“This has been a landmark quarter for Karyopharm as we saw the accelerated approval and commercial launch of XPOVIO, the first and only oral nuclear export inhibitor approved in the U.S., indicated for patients with heavily pretreated multiple myeloma,” said
Third Quarter 2019 Highlights and Recent Progress
XPOVIO (selinexor) in Multiple Myeloma
- XPOVIO U.S. Commercial Rollout Off to a Strong Start. Oral XPOVIO, Karyopharm’s first-in-class, nuclear export inhibitor, became commercially available to patients in the U.S on
July 9, 2019and generated net product sales of $12.8 millionin the third quarter. As of September 30, 2019, over 500 XPOVIO prescriptions have been fulfilled, driven by strong demand from both academic and community-based oncologists. In less than 3 months on the market, XPOVIO has been prescribed by more than 300 unique physicians and healthcare accounts.
Third quarter sales were driven by a combination of new patient starts, prescription refills, and initial channel inventory to Karyopharm’s distribution partners. Patient demand for XPOVIO continued to increase in each subsequent month of the quarter following its accelerated approval by the
U.S. Food and Drug Administration( FDA) in July. Rapid insurance coverage for XPOVIO has been a key contributor to its early commercial success with XPOVIO already being added to numerous national commercial and Medicareformularies and coverage policies. Based on prescription fulfillment data through the specialty pharmacy channel, Karyopharm estimates that approximately 60% of XPOVIO prescriptions have been dispensed to patients with Medicarecoverage and 35% to patients with commercial insurance, with the remaining 5% of patients having either Medicaidor another form of prescription coverage.
- XPOVIO Receives Accelerated Approval from the
FDA. On July 3, 2019, the FDAapproved XPOVIO for use in combination with dexamethasone 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. XPOVIO is the first of a novel drug class designated selective inhibitors of nuclear export (SINE) and is the first ever nuclear export inhibitor approved for human use. This first indication received accelerated approval based on response rate. As with all accelerated approvals, continued approval for the treatment of myeloma may be contingent upon verification and description of clinical benefit in a confirmatory trial. The ongoing Phase 3 BOSTON study is intended to serve as the confirmatory trial for the accelerated approval of XPOVIO.
- XPOVIO Phase 2b STORM Study Results Published in the
New England Journal of Medicine. Results from Karyopharm’s Phase 2b STORM study evaluating XPOVIO in patients with heavily pretreated, triple class refractory multiple myeloma were published in the New England Journal of Medicineon August 22, 2019. In STORM, XPOVIO achieved a 26% overall response rate, median overall survival (OS) of 8.6 months, and a median survival of 15.6 months in the 39% of patients with a minimal response or better.
- XPOVIO Granted Seven Years Orphan Drug Market Exclusivity by
FDA. In September 2019, Karyopharm received confirmation from the FDAthat the Company is entitled to seven years of orphan-drug exclusivity for XPOVIO’s approved indication for the treatment of patients with relapsed or refractory multiple myeloma, pursuant to section 527 of the Federal Food, Drug, and Cosmetic Act.
- Five Abstracts Presented at the 17th
International Myeloma Workshop(IMW). Multiple data presentations at this year’s IMW, held September 12-15, 2019, continue to reinforce the potential clinical utility of XPOVIO as a new therapeutic option for patients with relapsed or refractory multiple myeloma. One key abstract, in particular, titled, “Outcomes of Triple Class Refractory Penta-Exposed Multiple Myeloma (MM),” ( Cornell, et al) compared the OS rate from the retrospective MAMMOTH study (Gandhi, 2019), which evaluated outcomes from patients with relapsed or refractory multiple myeloma after their disease became refractory to CD38 monoclonal antibodies, with a similarly-matched cohort of patients from Karyopharm’s Phase 2b STORM study. Patients in STORM, who received selinexor and dexamethasone as first line of therapy after their disease became triple class refractory (n=64), compared to matched patients receiving currently available therapies from the MAMMOTH cohort (n=128), showed an unadjusted hazard ratio (HR) of 0.64 (p=0.043). An adjusted analysis, which takes into consideration differences in baseline characteristics between the two groups, showed a HR of 0.55 (p=0.009).
