On February 8, 2022 Karyopharm Therapeutics Inc. (Nasdaq: KPTI) ("Karyopharm," the "Company," "we" and "our"), a commercial-stage pharmaceutical company pioneering novel cancer therapies, reported financial results for the fourth quarter and full year ended December 31, 2021 (Press release, Karyopharm, FEB 8, 2022, View Source [SID1234607819]). In addition, Karyopharm highlighted select corporate milestones, including details regarding the ongoing U.S. commercialization of XPOVIO (selinexor) and provided an overview of its key clinical development programs.
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"I am exceptionally proud of the Karyopharm team’s performance in 2021 as we advanced all aspects of our business, including securing a commercialization partnership with Menarini for Europe and other key global territories," said Richard Paulson, President and Chief Executive Officer of Karyopharm. "We delivered consecutive quarters of double-digit growth driven by XPOVIO’s strong commercial performance in the second half of the year and head into 2022 with momentum as we continue to prioritize driving sales and the adoption of XPOVIO in multiple myeloma. Our momentum is accelerating as we reported positive top-line data from the SIENDO study evaluating selinexor as a maintenance therapy following front-line chemotherapy in patients with advanced or recurrent endometrial cancer. Based on these findings, Karyopharm intends to submit a supplemental New Drug Application to the U.S. Food and Drug Administration in the first half of this year. We are also progressing our pipeline in key indications of multiple myeloma, myelodysplastic syndromes and myelofibrosis to improve survival and outcomes for patients with cancer."
Fourth Quarter 2021 and Recent Highlights
XPOVIO Commercial Performance
Achieved U.S. net product revenue for the year ended December 31, 2021 of $98.4 million, up 29% compared to same prior year period. Net product revenue for the fourth quarter of 2021 was $29.8 million, up 47% compared to same prior year period, representing sequential growth of 12% compared to the third quarter of 2021.
Increased uptake in second line to fourth line multiple myeloma treatment settings; fastest growing multiple myeloma therapy used in third line regimens.
Continued positive shift in intent to prescribe metrics through growing confidence with community physicians.
R&D Highlights for Selinexor and Eltanexor
The SIENDO study (n=263) met its primary endpoint of a statistically significant improvement in median progression-free survival (PFS) compared to placebo. Selinexor-treated patients had a median PFS of 5.7 months compared to 3.8 months for patients on placebo with a hazard ratio (HR) of 0.70 (p=0.0486). Other key preliminary findings include:
Selinexor demonstrated a sustained and long-term benefit as seen at 12 months with a 37% increase in probability that selinexor-treated patients will be in remission compared to placebo.
Selinexor was well tolerated with no new safety signals identified, and a low discontinuation rate of 10.5% due to adverse events.
Patients with wild-type p53 (current n=103), a pre-specified subgroup, achieved a statistically significant improvement in median PFS with a HR of 0.38 (p=0.0006).
Company plans to submit a supplemental New Drug Application to the U.S. Food and Drug Administration (FDA), and submit detailed results for presentation at medical meetings, both in the first half of 2022.
The U.S. FDA granted orphan drug designation for eltanexor for the treatment of myelodysplastic syndromes (MDS).
European Medicines Agency validated the Marketing Authorization Application (MAA) for NEXPOVIO (selinexor) in combination with Velcade (bortezomib) and low-dose dexamethasone for the treatment of multiple myeloma following at least one prior therapy. The MAA will be reviewed by the Committee for Medicinal Products for Human Use, which is expected to issue an opinion to the European Commission in the first half of 2022.
Commenced dosing in the Phase 2 expansion of an ongoing Phase 1/2 study evaluating eltanexor, Karyopharm’s novel oral selective inhibitor of nuclear export (SINE) compound, in patients with intermediate or high-risk hypomethylating agents refractory MDS (KPT-8602-801; NCT02649790).
Commenced dosing in a new Phase 2 study evaluating oral selinexor as a monotherapy versus physician’s choice in patients with myelofibrosis (MF) previously treated with a JAK 1/2 inhibitor (XPORT-MF-035; NCT04562870).
