On August 4, 2022 Karyopharm Therapeutics Inc. (Nasdaq:KPTI), a commercial-stage pharmaceutical company pioneering novel cancer therapies, reported business highlights and financial results for the quarter ended June 30, 2022 (Press release, Karyopharm, AUG 4, 2022, View Source [SID1234617454]).
Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
"I’m pleased with our team’s ongoing commitment to successfully execute against key priorities in the second quarter, achieving more than 75% year-over-year revenue growth and further expanding patient access for selinexor globally following full marketing authorization from the European Commission and recent launches in China and Canada," said Richard Paulson, President and Chief Executive Officer of Karyopharm. "Despite headwinds caused by COVID-19 at the beginning of the year and increased competition for later lines of multiple myeloma treatment, we continue to see increased use of XPOVIO in earlier lines with growth in the community setting. Looking ahead to the remainder of the year, we have several key upcoming milestones, including reporting additional data from our studies of selinexor in front-line myelofibrosis and eltanexor in relapsing/refractory myelodysplastic syndromes."
Second Quarter 2022 and Recent Highlights
XPOVIO Commercial Performance
Achieved U.S. net product revenue for the second quarter of 2022 of $29.0 million, a 44% increase compared to the second quarter of 2021, driven by strong year-over-year growth in new patient starts and refills, with continued shift of XPOVIO into second to fourth lines of therapy.
In the second quarter of 2022, a recovery in new patient starts as compared to the previous quarter was offset by the decline in refills due to COVID-19 related reduction of new patient starts in the beginning of the year and intensified late-line competition in the academic setting.
XPOVIO continued its growth in the community setting, driven by a positive shift in perception and intent to treat metrics.
Increased selinexor’s reach to patients around the world with the full marketing authorization of NEXPOVIO (selinexor) in Europe, which expands the indication in multiple myeloma to patients with multiple myeloma after at least one prior therapy as well as commercial launches in mainland China and Canada by partners Antengene Corporation Limited and FORUS Therapeutics Inc., respectively.
Research & Development (R&D) Highlights for Selinexor and Eltanexor
European Commission granted marketing authorization of NEXPOVIO in combination with once weekly bortezomib (Velcade) and low-dose dexamethasone (XVd) for the treatment of adults with multiple myeloma who have received at least one prior therapy, expanding on the prior approval which was in combination with dexamethasone for the treatment of multiple myeloma in adult patients who have received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors, two immunomodulatory agents and an anti-CD38 monoclonal antibody, and who have demonstrated disease progression on the last therapy.
Results from Phase 1/2 study of selinexor in combination with ruxolitinib in treatment-naïve myelofibrosis were presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2022 Annual Meeting, including a generally manageable side effect profile with no dose limiting toxicities and 75% of evaluable patients demonstrating ≥35% spleen volume reduction (SVR 35) at week 12. The most commonly reported Grade 3/4 treatment emergent adverse events were thrombocytopenia (27%), anemia (20%) and neutropenia (20%). These data were also presented at the European Hematology Association (EHA) (Free EHA Whitepaper) 2022 Hybrid Congress.
Following productive discussions with the U.S. Food and Drug Administration (FDA), the Company is finalizing a partner for a companion diagnostic to be used in a registration-enabling study of selinexor in patients with p53 wild-type endometrial cancer.
FDA granted fast track designation for the development program of eltanexor as monotherapy for the treatment of patients with relapsed or refractory intermediate, high-, or very high-risk myelodysplastic syndromes (MDS), per IPSS-R. In addition, the FDA also granted eltanexor orphan drug designation for the treatment of MDS and selinexor for the treatment of myelofibrosis.
The European Commission granted EU orphan medicinal product designation for eltanexor for the treatment of MDS.
2022 Financial Guidance
Based on its current operating plans, Karyopharm is updating its guidance for full year 2022:
Total revenue to be in the range of $155 million to $165 million.
XPOVIO net product revenue to be in the range of $120 million to $130 million versus previous guidance of $135 million to $145 million.
Non-GAAP R&D and Selling, general and administrative (SG&A) expenses, excluding stock-based compensation expense, to be in the range of $250 million to $265 million versus previous guidance 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 continues to expect 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.
Second Quarter 2022 Financial Results
Total Revenues: Total revenue for the second quarter of 2022 was $39.7 million, up 76% compared to $22.6 million for the second quarter of 2021.
Net product revenue: Net product revenue for the second quarter of 2022 was $29.0 million, up 44% compared to $20.2 million for the second quarter of 2021.
License and other revenue: License and other revenue for the second quarter of 2022 was $10.7 million, compared to $2.4 million for the second quarter of 2021. The increase was primarily attributable to $6.5 million earned in reimbursement of development expenses from the Menarini Group.
Cost of sales: Cost of sales for the second quarter of 2022 were $0.9 million, compared to $1.1 million for the second quarter of 2021. Cost of sales reflects the costs of XPOVIO units sold and third-party royalties on net product revenue.
R&D expenses: R&D expenses for the second quarter of 2022 were $44.3 million, compared to $34.0 million for the second quarter of 2021. The increase was primarily driven by an increase in personnel costs and stock-based compensation, including $3.8 million of severance-related stock-based compensation expense incurred during the three months ended June 30, 2022.
SG&A expenses: SG&A expenses for the second quarter of 2022 were $37.3 million, compared to $36.5 million for the second quarter of 2021. The increase in SG&A expenses was primarily due to an increase in stock-based compensation as a result of $3.5 million of severance-related stock-based compensation expense incurred during the three months ended June 30, 2022.
Interest expense: Interest expense for the second quarter of 2022 was $6.3 million, compared to $5.0 million for the second quarter of 2021.
Net loss: Karyopharm reported a net loss of $49.1 million, or $0.62 per share, for the second quarter of 2022, compared to a net loss of $53.6 million, or $0.71 per share, for the second quarter of 2021. Net loss included non-cash stock-based compensation expense of $15.1 million and $8.1 million for the second quarters of 2022 and 2021, respectively.
Cash position: Cash, cash equivalents, restricted cash and investments as of June 30, 2022, totaled $172.6 million, compared to $235.6 million as of December 31, 2021.
Non-GAAP Financial Information
Karyopharm uses a non-GAAP financial measure, 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, August 4, 2022, at 8:00 a.m. Eastern Time, to discuss the second 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 various indications in a growing number of ex-U.S. territories and countries, including but not limited to the European Union, the United Kingdom, China, South Korea, Canada and Israel, and is marketed in those areas by Karyopharm’s global partners.
Please refer to the local Prescribing Information for full details.
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]
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.
Use In Specific Populations
Lactation: Advise not to breastfeed.