- Decision from
European Medicines Agency(EMA) for Marketing Authorization Application (MAA) Expected in Early 2020. In January 2019, Karyopharm submitted an MAA to the EMA requesting conditional approval for selinexor, in combination with dexamethasone, as a new treatment for patients with heavily pretreated multiple myeloma based on the results of the Phase 2b STORM study. The Company expects to receive a decision on the MAA in early 2020.
- Pivotal Phase 3 BOSTON Study On Track. Karyopharm’s pivotal, randomized Phase 3 BOSTON study is progressing and patient enrollment was completed in January 2019. Top-line data are expected in early 2020 contingent upon the occurrence of progression-free survival (PFS) events, the primary endpoint of the study. The
BOSTONstudy is evaluating 100mg of selinexor dosed once weekly in combination with the proteasome inhibitor Velcade® (bortezomib) (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, are expected to be used to support regulatory submissions to the FDAand EMA requesting the use of selinexor in combination with Velcade and dexamethasone in patients with multiple myeloma who have received at least one prior therapy.
Selinexor in Diffuse Large B-Cell Lymphoma (DLBCL)
- NDA Expected to be Submitted by End of 2019. Following the positive results from the Phase 2b SADAL study that were first presented at the
America Society of Hematology2018 Annual Meeting and then updated in June at the 2019 International Conference on Malignant Lymphoma, Karyopharm expects to submit a New Drug Application (NDA) to the FDAby the end of 2019 requesting accelerated approval for selinexor as a treatment for patients with relapsed or refractory DLBCL after at least two prior multi-agent therapies and who are ineligible for stem cell transplantation including CAR-T (chimeric antigen receptor modified T cell) therapy. The Company also expects to submit an MAA to the EMA in 2020 requesting conditional approval for selinexor in the same indication. In addition to orphan drug designation, selinexor was granted fast track designation for this indication by the FDAin 2018.
Selinexor in Solid Tumors
- Ongoing Phase 3 Portion of the Phase 2/3 SEAL Study in Liposarcoma. Karyopharm previously reported positive results from the Phase 2 portion of the randomized, blinded Phase 2/3 SEAL study evaluating single-agent selinexor versus placebo in patients with previously treated, advanced unresectable dedifferentiated liposarcoma. Enrollment is currently ongoing in the Phase 3 portion of the SEAL study. Top-line data from the Phase 3 portion of the SEAL study are anticipated in 2020. Assuming a positive outcome on the primary endpoint of PFS, the Company intends to use the data from the SEAL study to support NDA and MAA submissions requesting approval for selinexor for patients with advanced unresectable dedifferentiated liposarcoma.
Corporate and Financial Updates
- Executed Royalty Agreement with
HealthCare Royalty Partnersfor up to $150 Million. In September 2019, Karyopharm executed a royalty agreement with HealthCare Royalty Partners(HCR) for up to $150 millionto support the ongoing development and commercialization of XPOVIO. Under the terms of the agreement, Karyopharm received $75 millionin September 2019and is eligible to receive an additional $75 millionupon the achievement of future regulatory and commercial milestones, as well as closing conditions. In exchange for the first $75 million, HCR will receive a tiered royalty in the mid-single digits based on worldwide net revenues of XPOVIO and any other future products beginning in October 2019.
Third Quarter 2019 Financial Results
Net product revenue for the quarter ended
License and other revenue for the third quarter 2019 was
Cost of sales for the third quarter 2019, was
Research and development expense for the third quarter 2019 was
Karyopharm reported a net loss of
Cash, cash equivalents, restricted cash and investments as of
2019 Financial Outlook
Based on its current operating plans, Karyopharm expects its non-GAAP operating expenses, which excludes stock-based compensation expense, for the full year 2019 to be in the range of
The Company expects that its existing cash, cash equivalents and investments, and the revenue it expects to generate from XPOVIO product sales, will be sufficient to fund its planned operations into the middle of 2021.
