On May 5, 2022 Karyopharm Therapeutics Inc. (Nasdaq:KPTI), a commercial-stage pharmaceutical company pioneering novel cancer therapies, reported financial results for the quarter ended March 31, 2022 (Press release, Karyopharm, MAY 5, 2022, View Source [SID1234613669]). 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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"During the first quarter of 2022, we continued to drive further patient benefit by expanding the use of XPOVIO in the 2nd to 4th line setting and, despite headwinds caused by the Omicron variant, we achieved strong XPOVIO sales of 30% year-over-year growth," said Richard Paulson, President and Chief Executive Officer of Karyopharm. "As we advance our clinical pipeline across four core priority areas, we look forward to presenting the preliminary results from our Phase 1/2 frontline myelofibrosis study and initiating our Phase 3 study in the p53 wild-type endometrial cancer patient population in the second half of 2022, both areas with significant unmet need."
First Quarter 2022 and Recent Highlights
XPOVIO Commercial Performance
Achieved U.S. net product revenue for the first quarter of 2022 of $28.3 million, a 30% increase compared to the first quarter of 2021.
COVID related impact in January and February on oncology patient visits, which improved in March.
Continued positive shift in patients to earlier lines from the penta-refractory setting.
Recent regulatory approvals in Australia and Singapore received by partner Antengene Therapeutics Limited further expands selinexor’s reach to patients around the world, following approval in Mainland China in December 2021.
R&D Highlights for Selinexor and Eltanexor
Abstracts highlighting selinexor clinical research have been selected for presentation at the upcoming American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2022 Annual Meeting during June 3-7, 2022, including a poster presentation highlighting preliminary results from a Phase 1/2 trial evaluating selinexor in combination with ruxolitinib in patients with treatment-naïve myelofibrosis and an oral presentation discussing subgroup analyses and molecular classification data from the Phase 3 SIENDO study evaluating selinexor in endometrial cancer.
Results from the prospective double-blind, randomized Phase 3 SIENDO study of oral selinexor versus placebo as maintenance therapy after first-line chemotherapy for advanced or recurrent endometrial cancer were presented at the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper)’s Virtual Plenary and the Society for Gynecologic Oncology 2022 Annual Meeting on Women’s Cancer in March 2022.
In a preliminary analysis of a pre-specified, exploratory sub-group of patients with advanced or recurrent p53 wild-type endometrial cancer in the SIENDO trial, a 10 month improvement in median progression free survival was observed with selinexor versus placebo: 13.7 months in the selinexor arm (n=67) vs 3.7 months in the placebo arm (n=36).
The Company plans to initiate a new randomized, placebo-controlled clinical study of selinexor in patients with p53 wild-type endometrial cancer during the second half of 2022 and top-line data are expected to be available in the first half of 2024.
The U.S. Food and Drug Administration (FDA) granted orphan drug designation for eltanexor for the treatment of myelodysplastic syndromes (MDS). The Company is currently evaluating the use of eltanexor in a Phase 2 study as monotherapy in hypomethylating agent (HMA)-refractory, intermediate or high-risk MDS and also exploring its use in combination with HMA therapy in newly diagnosed patients in a Phase 1 study.
The application for NEXPOVIO️ (selinexor) in combination with Velcade️ (bortezomib) and low-dose dexamethasone for the treatment of multiple myeloma following at least one prior therapy, is currently under review by the Committee for Medicinal Products for Human Use (CHMP). The CHMP is expected to issue an opinion to the European Commission in the first half of 2022.
Corporate and Business Highlights
Announced the appointment of Reshma Rangwala, MD, PhD, as Chief Medical Officer.
Announced the further transition of company co-founders Sharon Shacham, PhD, MBA, and Michael Kauffman, MD, PhD, who will step down from their respective roles as Chief Scientific Officer and Senior Clinical Advisor as of May 31, 2022. Dr. Shacham will continue to serve on Karyopharm’s Scientific Advisory Board and will serve in an advisory capacity.
First Quarter 2022 Financial Results
Total Revenues: Total revenue for the first quarter of 2022 was $47.7 million, up 105% compared to $23.3 million for the first quarter of 2021.
Net product revenue: Net product revenue for the first quarter of 2022 was $28.3 million, up 30% compared to $21.7 million for the first quarter of 2021.
License and other revenue: License and other revenue for the first quarter of 2022 was $19.4 million, compared to $1.5 million for the first quarter of 2021. The increase in license and other revenue in the first quarter of 2022 compared to the first quarter of 2021 was primarily attributable to $8.6 million in revenue recognized related to milestones earned in connection with our license agreements with Antengene Therapeutics Limited and Promedico Ltd., coupled with $7.1 million earned in reimbursement of development expenses from the Menarini Group.
Cost of sales: Cost of sales for the first quarter of 2022 were $1.4 million, compared to $0.9 million for the first quarter of 2021. 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 first quarter of 2022 were $42.1 million, compared to $37.1 million for the first quarter of 2021. The increase in R&D expenses in the first quarter of 2022 compared to the first quarter of 2021 was primarily attributable to higher clinical trial expenses.
Selling, general and administrative (SG&A) expenses: SG&A expenses for the first quarter of 2022 were $38.8 million, compared to $37.7 million for the first quarter of 2021.
Interest expense: Interest expense for the first quarter of 2022 was $6.7 million, compared to $5.1 million for the first quarter of 2021. The increase in interest expense in the first quarter of 2022 compared to the first quarter of 2021 was related to the deferred royalty obligation following Karyopharm’s June 2021 amendment of its Revenue Interest Agreement with HealthCare Royalty Management, LLC.
Net loss: Karyopharm reported a net loss of $41.4 million, or $0.53 per share, for the first quarter of 2022, compared to a net loss of $57.4 million, or $0.77 per share, for the first quarter of 2021. Net loss included non-cash stock-based compensation expense of $7.3 million and $7.4 million for the first quarters of 2022 and 2021, respectively.
Cash position: Cash, cash equivalents, restricted cash and investments as of March 31, 2022 totaled $207.0 million, compared to $235.6 million as of December 31, 2021.
2022 Financial Outlook
Based on its current operating plans, Karyopharm reaffirms 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 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, May 5, 2022, at 8:30 a.m. Eastern Time, to discuss the first quarter 2022 financial results and 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 2 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.