The U.S. Food and Drug Administration (FDA) greenlit Karyopharm Therapeutics’ Xpovio (selinexor) for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) under accelerated approval.
Specifically, the FDA approved the new indication for Xpovio as a treatment for relapsed or refractory DLBCL that has not been otherwise specified, including DLBCL arising from follicular lymphoma, after at least two lines of systemic therapy. Last year the FDA approved Xpovio in combination with dexamethasone for the treatment of patients with relapsed refractory multiple myeloma who have received at least three prior therapies and whose disease is refractory to at least one proteasome inhibitor, one immunomodulatory agent and one anti-CD38 monoclonal antibody. With this latest approval, Karyopharm said Xpovio, a first-in-class, Selective Inhibitor of Nuclear Export (SINE) compound, is now the first and only drug approved for both of these hematologic indications. Xpovio received Fast Track and Orphan Designation from the FDA for this patient population.
Sharon Shacham, president and chief scientific officer of Karyopharm, said the latest approval for Xpovio is a significant milestone for DLBCL patients who have had limited options for their treatment.
“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,” Shacham said in a statement.
Karyopharm Chief Executive Officer Michael G. Kauffman said the company will initiate the commercial launch of Xpovio in this indication immediately in order to get the medication in the hands of cancer patients who need the treatment.
“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.,” Kauffman said.
The latest approval for Xpovio was based on the Phase IIb SADAL (Selinexor Against Diffuse Aggressive Lymphoma) study that demonstrated a 29% overall response rate in a 134 patient trial. Of those ORR successes, 13% had a complete response and 16% had partial responses. Key secondary endpoints included a median duration of response (DOR) in the responding patients. In the responding patients, 56% maintained a response at three months, 38% at six months, and 15% at 12 months.
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 up to three prior treatments for DLBCL.
A Marketing Authorization Application for Xpovio for relapsed or refractory DLBCL will be submitted to the European Medicines Agency in 2021.