Presented updated data from the Phase 2 ESSENTIAL study, an investigator-sponsored study evaluating selinexor in patients with MF previously treated with JAK inhibition, at the American Society of Hematology (ASH) (Free ASH Whitepaper) 2021 Annual Meeting and Exposition.
Karyopharm’s partner, Antengene, obtained conditional approval for marketing by the China National Medical Products Administration for XPOVIO in combination with dexamethasone in patients with relapsed or refractory multiple myeloma who have received prior therapies and whose disease is refractory to at least a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody.
Karyopharm partner Promedico Ltd., a member of the Neopharm Group, received a principal approval letter of their indication extension application from the Israeli Ministry of Health granting the approval of XPOVIO in combination with bortezomib and dexamethasone for the treatment of adult patients with multiple myeloma who have received at least one prior therapy.
The National Comprehensive Cancer Network (NCCN) added a selinexor combination regimen with Kyprolis (carfilzomib) and dexamethasone to its Clinical Procedure Guidelines in Oncology for Previously Treated Myeloma.
Corporate and Business Highlights
Entered into an exclusive license agreement with the Menarini Group, ("Menarini"), whereby Menarini will commercialize NEXPOVIO (selinexor) in Europe and other key global territories. In exchange, Karyopharm received an upfront payment of $75.0 million and is eligible to receive up to an additional $202.5 million in future milestones, plus tiered double-digit royalties on net sales of NEXPOVIO in the licensed territories. In addition, Karyopharm will receive up to $15.0 million in each calendar year from 2022 to 2025 in reimbursement for certain research and development expenses.
Sohanya Cheng promoted to Chief Commercial Officer and Peter K Honig, MD, MPH, appointed to the Board of Directors.
Full Year and Fourth Quarter 2021 Financial Results
Net product revenue: Net product revenue for the fourth quarter of 2021 was $29.8 million, up 47% as compared to $20.2 million for the fourth quarter of 2020. Net product revenue for the year ended December 31, 2021, was $98.4 million, up 29% compared to $76.2 million for the year ended December 31, 2020.
License and other revenue: License and other revenue for the fourth quarter of 2021 was $96.5 million, compared to $14.9 million for the fourth quarter of 2020. This increase was driven by $75.0 million of revenue recognized related to the upfront payment that Karyopharm received from Menarini in connection with the license agreement entered into during the fourth quarter of 2021. In addition, Karyopharm recognized $19.5 million for a milestone payment related to commercial launch within the Antengene Therapeutics Limited territory following regulatory approval received for selinexor for the treatment of patients with multiple myeloma and diffuse large B-cell lymphoma. License and other revenue for the year ended December 31, 2021 was $111.4 million, compared to $31.9 million for the year ended December 31, 2020.
Cost of sales: Cost of sales for the fourth quarter of 2021 was $0.7 million, compared to $1.1 million for the fourth quarter of 2020. Cost of sales for the year ended December 31, 2021 was $3.4 million, compared to $2.7 million for the year ended December 31, 2020. Cost of sales reflects the costs of XPOVIO units sold and third-party royalties on net product revenue.
Research and development (R&D) expenses: R&D expenses for the fourth quarter of 2021 were $44.0 million, compared to $37.2 million for the fourth quarter of 2020. R&D expenses for the year ended December 31, 2021 were $160.8 million, compared to $150.8 million for the year ended December 31, 2020. The increase in R&D expenses in 2021 compared to 2020 was primarily attributable to $7.4 million related to the acquisition of certain assets from Neumedicines Inc., which closed in the third quarter of 2021, coupled with costs for key clinical trials in 2021, including costs incurred in preparation for a Phase 3 study evaluating selinexor in combination with pomalidomide in patients with relapsed or refractory multiple myeloma.
Selling, general and administrative (SG&A) expenses: SG&A expenses for the fourth quarter of 2021 were $34.6 million, compared to $33.9 million for the fourth quarter of 2020. SG&A expenses for the year ended December 31, 2021, were $143.8 million, compared to $126.4 million for the year ended December 31, 2020. The increase in SG&A expenses compared to the prior year was due primarily to increased personnel costs.
