Xpovio (selinexor), an oral selective inhibitor of nuclear transport from Karyopharm Therapeutics Inc., of Newton, Mass., received FDA approval today for treating adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), including DLBCL arising from follicular lymphoma, after at least two lines of systemic therapy.
Xpovio will be available immediately in the U.S., the company said, and, due to COVID-19 restrictions, the launch will be a virtual one.
“In terms of launching in the virtual environment, given the pandemic started in Q1, we've known for quite some time that a virtual launch would be necessary, and we've been preparing accordingly,” Ian Karp, Karyopharm’s vice president of investor and public relations, said in this morning’s conference call to investors. “All of our field teams have been provided additional tools to virtually engage with customers. We rapidly launched multiple digital tools to facilitate continued sales force engagement with customers, and the field team has been trained on how to utilize these tools with the appropriate promotional pieces in DLBCL.”
The company plans to submit a marketing authorization application next year to the EMA for selinexor for treating relapsed or refractory DLBCL.
The approval arrived a bit earlier than expected. The PDUFA data for Xpovio was set for tomorrow, June 23, under the FDA’s Accelerated Approval Program.
Xpovio received its first approval in July 2019 as a combination with dexamethasone to treat adults with relapsed 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.
Continued approval for the new indication may be contingent upon verification and description of clinical benefit in a confirmatory trial or trials. Karyopharm and the FDA agreed, as part of the accelerated approval agreement, to use a phase Ib trial, set to begin before 2020 ends, as a confirmatory study to assess the effect of selinexor or placebo added to a standard backbone immunochemotherapy of rituximab-gemcitabine-dexamethasone-platinum in patients with one to three prior DLBCL treatments.
The accelerated approval was based on a multicenter, single-arm phase IIb trial, SADAL (Selinexor Against Diffuse Aggressive Lymphoma), which hits its primary endpoint of overall response rate (ORR), with an ORR of 29%, including 18 (13%) complete responses and 21 (16%) partial responses.
The trial’s key secondary endpoints included a median duration of response in responding patients, 56% of whom maintained a response at three months, 38% at six months and 15% at 12 months.
The study of 134 patients, who had a median of two prior systemic therapies with a range of one to five, received a fixed 60-mg dose of Xpovio orally twice weekly on a four-week cycle. The study also included patients with germinal center B-cell (GCB) or non-GCB subtypes of DLBCL.
Xpovio blocks the nuclear export of tumor suppressor, growth regulatory and anti-inflammatory proteins, leading to their accumulation in the nucleus and enhancing cells’ anticancer activity.
The Newton, Mass.-based company’s stock (NASDAQ:KPTI) languished somewhat after the approval’s announcement, dropping about 2% in late trading June 22 before closing at $18.99 for a loss of 1 cent.