Selinexor (Xpovio, Karyopharm) tablets in combination with the corticosteroid dexamethasone was approved under the agency's accelerated approval program.
Officials with the FDA today granted accelerated approval to selinexor (Xpovio, Karyopharm) tablets in combination with dexamethasone for the treatment of certain adult patients with previously-treated relapsed or refractory multiple myeloma (RRMM), according to a press release.
Selinexor is indicated for adults with RRMM who have received at least 4 prior therapies and whose disease is refractory to at least 2 proteasome inhibitors, at least 2 immunomodulatory agents, and an anti-CD38 monoclonal antibody.
There are more than 32,000 new cases of multiple myeloma each year and over 130,000 patients living the disease, according to Karyopharm. However, there is currently no cure and patients’ disease will typically progress following treatment.
Selinexor is the first FDA-approved medication for this indication. A first-in-class oral Selective Inhibitor of Nuclear Export compound, selinexor works by blocking 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 accelerated approval is based on results from the phase 2b STORM trial which evaluated selinexor in patients with RRMM who had previously received 3 or more anti-myeloma treatment regimens.
In STORM Part 2, a total of 122 patients were treated with selinexor 80 mg in combination with dexamethasone 20 mg on days 1 and 3 of every week. Of the patients in the trial, 83 had RRMM that was documented to be refractory to bortezomib, carfilzomib, lenalidomide, pomalidomide, and daratumumab.
A prespecified subgroup analysis of 83 patients whose disease was refractory to prior treatments showed that the benefit-risk ratio was greater in the more heavily pretreated population than the overall trial population. The overall response rate, which served as the basis for selinexor’s accelerated approval, was 25.3% in this subgroup, which included 1 stringent complete response, no complete responses, 4 very good partial responses, and 16 partial responses. The median time to first response for these patients was 4 weeks and the median duration of response was 3.8 months, according to the data.
The most common adverse effects reported from both STORM Parts 1 and 2 were thrombocytopenia, fatigue, nausea, anemia, decreased appetite, decreased weight, diarrhea, vomiting, hyponatremia, neutropenia, leukopenia, constipation, dyspnea, and upper respiratory tract infections.
“Despite recent advances in the treatment of multiple myeloma, almost all our patients will develop disease that is resistant to the 5 most commonly used anti-myeloma drugs we currently have available, and the prognosis for this patient population is particularly poor,” Paul Richardson, MD, clinical program leader and director of clinical research at Jerome Lipper Multiple Myeloma Center at the Dana-Farber Cancer Institute, said in a statement. “The accelerated approval of oral Xpovio marks an important advance in the treatment paradigm for patients with relapsed refractory multiple myeloma, and in my view, is an important addition to our therapeutic armamentarium.”
According to the FDA, continued approval for selinexor in this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial, which will be the ongoing phase 3 BOSTON study evaluating selinexor in combination with bortezomib and low-dose dexamethasone
Karyopharm anticipates selinexor to be available in the United States on or before July 10, 2019, according to the release.
Karyopharm Announces FDA Approval of XPOVIO (selinexor) for the Treatment of Patients with Relapsed or Refractory Multiple Myeloma [news release]. Karyopharm. https://investors.karyopharm.com/news-releases/news-release-details/karyopharm-announces-fda-approval-xpoviotm-selinexor-treatment. Accessed July 3, 2019.