Interest expense: Interest expense for the fourth quarter of 2021 was $7.9 million, compared to $7.1 million for the fourth quarter of 2020. Interest expense for the year ended December 31, 2021 was $26.0 million, compared to $27.1 million for the year ended December 31, 2020. The decrease in interest expense year over year was primarily attributable to a $7.3 million decrease in non-cash interest expense related to Karyopharm’s 3.00% senior convertible notes due 2025, as a result of the January 1, 2021 adoption of ASU No. 2020-06, Debt—Debt with Conversion and Other Options and Derivatives and Hedging—Contracts in Entity’s Own Equity, partially offset by a $6.2 million increase in interest expense related to the deferred royalty obligation following Karyopharm’s June 2021 amendment of its Revenue Interest Agreement with HealthCare Royalty Management, LLC.
Net income (loss): Karyopharm reported net income of $38.7 million, or $0.51 per basic share and $0.46 per diluted share, for the fourth quarter of 2021, compared to a net loss of $43.4 million, or $0.59 per basic and diluted share, for the fourth quarter of 2020. Net income (loss) includes non-cash stock-based compensation expense of $6.9 million and $6.3 million for the fourth quarters of 2021 and 2020, respectively. Karyopharm reported a net loss of $124.1 million, or $1.65 per basic and diluted share, for the year ended December 31, 2021, compared to a net loss of $196.3 million, or $2.72 per basic and diluted share, for the year ended December 31, 2020. Net loss includes non-cash stock-based compensation expense of $29.8 million and $24.4 million for the years ended December 31, 2021 and 2020, respectively.
Cash position: Cash, cash equivalents, restricted cash and investments as of December 31, 2021 totaled $235.6 million, compared to $276.7 million as of December 31, 2020.
2022 Financial Outlook
Based on its current operating plans, Karyopharm expects the following for full year 2022:
XPOVIO net product revenue to be in the range of $135 million to $145 million.
Non-GAAP R&D and SG&A expenses, excluding stock-based compensation expense, for the year ending December 31, 2022, to be in the range of $265 million to $280 million. Karyopharm has not reconciled the full year 2022 outlook for non-GAAP R&D and SG&A expenses to full year 2022 outlook for GAAP R&D and SG&A expenses because Karyopharm cannot reliably predict without unreasonable efforts the timing or amount of the factors that substantially contribute to the projection of stock compensation expense, which is excluded from the full year 2022 outlook for non-GAAP R&D and SG&A expenses.
The Company expects that its existing cash, cash equivalents and investments, and the revenue it expects to generate from XPOVIO product sales, as well as revenue generated from its license agreements, will be sufficient to fund its planned operations into early 2024.
Non-GAAP Financial Information
Karyopharm uses a non-GAAP financial measure, including non-GAAP R&D and SG&A expenses, to provide operating expense guidance. Non-GAAP R&D and SG&A expenses exclude stock-based compensation expense. 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 R&D and SG&A expenses and should not be considered a measure of Karyopharm’s liquidity. Instead, non-GAAP R&D and SG&A expenses 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, February 8, 2022, at 8:30 a.m. Eastern Time, to discuss the fourth quarter and full year 2021 financial results and financial outlook for 2022 and to provide other business highlights. To access the conference call, please dial (888) 349-0102 (local) or (412) 902-4299 (international) at least 10 minutes prior to the start time and ask to be joined into the Karyopharm Therapeutics call. A live audio webcast of the call, along with accompanying slides, will be available under "Events & Presentations" in the Investor section of the Company’s website, View Source An archived webcast will be available on the Company’s website approximately two hours after the event.
About XPOVIO (selinexor)
XPOVIO is a first-in-class, oral exportin 1 (XPO1) inhibitor and the first of Karyopharm’s Selective Inhibitor of Nuclear Export (SINE) compounds to be approved for the treatment of cancer. XPOVIO functions by selectively binding to and inhibiting the nuclear export protein XPO1. XPOVIO is approved in the U.S. and marketed by Karyopharm in multiple oncology indications, including: (i) in combination with Velcade (bortezomib) and dexamethasone (XVd) in patients with multiple myeloma after at least one prior therapy; (ii) in combination with dexamethasone in patients with heavily pre-treated multiple myeloma; and (iii) in patients with diffuse large B-cell lymphoma (DLBCL), including DLBCL arising from follicular lymphoma, after at least two lines of systemic therapy. XPOVIO (also known as NEXPOVIO in certain countries) has received regulatory approvals in a growing number of ex-U.S. territories and countries, including Europe, the United Kingdom, China, South Korea and Israel, and is marketed in those areas by Karyopharm’s global partners. Selinexor is also being investigated in several other mid- and late-stage clinical trials across multiple high unmet need cancer indications, including in endometrial cancer and myelofibrosis.
