Full Press Release Details
Karyopharm Announces Phase 3 BOSTON Study Meets Primary Endpoint with Significant Increase in
Progression-Free Survival in Patients with Multiple Myeloma Following One to Three Prior Lines of Therapy
Once-Weekly XPOVIO (selinexor), Once-Weekly Velcade (bortezomib) plus Dexamethasone (SVd) Results in Statistically Significant
Reduction in the Risk of Disease Progression or Death Compared to Standard Twice-Weekly Velcade plus Dexamethasone (Vd) Regimen
47% Increase in Median PFS on SVd versus Vd
Regulatory Submission Planned in 2Q 2020; Data to be Submitted for Presentation at Upcoming Medical Meetings
Management to Host Conference Call Today at 8:30 AM ET
NEWTON, Mass. March 2, 2020 Karyopharm Therapeutics Inc. (Nasdaq:KPTI), an oncology-focused pharmaceutical company, today announced
positive top-line results from the randomized Phase 3 BOSTON study evaluating once-weekly XPOVIO (selinexor) in combination with once-weekly Velcade (bortezomib) and low-dose dexamethasone (SVd) compared to standard twice-weekly Velcade plus low-dose dexamethasone
(Vd) in patients with multiple myeloma who have received one to three prior lines of therapy. The BOSTON study met its primary endpoint of a statistically significant increase in progression-free survival (PFS). 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 full top-line data will be submitted for presentation at upcoming medical meetings.
thrilled to report these highly significant top-line results from the BOSTON study, the first randomized Phase 3 trial to demonstrate clinically and statistically significant activity of once-weekly XPOVIO in
combination with a current standard of care treatment in patients with myeloma after one to three prior therapies, said Sharon Shacham, PhD, MBA, President and Chief Scientific Officer of Karyopharm. In the study, patients on the SVd
regimen lived 47% longer without their disease worsening, which we believe represents an important improvement in the treatment of patients with relapsed or refractory multiple myeloma. We plan to submit the full data set for presentations at
upcoming medical meetings to share the results with the medical community. We also intend to submit these data as quickly as possible to the U.S. Food and Drug Administration (FDA) as part of a supplemental New Drug Application seeking to expand the
approved indication for XPOVIO into second line treatment for patients with relapsed or refractory multiple myeloma. If approved, the SVd regimen would be the first and only FDA-approved combination drug
regimen that includes once-weekly Velcade therapy for relapsed myeloma.
XPOVIO received accelerated approval from the FDA on July 3, 2019 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. 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 a confirmatory trial.
Karyopharm expects to submit data from the Phase 3 BOSTON study to serve as this confirmatory trial. The full Prescribing Information for XPOVIO is available at www.XPOVIO.com.
About the BOSTON Study
BOSTON is a Phase 3 randomized, active comparator-controlled, open-label, multicenter study that is designed to compare the efficacy, safety and certain
health-related quality of life (HR-QoL) parameters of once-weekly XPOVIO (selinexor) in combination with once-weekly Velcade (bortezomib) plus low-dose
dexamethasone (SVd) versus twice-weekly Velcade plus low-dose dexamethasone (Vd) in adult patients with relapsed or refractory multiple myeloma who have received one to three prior lines of therapy. The BOSTON
study enrolled approximately 402 patients. The primary endpoint of the study is progression-free survival (PFS) and key secondary endpoints include overall response rate (ORR), among others. Additionally, the BOSTON study allows for patients on the
Vd control arm to crossover to the SVd arm following objective (quantitative) progression of disease. The BOSTON study is being conducted at over 150 clinical sites internationally.
Vd is a standard therapy for previously treated patients with multiple myeloma that is given by injection twice-weekly. Unlike other drugs used to treat
multiple myeloma, selinexor is taken orally. Patients randomized to the SVd arm received selinexor (100mg once-weekly), Velcade (1.3 mg/m2 once-weekly given subcutaneously) and dexamethasone (40mg
weekly). Patients randomized to the Vd arm received Velcade (twice-weekly) plus low-dose dexamethasone (standard therapy given on the recommended
Conference Call Information
will host a conference call today, Monday, March 2, 2020, at 8:30 a.m. Eastern Time, to discuss the top-line results from the BOSTON study. To access the conference call, please dial (855) 437-4406 (local) or (484) 756-4292 (international) at least 10 minutes prior to the start time and refer to conference 3515858. A live audio webcast of the call will be
available under Events & Presentations in the Investor section of the Company s website, http://investors.karyopharm.com/events-presentations. An archived webcast will be available on the Company s website
approximately two hours after the event.
About Multiple Myeloma
According to the National Cancer Institute (NCI), multiple myeloma is the second most common blood cancer in the U.S. with more than 32,000 new cases each year
and over 130,000 patients living with the disease. Despite recent therapeutic advances, there is currently no cure and most patients disease will typically progress following treatment with currently available therapies. According to the NCI,
nearly 13,000 deaths due to multiple myeloma were expected in the U.S. in 2019.
XPOVIO is a first-in-class, oral Selective Inhibitor of
Nuclear Export (SINE) compound. XPOVIO functions by selectively binding to and inhibiting the nuclear export protein exportin 1 (XPO1, also called CRM1). XPOVIO blocks the nuclear export of tumor suppressor, growth regulatory and anti-inflammatory
proteins, leading to accumulation of these proteins in the nucleus and enhancing their anti-cancer activity in the cell. The forced nuclear retention of these proteins can counteract a multitude of the oncogenic pathways that, unchecked, allow
cancer cells with severe DNA damage to continue to grow and divide in an unrestrained fashion. Karyopharm
received accelerated U.S. Food and Drug Administration (FDA) approval of XPOVIO in July 2019 in combination
with dexamethasone for the treatment of adult patients with relapsed refractory multiple myeloma (RRMM) 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. Karyopharm has also submitted a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) with a request for conditional approval of selinexor. A supplemental New
Drug Application was recently submitted to the FDA seeking accelerated approval for selinexor as a new treatment for patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), and selinexor
has received Fast Track and Orphan designation from the FDA for this patient population. Selinexor is also being evaluated in several other mid-and later-phase clinical trials across multiple cancer
indications, including in multiple myeloma in a pivotal, randomized Phase 3 study in combination with Velcade (bortezomib) and low-dose dexamethasone
(BOSTON), as a potential backbone therapy in combination with approved therapies (STOMP), in liposarcoma (SEAL) and in endometrial cancer (SIENDO), among others. Additional Phase 1, Phase 2 and Phase 3 studies are ongoing or currently planned,
including multiple studies in combination with approved therapies in a variety of tumor types to further inform Karyopharm s clinical development priorities for selinexor. Additional clinical trial information for selinexor is available at
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
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 Toxicity
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
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.
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/Weight Loss
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.
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 Toxicity
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.
Embryo-Fetal Toxicity
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