$KPTI - Karyopharm Announces FDA Approval of XPOVIO(R) (selinexor) for the Treatment of Patients with Relapsed or Refractory Diffuse Large B-cell Lymphoma (DLBCL)
11:25 AM ET 6/22/20 | GlobeNewswire
Karyopharm Announces FDA Approval of XPOVIO(R) (selinexor) for the Treatment of Patients with Relapsed or Refractory Diffuse Large B-cell Lymphoma (DLBCL)
-- XPOVIO is Now the Only Single-Agent, Oral Therapy Approved for the Treatment of Patients with Relapsed or Refractory Diffuse Large B-cell Lymphoma, Including DLBCL Arising from Follicular Lymphoma --
-- XPOVIO is the First and Only FDA-Approved Drug for Use in Both Multiple Myeloma and DLBCL --
-- Conference Call Scheduled for Today at 12:30 p.m. Eastern Time --
NEWTON, Mass., June 22, 2020 (GLOBE NEWSWIRE) -- Karyopharm Therapeutics Inc. (Nasdaq:KPTI), an innovation-driven pharmaceutical company, today announced that the U.S. Food and Drug Administration (FDA) has approved oral XPOVIO(R) (selinexor), the Company's first-in-class, Selective Inhibitor of Nuclear Export (SINE) compound, 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 was approved based on response rate under the FDA's Accelerated Approval Program, which was developed to allow for expedited approval of drugs that treat serious conditions and that fill an unmet medical need. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).
XPOVIO will be commercially available immediately in this new indication in the U.S. and Karyopharm will leverage its existing commercial infrastructure to market this second oncology indication. A Marketing Authorization Application for selinexor for relapsed or refractory DLBCL is planned for submission to the European Medicines Agency in 2021.
"The accelerated approval of oral XPOVIO in patients with relapsed or refractory DLBCL is a significant milestone for the patients and families who currently have limited treatment options available for their disease," said Sharon Shacham, PhD, MBA, Founder, President and Chief Scientific Officer of Karyopharm. "This approval marks the first for an oral agent for patients with previously treated DLBCL and the first approval of any single drug for this highly aggressive type of lymphoma. Additionally, this is now the second commercial oncology indication for XPOVIO, highlighting its novel mechanism of action, ease of administration and ability to produce rapid and durable responses in patients with heavily pretreated disease. We share this tremendous achievement with the patients, employees, caregivers and physicians who have tirelessly contributed to the advancement of XPOVIO from its original discovery and clinical development to today's second FDA approval."
"For the significant number of patients with relapsed or refractory DLBCL, there is an important need for new therapies for this particularly vulnerable patient population. Unfortunately, despite often multiple types of chemotherapy and targeted-drug combination therapy, many patients have disease which continues to progress," said John P. Leonard, MD, the Richard T. Silver Distinguished Professor of Hematology and Medical Oncology at Weill Cornell Medicine and an oncologist at NewYork-Presbyterian/Weill Cornell Medical Center.(1) "Single agent, oral XPOVIO demonstrated a clinically meaningful overall response rate of 29%, including a complete response rate of 13%, in the pivotal SADAL study across several disease subtypes. Importantly, some patient responses were durable with 38% of responding patients maintaining a response at 6 months. The clinical profile and tolerability of oral XPOVIO provides physicians and patients with a new treatment alternative to traditional intravenous chemotherapy regimens."
"We will initiate our XPOVIO commercial launch efforts in DLBCL immediately, expanding our reach across the country for cancer patients in need," said Michael G. Kauffman, MD, PhD, Chief Executive Officer of Karyopharm. "Since our founding in 2008, Karyopharm has been focused on exploring the potential of nuclear transport modulators and we are thrilled to now enter this new chapter of growth with our dual-commercialization of the first and only nuclear export inhibitor approved in the U.S."
About the Phase 2b SADAL Study
The accelerated FDA approval of XPOVIO is based on the results from the multi-center, single-arm Phase 2b SADAL (Selinexor Against Diffuse Aggressive Lymphoma) study (NCT02227251), which evaluated 134 patients (median of 2 prior systemic therapies with a range of 1-5) with relapsed or refractory DLBCL. Patients were administered a fixed 60 mg dose of XPOVIO given orally twice weekly for a four-week cycle. Patients with germinal center B-cell (GCB) or non-GCB subtypes of DLBCL were included in enrollment.
The SADAL study met its primary endpoint of overall response rate (ORR) with an ORR of 29%, including 18 (13%) complete responses (CRs) and 21 (16%) partial responses (PRs).
Key secondary endpoints included a median duration of response (DOR) in the responding patients. In the responding patients, 56% maintained a response at 3 months, 38% at 6 months and 15% at 12 months.
All 134 patients were included in the safety analyses. The most common treatment-related adverse events (AEs) were cytopenias along with gastrointestinal and constitutional symptoms and were generally reversible and managed with dose modifications and/or standard supportive care. The most common non-hematologic AEs were fatigue (63%), nausea (57%), decreased appetite (37%), and diarrhea (37%), and were mostly Grade 1 and 2 events. Grade 3 and 4 laboratory abnormalities in >=15% of patients included thrombocytopenia, lymphopenia, neutropenia, anemia, and hyponatremia. Grade 4 laboratory abnormalities in >=5% of patients were thrombocytopenia (18%), lymphopenia (5%), and neutropenia (9%).
As part of the FDA accelerated approval, the FDA has agreed that the XPORT-DLBCL-030 study could serve as the confirmatory trial for evaluating selinexor in DLBCL. This trial will assess the effect of selinexor or placebo added to a standard backbone immunochemotherapy of rituximab-gemcitabine-dexamethasone-platinum (R-GDP) in patients with 1-3 prior treatments for DLBCL. The rationale for this study is based on data from the ongoing Phase 1B study being conducted by the French Lymphoma Academic Research Organization (LYSARC) (NCT02741388). Karyopharm anticipates the XPORT-DLBCL-030 study will begin by the end of 2020.
Conference Call Information
Karyopharm will host a conference call today, Monday, June 22, 2020, at 12:30 p.m. Eastern Time, to discuss the FDA's approval of XPOVIO for the treatment of patients with relapsed or refractory DLBCL. 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 ID 8794658. 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 XPOVIO(R) (selinexor)
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 in this same RRMM indication. Karyopharm submitted a supplemental New Drug Application (sNDA) to the FDA requesting an expansion of its current indication to include the treatment for patients with multiple myeloma after at least one prior line of therapy based on the positive results from the Phase 3 BOSTON study which evaluated selinexor in combination with Velcade(R) (bortezomib) and low-dose dexamethasone. In June 2020, Karyopharm received accelerated FDA approval of XPOVIO for its second indication in 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. Selinexor is also being evaluated in several other mid-and later-phase clinical trials across multiple cancer indications, including as a potential backbone therapy in combination with approved myeloma 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 www.clinicaltrials.gov.
For more information about Karyopharm's products or clinical trials, please contact the Medical Information department at:
Tel: +1 (888) 209-9326
Email: medicalinformation@karyopharm.com
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