For more information about Karyopharm’s products or clinical trials, please contact the Medical Information department at:
Tel: +1 (888) 209-9326
Email: [email protected]
XPOVIO (selinexor) is a prescription medicine approved:
In combination with bortezomib and dexamethasone for the treatment of adult patients with multiple myeloma who have received at least one prior therapy (XVd).
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 (Xd).
For the treatment of adult patients with relapsed or refractory diffuse large B–cell lymphoma (DLBCL), not otherwise specified, including DLBCL arising from follicular lymphoma, after at least two lines of systemic therapy. 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 confirmatory trial(s).
SELECT IMPORTANT SAFETY INFORMATION
Warnings and Precautions
Thrombocytopenia: Monitor platelet counts throughout treatment. Manage with dose interruption and/or reduction and supportive care.
Neutropenia: Monitor neutrophil counts throughout treatment. Manage with dose interruption and/or reduction and granulocyte colony–stimulating factors.
Gastrointestinal Toxicity: Nausea, vomiting, diarrhea, anorexia, and weight loss may occur. Provide antiemetic prophylaxis. Manage with dose interruption and/or reduction, antiemetics, and supportive care.
Hyponatremia: Monitor serum sodium levels throughout treatment. Correct for concurrent hyperglycemia and high serum paraprotein levels. Manage with dose interruption, reduction, or discontinuation, and supportive care.
Serious Infection: Monitor for infection and treat promptly.
Neurological Toxicity: Advise patients to refrain from driving and engaging in hazardous occupations or activities until neurological toxicity resolves. Optimize hydration status and concomitant medications to avoid dizziness or mental status changes.
Embryo–Fetal Toxicity: Can cause fetal harm. Advise females of reproductive potential and males with a female partner of reproductive potential, of the potential risk to a fetus and use of effective contraception.
Cataract: Cataracts may develop or progress. Treatment of cataracts usually requires surgical removal of the cataract.
Adverse Reactions
The most common adverse reactions (≥20%) in patients with multiple myeloma who receive XVd are fatigue, nausea, decreased appetite, diarrhea, peripheral neuropathy, upper respiratory tract infection, decreased weight, cataract and vomiting. Grade 3–4 laboratory abnormalities (≥10%) are thrombocytopenia, lymphopenia, hypophosphatemia, anemia, hyponatremia and neutropenia. In the BOSTON trial, fatal adverse reactions occurred in 6% of patients within 30 days of last treatment. Serious adverse reactions occurred in 52% of patients. Treatment discontinuation rate due to adverse reactions was 19%.
The most common adverse reactions (≥20%) in patients with multiple myeloma who receive Xd are thrombocytopenia, fatigue, nausea, anemia, decreased appetite, decreased weight, diarrhea, vomiting, hyponatremia, neutropenia, leukopenia, constipation, dyspnea and upper respiratory tract infection. In the STORM trial, fatal adverse reactions occurred in 9% of patients. Serious adverse reactions occurred in 58% of patients. Treatment discontinuation rate due to adverse reactions was 27%.
The most common adverse reactions (incidence ≥20%) in patients with DLBCL, excluding laboratory abnormalities, are fatigue, nausea, diarrhea, appetite decrease, weight decrease, constipation, vomiting, and pyrexia. Grade 3–4 laboratory abnormalities (≥15%) are thrombocytopenia, lymphopenia, neutropenia, anemia, and hyponatremia. In the SADAL trial, fatal adverse reactions occurred in 3.7% of patients within 30 days, and 5% of patients within 60 days of last treatment; the most frequent fatal adverse reactions was infection (4.5% of patients). Serious adverse reactions occurred in 46% of patients; the most frequent serious adverse reaction was infection (21% of patients). Discontinuation due to adverse reactions occurred in 17% of patients.