or -refractory multiple myeloma, with PFS of 12.2 months. The combination demonstrated an ORR of 50% in the overall study population. Among the patients evaluated for safety as of the data cutoff date, the most common treatment-related AEs were cytopenias, along with gastrointestinal and constitutional symptoms; most manageable with dose modifications and/or standard supportive care.
- Pivotal Phase 3 BOSTON Study in
Progress. Karyopharm’s pivotal, randomized Phase 3 BOSTON study is progressing and in January 2019, the Company announced the completion of enrollment in the study. Top-line data is expected at the earliest by the end of 2019 or into 2020 contingent upon the occurrence of PFS events, the primary endpoint in the study. The BOSTONstudy is evaluating 100mg of selinexor dosed once weekly in combination with the proteasome inhibitor Velcade® (once weekly) and low dose dexamethasone (SVd), compared to standard twice weekly Velcade and low dose dexamethasone (Vd) in patients with multiple myeloma who have had one to three prior lines of therapy. Data from the BOSTONstudy, if positive, would be used to support regulatory submissions to the FDAand EMA requesting the use of selinexor in second line multiple myeloma, and confirming the Company’s requests for accelerated and conditional approvals, respectively, using data from the Phase 2b STORM study.
Selinexor in Diffuse Large B-Cell Lymphoma (DLBCL)
- Received Fast Track Designation from
FDAfor the Treatment of Patients with Relapsed or Refractory DLBCL. In addition to Orphan Drug Designation, selinexor was recently granted Fast Track designation by the FDAfor the treatment of patients with diffuse large B-cell lymphoma (DLBCL) who have received at least two prior therapies and are not eligible for high dose chemotherapy with stem cell rescue or CAR-T therapy.
- Top-Line Phase 2b SADAL Data in DLBCL Presented at ASH 2018. Top-line results from the fully enrolled Phase 2b SADAL study was presented at ASH 2018. The SADAL study is designed to evaluate single agent oral selinexor 60mg for patients with relapsed or refractory DLBCL who are not eligible for stem cell transplantation. Based on the modified intention-to-treat analysis from the first 115 of 127 patients, as adjudicated by an independent central radiological committee, selinexor achieved an ORR of 29.6%. The median DOR across responding patients was 9.2 months. Patients with a complete response (CR) had a median DOR of 23.0 months and patients with a PR had a median DOR of 7.8 months. The median OS was 9.1 months for all patients in the study. As of the data cutoff date, median survival for the patients with a CR or PR was 29.7 months. The median survival for patients with best response of progressive disease or who were not evaluable for response was 3.2 months. Among the patients evaluated for safety as of the data cutoff date, the most common treatment-related AEs were gastrointestinal and constitutional symptoms, along with cytopenias; most AEs were manageable with dose modifications and/or supportive care. Based on the results from the Phase 2b SADAL study, Karyopharm plans to submit an NDA to the
FDAwith a request for accelerated approval for oral selinexor in this relapsed or refractory DLBCL patient population and the Company is working closely with the FDAto determine the appropriate timeline. Karyopharm is also planning to submit a MAA to the EMA with a request for conditional approval in the same indication.
Selinexor in Solid Tumors
- Ongoing Phase 3 Portion of the Phase 2/3 SEAL Study in Liposarcoma. Karyopharm previously reported results from the successful Phase 2 portion of the blinded, randomized Phase 2/3 SEAL study evaluating single-agent selinexor versus placebo in patients with previously treated, advanced unresectable dedifferentiated liposarcoma. Enrollment and dosing are currently ongoing in the Phase 3 portion of the SEAL study and, assuming a positive outcome on the primary end point of PFS, the Company intends to use the data from the SEAL study to support a NDA and a MAA submission requesting approval for oral selinexor for patients with advanced unresectable dedifferentiated liposarcoma. Top-line data from the Phase 3 portion of the SEAL study are anticipated in 2020.
