“I am extremely proud of the significant progress we have made thus far in 2020. Following our recent announcement of the positive top-line results from the pivotal Phase 3 BOSTON study, we are actively preparing to share the dataset at the
First Quarter 2020 and Recent Highlights
XPOVIO in Multiple Myeloma
- Pivotal Phase 3 BOSTON Study Met Primary Endpoint. In early
March 2020, Karyopharm announced the top-line results from the BOSTONstudy, including that BOSTONmet its primary endpoint of a statistically significant increase in progression-free survival (PFS). 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. The median PFS in the SVd arm was 13.93 months compared to 9.46 months in the Vd arm, representing a 4.47 month (47%) increase in median PFS (hazard ratio=0.70; p=0.0066). There were no new safety signals on the SVd arm and there was no imbalance in deaths between the two arms in the study. The clinical data will be disclosed in an oral presentation at the ASCO 2020 Virtual Scientific Program taking place May 29-31, 2020. Karyopharm expects to submit an sNDA to the FDA by the end of May 2020requesting expansion of the currently approved indication for XPOVIO to include second line treatment for patients with relapsed or refractory multiple myeloma. A regulatory submission to the European Medicines Agency(EMA) is also planned.
U.S.Commercialization. Oral XPOVIO became commercially available to patients in the U.S.in July 2019and generated net product sales of $16.1 millionin the first quarter of 2020. As of March 31, 2020, more than 2,200 XPOVIO prescriptions have been filled since launch, and more than 150 new physician prescribing accounts were added in the first quarter. Prescription refills for XPOVIO among existing patients remained strong in the quarter. Based on data from specialty pharmacies, approximately 60% of eligible patients have received a refill for their second prescription since launch, and the per patient average number of prescriptions continues to increase each quarter. Additionally, for those patients responding well to therapy, we continue to see an increasing and meaningful number of patients who have now been on therapy for five months or longer, further supporting the potential for longer-term use of XPOVIO therapy, as appropriate. We did experience a decrease in net product sales in the first quarter of 2020 compared to the fourth quarter of 2019, largely driven by minimal channel inventory build in the first quarter. Finally, there were fewer new patient XPOVIO starts than expected in the quarter, primarily due to the diversion of physician and other healthcare resources to manage the ongoing COVID-19 pandemic and the significant reduction in Karyopharm’s field force in-person activities as a result of shelter-in-place orders across the U.S.However, we were encouraged to see an acceleration in demand for XPOVIO in April 2020.
- Decision from EMA for Marketing Authorization Application (MAA) Expected in 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. In January 2020, Karyopharm was granted a three-month extension from the EMA’s Committee for Medicinal Products for Human Use (CHMP) to provide additional time to respond to the outstanding questions from the MAA, primarily re-monitoring certain clinical data. Due to the COVID-19 pandemic and the resulting disruption at many clinical sites, re-monitoring activities requested by CHMP remain ongoing. The Company does not anticipate any significant changes to the data sets supporting the MAA filing from the ongoing re-monitoring activities. The Company now expects to be able to respond to CHMP in mid-2020 and to receive a decision on the selinexor MAA by late-2020.
Selinexor in Diffuse Large B-Cell Lymphoma (DLBCL)
- FDA Accepts sNDA and Grants Priority Review. The FDA accepted for filing with Priority Review Karyopharm’s sNDA seeking accelerated approval for selinexor for the treatment of adult patients with relapsed or refractory DLBCL, not otherwise specified, who have received at least two prior therapies. The FDA assigned an action date of
June 23, 2020under the Prescription Drug User Fee Act (PDUFA). The Company also expects to submit an MAA to the EMA in 2021 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 FDA in 2018.
Low Dose Selinexor in COVID-19
- First Patient Dosed in Randomized Study. Karyopharm recently announced the initiation of a new study to evaluate low dose oral selinexor in hospitalized patients with severe COVID-19. SINE compounds, including both selinexor and it’s close relative verdinexor, have been identified as having the potential to interfere with key host protein interactions with influenza, RSV and other viruses, including SARS-CoV-2, the virus that causes COVID-19. Furthermore, XPO1 (also called CRM1) was identified as one of the host proteins with the highest number of functional connections with SARS-CoV proteins. Recent preclinical experiments have further demonstrated selinexor’s ability to inhibit the viral propagation of the SARS-CoV-2 virus in monkey
Verocells, which are commonly used to study human viral infections. Finally, SINE compounds, including selinexor, have demonstrated potent anti-inflammatory activity through the inhibition of Nuclear Factor kB (NF-kB), leading to reductions in cytokines such as IL6, IL1, IFNγ and others in a variety of models. Since high levels of these cytokines are found in patients with COVID-19 and the most severe disease, reductions in these cytokines may be particularly beneficial to hospitalized patients with COVID-19. Patient enrollment and dosing has begun in this randomized, placebo-controlled, Phase 2 study (XPORT-CoV-1001 / NCT04349098), which is expected to enroll approximately 230 patients at clinical sites in the U.S., Europe, and Israel.