Additional key activities expected in the remainder of 2019 include supporting the ongoing multiple myeloma regulatory filing for selinexor in
Non-GAAP Financial Information
Karyopharm uses a non-GAAP financial measure, non-GAAP operating expense, to provide operating expense guidance. Karyopharm believes this non-GAAP financial measure is useful to investors because it provides greater transparency regarding Karyopharm’s operating performance as it excludes non-cash stock compensation expense. This non-GAAP financial measure should not be considered a substitute or an alternative to GAAP total operating expense and should not be considered a measure of Karyopharm’s liquidity. Instead, non-GAAP operating expense should only be used to supplement an understanding of Karyopharm’s operating results as reported under GAAP.
Conference Call Information
Karyopharm will host a conference call today,
Important Safety Information
The most common adverse reactions observed in patients treated with XPOVIO (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%.
The full Prescribing Information for XPOVIO is available at www.XPOVIO.com.
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, commercialization of XPOVIO or any of its drug candidates, 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, 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 accelerated or conditional approval in the U.S. or EU, respectively, based on 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 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
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|Karyopharm Therapeutics Inc.
CONDENSED CONSOLIDATED BALANCE SHEETS
(in thousands, except share and per share amounts)
|Cash and cash equivalents||$||168,004||$||118,021|
|Prepaid expenses and other current assets||5,310||6,413|
|Total current assets||280,867||334,612|
|Property and equipment, net||3,240||3,863|
|Operating lease right-of-use assets||10,904||—|
|Liabilities and stockholders’ equity|
|Operating lease liabilities||1,583||—|
|Other current liabilities||1,077||327|
|Total current liabilities||39,202||46,904|
|Convertible senior notes||107,962||102,664|
|Deferred royalty obligation||73,589||—|
|Operating lease liabilities, net of current portion||13,643||—|
|Deferred revenue, net of current portion||3,479||4,532|
|Deferred rent, net of current portion||3,922|
|Preferred stock, $0.0001 par value; 5,000,000 shares authorized; none issued and outstanding||—|
|Common stock, $0.0001 par value; 200,000,000 shares authorized; 62,705,481 shares issued and
outstanding at September 30, 2019; 100,000,000 shares authorized; 60,829,308 shares issued and
outstanding at December 31, 2018
|Additional paid-in capital||884,585||857,156|
|Accumulated other comprehensive loss||(30||)||(244||)|
|Total stockholders’ equity||59,870||183,170|
|Total liabilities and stockholders’ equity||$||297,745||$||341,192|
|Karyopharm Therapeutics Inc.
CONDENSED CONSOLIDATED STATEMENTS OF OPERATIONS
(in thousands, except share and per share amounts)
|Three Months Ended,
|Nine Months Ended
|Product revenue, net||$||12,821||$||—||$||12,821||$||—|
|License and other revenue||328||239||9,976||30,130|
|Cost of sales||1,013||—||1,013||—|
|Research and development||26,270||36,427||90,761||122,482|
|Selling, general and administrative||25,267||12,966||77,032||30,076|
|Total operating expenses||52,550||49,393||168,806||152,558|
|Loss from operations||(39,401||)||(49,154||)||(146,009||)||(122,428||)|
|Other income (expense):|
|Other income (expense)||10||(13||)||(36||)||(20||)|
|Total other (expense) income, net||(1,946||)||1,085||(4,896||)||2,240|
|Loss before income taxes||(41,347||)||(48,069||)||(150,905||)||(120,188||)|
|Income tax provision||(20||)||(14||)||(38||)||(9||)|
|Net loss per share—basic and diluted||$||(0.67||)||$||(0.79||)||$||(2.46||)||$||(2.17||)|
|Weighted-average number of common shares outstanding used in net loss per share—basic and diluted||62,092,841||60,586,511||61,297,249||55,465,261|
Source: Karyopharm Therapeutics Inc.