- Ongoing Investigator Sponsored Phase 2/3 Trial as Maintenance Therapy in Endometrial Cancer. A randomized Phase 2/3 study of selinexor versus placebo as maintenance therapy in patients with one or two prior platinum-based treatments for advanced endometrial cancer, led by Dr.
Ignace Vergote, Head of the Department of Obstetrics and Gynaecologyand Gynaecologic Oncology at the Catholic University of Leuven, Belgium, is currently ongoing. Top-line data from this study are anticipated in 2020.
- Michael P. Mason Appointed Chief Financial Officer. Karyopharm announced the appointment of
Michael P. Masonas Chief Financial Officer. Mr. Mason formerly served as Vice President of Finance and Treasurer at Alnylam Pharmaceuticals, Inc., a public biopharmaceutical company. He brings over 18 years of diversified financial experience to Karyopharm and has deep expertise in global financial operations and controls, financing transactions, business planning and supporting pharmaceutical product launches.
Full Year and Fourth Quarter 2018 Financial Results
Cash, cash equivalents and investments as of
License and other revenue for the year ended
For the year ended
Karyopharm reported a net loss of
For the quarter ended
Karyopharm reported a net loss of
Based on its current operating plans, Karyopharm expects that its existing cash, cash equivalents and investments will be sufficient to fund its operations into the second half of 2020, which currently assumes the commercial launch of selinexor in the U.S. in the second quarter of 2019. If the
Further Information About Potential Accelerated Approval for Selinexor in Multiple Myeloma
Conference Call Information
Karyopharm will host a conference call today,
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
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Pomalyst® are registered trademarks of
Darzalex® is a registered trademark of
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Karyopharm Therapeutics Inc.
Consolidated Balance Sheets
(in thousands, except share and per share amounts)
|Cash and cash equivalents||$||118,021||$||68,997|
|Prepaid expenses and other current assets||6,413||1,754|
|Total current assets||334,612||148,423|
|Property and equipment, net||3,863||2,185|
|LIABILITIES AND STOCKHOLDERS’ EQUITY|
|Other current liabilities||327||133|
|Total current liabilities||46,904||49,467|
|Convertible senior notes||102,664||—|
|Deferred revenue, net of current portion||4,532||—|
|Deferred rent, net of current portion||3,922||1,363|
|Commitments and contingencies (Note 8)|
|Preferred stock, $0.0001 par value; 5,000,000 shares authorized; none issued and outstanding||—||—|
|Common stock, $0.0001 par value; 100,000,000 shares authorized; 60,829,308 and 49,533,150
shares issued and outstanding at December 31, 2018 and 2017, respectively
|Additional paid-in capital||857,156||625,017|
|Accumulated other comprehensive loss||(244||)||(217||)|
|Total stockholders’ equity||183,170||129,464|
|Total liabilities and stockholders’ equity||$||341,192||$||180,294|
Karyopharm Therapeutics Inc.
Consolidated Statements of Operations
(in thousands, except share and per share amounts)
For the Quarter Ended,
|For the Year Ended
|License and other revenue||$||206||$||1,534||$||30,336||$||1,605|
|Research and development||38,890||34,833||161,372||107,273|
|General and administrative||18,771||6,153||48,847||24,870|
|Total operating expenses||57,661||40,986||210,219||132,143|
|Loss from operations||(57,455||)||(39,452||)||(179,883||)||(130,538||)|
|Other income (expense):|
|Total other (expense) income, net||(738||)||421||1,502||1,617|
|Loss before income taxes||(58,193||)||(39,031||)||(178,381||)||(128,921||)|
|Provision for income taxes||(17||)||(9||)||(26||)||(63||)|
|Net loss per share—basic and diluted||$||(0.96||)||$||(0.80||)||$||(3.14||)||$||(2.81||)|
|Weighted-average number of common shares outstanding used
in net loss per share—basic and diluted
Source: Karyopharm Therapeutics Inc.