Corporate and Financial Updates
- Expanded Territory Rights with
Antengene Corporationand Reacquisition of Rights from Ono Pharmaceutical Co., Ltd. Karyopharm’s license agreement with Antengene, our current partner in China, was amended to provide Antengene with the exclusive right to develop and commercialize selinexor and eltanexor in all human oncology indications in Australia, New Zealand, South Korea, Taiwan, Hong Kongand the ASEANcountries. The amended agreement also includes the development and commercialization of KPT-9274 in all human oncology indications and verdinexor in human non-oncology indications in Australia and New Zealand. Under the terms of the amended agreement, Karyopharm will receive a one-time upfront payment of $12.0 millionfrom Antengene, expected in the second quarter of 2020. Karyopharm is eligible to receive additional payments if certain future prespecified regulatory and commercial milestones are achieved by Antengene. Karyopharm is also eligible to receive tiered double-digit royalties based on future net sales of selinexor and eltanexor, and tiered single-to double-digit royalties based on future net sales of verdinexor and KPT-9274 in the expanded territory.
Certain countries in the expanded territory with Antengene became available following Karyopharm’s reacquisition of the exclusive development and commercial rights from Ono which were transferred to Karyopharm in
April 2020at no cost to Karyopharm. Karyopharm has chosen to retain the rights to selinexor and eltanexor in Japanwhile granting Antengene the exclusive rights to develop and commercialize selinexor and eltanexor in South Korea, Taiwan, Hong Kongand the ASEANcountries.
Outside of the territories licensed by Antengene, and the market for selinexor in
Israel, Karyopharm maintains complete development and commercial rights to selinexor and eltanexor throughout the world, including in the U.S., Canada, Europe, Japan, and Latin America.
- Strengthened the Balance Sheet with a Public Equity Offering. On
March 6, 2020, Karyopharm completed an underwritten public offering of 7,187,500 shares of its common stock at a price to the public of $24.00per share. The net proceeds of $161.8 millionfrom the offering will be used to support key research and development and commercial initiatives, including potential future product launches.
- Collaboration Agreement with
Curadev Pharma Pvt Ltd(Curadev). Karyopharm and Curadev, a privately-owned biotechnology company, have entered into a strategic collaboration to identify and co-develop novel small molecules against various biological targets for the treatment of cancer and other major diseases. Under the terms of the agreement, Karyopharm and Curadev have agreed to identify and develop small molecules against up to two targets. Curadev will conduct exploratory research, drug discovery and development for designated programs up to the conclusion of preclinical proof of concept studies, after which Karyopharm will have an option to an exclusive license to develop and commercialize each target on a global basis. Karyopharm and Curadev will co-fund and jointly oversee development up to the option exercise period.
- Key Appointments to the Executive Leadership Team and Board of Directors. During the first quarter of 2020, Karyopharm appointed
John Demareeas Chief Commercial Officer and its Board of Directors elected Richard Paulsonas a director. Mr. Demareebrings more than 20 years of oncology experience, building commercial capabilities and leading multiple successful product launches. Mr. Paulsoncurrently serves as Executive Vice President and Chief Executive Officer of Ipsen North Americaand brings over 25 years of global biopharmaceutical industry experience, including launching best-in-class oncology medicines.
First Quarter 2020 Financial Results
Net product revenue: Net product revenue for the first quarter of 2020 was
License and other revenue: License and other revenue for the first quarter of 2020 was
Cost of sales: Cost of sales were
Research and development expenses (R&D): R&D expenses for the first quarter of 2020 were
Selling, general and administrative expenses (SG&A): For the first quarter of 2020, SG&A expenses were
Interest expense: Interest expense for the first quarter of 2020 was
Net loss: Karyopharm reported a net loss of
Cash position: Cash, cash equivalents, restricted cash and investments as of
2020 Financial Outlook
Karyopharm expects XPOVIO net product sales to be slightly higher in the second quarter of 2020 as compared to the first quarter of 2020. In addition, total revenues are expected to be higher due to an increase in collaboration revenue from the expanded territory agreement with Antengene. The Company will not be issuing XPOVIO revenue guidance for the full year 2020 as it continues to monitor the ongoing commercial impact from the COVID-19 pandemic as well as the timing of key expected regulatory actions in 2020. These regulatory events include the potential approval of XPOVIO for patients with relapsed or refractory DLBCL as well as Karyopharm’s planned sNDA submission, and subsequent FDA-review period, requesting expansion of the approved indication for XPOVIO to include second line treatment for patients with relapsed or refractory multiple myeloma.
Based on its current operating plans, including the reduction of some R&D costs as a result of trial delays due to the ongoing COVID-19 pandemic, Karyopharm expects its non-GAAP R&D and SG&A expenses, which excludes stock-based compensation expense, for the full year 2020 to be at the lower end of the previously projected 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 2022.
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,
IMPORTANT SAFETY INFORMATION
XPOVIO can cause thrombocytopenia, leading to potentially fatal hemorrhage. Thrombocytopenia was reported as an adverse reaction in 74% of patients, and severe (Grade 3-4) thrombocytopenia occurred in 61% of patients treated with XPOVIO. The median time to onset of the first event was 22 days. Bleeding occurred in 23% of patients with thrombocytopenia, clinically significant bleeding occurred in 5% of patients with thrombocytopenia and fatal hemorrhage occurred in <1% of patients.
Monitor platelet counts at baseline, during treatment, and as clinically indicated. Monitor more frequently during the first two months of treatment. Institute platelet transfusion and/or other treatments as clinically indicated. Monitor patients for signs and symptoms of bleeding and evaluate promptly. Interrupt and/or reduce dose, or permanently discontinue based on severity of adverse reaction.
XPOVIO can cause neutropenia, potentially increasing the risk of infection. Neutropenia was reported as an adverse reaction in 34% of patients, and severe (Grade 3-4) neutropenia occurred in 21% of patients treated with XPOVIO. The median time to onset of the first event was 25 days. Febrile neutropenia was reported in 3% of patients.
Obtain neutrophil counts at baseline, during treatment, and as clinically indicated. Monitor more frequently during the first two months of treatment. Monitor patients for signs and symptoms of concomitant infection and evaluate promptly. Consider supportive measures including antimicrobials for signs of infection and use of growth factors (e.g., G-CSF). Interrupt and/or reduce dose, or permanently discontinue based on severity of adverse reaction.
Gastrointestinal toxicities occurred in patients treated with XPOVIO.
Nausea was reported as an adverse reaction in 72% of patients, and Grade 3 nausea occurred in 9% of patients treated with XPOVIO. The median time to onset of the first nausea event was 3 days.
Vomiting was reported in 41% of patients, and Grade 3 vomiting occurred in 4% of patients treated with XPOVIO. The median time to onset of the first vomiting event was 5 days.
Provide prophylactic 5-HT3 antagonists and/or other anti-nausea agents, prior to and during treatment with XPOVIO. Manage nausea/vomiting by dose interruption, reduction, and/or discontinuation. Administer intravenous fluids and replace electrolytes to prevent dehydration in patients at risk. Use additional anti-nausea medications as clinically indicated.
Diarrhea was reported as an adverse reaction in 44% of patients, and Grade 3 diarrhea occurred in 6% of patients treated with XPOVIO. The median time to onset of diarrhea was 15 days.
Manage diarrhea by dose modifications and/or standard anti-diarrheal agents; administer intravenous fluids to prevent dehydration in patients at risk.
Anorexia was reported as an adverse reaction in 53% of patients, and Grade 3 anorexia occurred in 5% of patients treated with XPOVIO. The median time to onset of anorexia was 8 days.
Weight loss was reported as an adverse reaction in 47% of patients, and Grade 3 weight loss occurred in 1% of patients treated with XPOVIO. The median time to onset of weight loss was 15 days.
Monitor patient weight at baseline, during treatment, and as clinically indicated. Monitor more frequently during the first two months of treatment. Manage anorexia and weight loss with dose modifications, appetite stimulants, and nutritional support.
XPOVIO can cause hyponatremia; 39% of patients treated with XPOVIO experienced hyponatremia, 22% of patients experienced Grade 3 or 4 hyponatremia. The median time to onset of the first event was 8 days.
Monitor sodium level at baseline, during treatment, and as clinically indicated. Monitor more frequently during the first two months of treatment. Correct sodium levels for concurrent hyperglycemia (serum glucose >150 mg/dL) and high serum paraprotein levels. Treat hyponatremia per clinical guidelines (intravenous saline and/or salt tablets), including dietary review. Interrupt and/or reduce dose, or permanently discontinue based on severity of adverse reaction.
In patients receiving XPOVIO, 52% of patients experienced any grade of infection. Upper respiratory tract infection of any grade occurred in 21%, pneumonia in 13%, and sepsis in 6% of patients. Grade ≥3 infections were reported in 25% of patients, and deaths resulting from an infection occurred in 4% of patients. The most commonly reported Grade ≥3 infections were pneumonia in 9% of patients, followed by sepsis in 6%. The median time to onset was 54 days for pneumonia and 42 days for sepsis. Most infections were not associated with neutropenia and were caused by non-opportunistic organisms.
Neurological toxicities occurred in patients treated with XPOVIO.
Neurological adverse reactions including dizziness, syncope, depressed level of consciousness, and mental status changes (including delirium and confusional state) occurred in 30% of patients, and severe events (Grade 3-4) occurred in 9% of patients treated with XPOVIO. Median time to the first event was 15 days.
Optimize hydration status, hemoglobin level, and concomitant medications to avoid exacerbating dizziness or mental status changes.
Based on data from animal studies and its mechanism of action, XPOVIO can cause fetal harm when administered to a pregnant woman. Selinexor administration to pregnant animals during organogenesis resulted in structural abnormalities and alterations to growth at exposures below those occurring clinically at the recommended dose.
Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential and males with a female partner of reproductive potential to use effective contraception during treatment with XPOVIO and for 1 week after the last dose.
The most common adverse reactions (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%.
Please see XPOVIO Full Prescribing Information 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 and plans relating to selinexor as a potential treatment for patients with COVID-19; the design and execution of Karyopharm’s clinical trials to study this potential application of selinexor, including the dosing regimen; the potential anti-viral and anti-inflammatory properties of selinexor; XPOVIO for the treatment of patients with heavily pretreated multiple myeloma or relapsed or refractory diffuse large B-cell lymphoma; commercialization of XPOVIO or any of its drug candidates and the commercial performance of XPOVIO; submissions to, and the review and potential approval of selinexor by, regulatory authorities, including the anticipated availability of data to support such submissions, timing of such submissions and actions by regulatory authorities and the potential availability of accelerated approval pathways; the therapeutic potential of and potential clinical development plans for Karyopharm's drug candidates, especially selinexor; 2020 financial expectations, including forecasted non-GAAP R&D and SG&A expenses; and expectations of the sufficiency of Karyopharm’s existing cash and investments. 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 confirmatory approval in the
Velcade® is a registered trademark of Takeda Pharmaceutical Company Limited.
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KARYOPHARM THERAPEUTICS INC.
CONDENSED CONSOLIDATED STATEMENTS OF OPERATIONS
(in thousands, except per share amounts)
|Three Months Ended,
|Product revenue, net||$||16,061||$||—|
|License and other revenue||2,077||155|
|Cost of sales||819||—|
|Research and development||33,997||37,974|
|Selling, general and administrative||30,678||27,103|
|Total operating expenses||65,494||65,077|
|Loss from operations||(47,356||)||(64,922||)|
|Other income (expense):|
|Other income (expense), net||25||(2||)|
|Total other expense, net||(5,509||)||(1,229||)|
|Loss before income taxes||(52,865||)||(66,151||)|
|Income tax provision||(66||)||(10||)|
|Net loss per share—basic and diluted||$||(0.78||)||$||(1.09||)|
|Weighted-average number of common shares outstanding used in net loss per share—basic and diluted||67,627||60,856|
Karyopharm Therapeutics Inc.
Condensed Consolidated Balance Sheets
|Cash, cash equivalents and investments||$||383,504||$||263,972|
|Property and equipment, net||2,814||3,046|
|LIABILITIES AND STOCKHOLDERS’ EQUITY|
|Convertible senior notes||111,769||109,857|
|Deferred royalty obligation||73,588||73,588|
|Total stockholders’ equity||166,147||49,774|
|Total liabilities and stockholders’ equity; 73,095 and 65,370 shares issued and outstanding at
Source: Karyopharm Therapeutics Inc.