Xpovio Triple Combo Before FDA for Previously Treated Myeloma Patients

Karyopharm Therapeutics is asking that Xpovio (selinexor) be approved with Velcade (bortezomib) and low-dose dexamethasone to treat people with multiple myeloma after at least one line of therapy.

The request was submitted to the U.S. Food and Drug Administration (FDA) in the form of a supplemental new drug application (sNDA).

It is based on new data from the BOSTON Phase 3 trial (NCT03110562) recently presented at the 2020 American Society of Clinical Oncology (ASCO) Virtual Scientific Program.

The company is now preparing a similar request, called a marketing authorization application, for the European Medicines Agency.

“The sNDA requesting approval for Xpovio as a new, second line treatment for patients with multiple myeloma has now been submitted to the FDA and we look forward to working closely with regulatory authorities to make this potential new treatment option available to the oncology community as quickly as possible,” Sharon Shacham, PhD, MBA, president and chief scientific officer of Karyopharm, said in a press release.

Xpovio, developed by Karyopharm, is a first-in-class oral inhibitor of the XPO1 protein. It works by preventing tumor suppressor proteins from exiting the cell nucleus, resulting in cancer cell death.

The FDA gave accelerated approval to Xpovio, in combination with dexamethasone, last year to treat certain adults with relapsed or refractory multiple myeloma. These patients had to have tried at least four prior therapies, and also fail to respond to other forms of treatment, including at least two proteasome inhibitors, two immunomodulatory agents, and an anti-CD38 monoclonal antibody.

Now the company is seeking Xpovio’s approval, when given alongside Velcade and low-dose dexamethasone, for the treatment of those with multiple myeloma who had at least one line of therapy.

BOSTON was a Phase 3 trial assessing the safety and efficacy of a Xpovio, Velcade, and low-dose dexamethasone combination — compared with Velcade and low-dose dexamethasone alone — in adults with relapsed or refractory multiple myeloma.

It enrolled 402 patients with one to three prior lines of therapy. All were randomly assigned to the triple combination or to standard Velcade plus dexamethasone.

Triple combination patients received Xpovio and Velcade once a week, along with 40 mg of dexamethasone weekly. Standard treatment patients were a control group, and given Velcade twice weekly plus 80 mg of dexamethasone each week.

The study’s main goal was the treatment’s ability to extend the time patients lived without showing signs of disease worsening or dying from any cause, a measure known as progression-free survival (PFS).

Secondary goals included the percentage of patients responding to treatment, the effects of treatment on participants’ overall survival, and safety assessments.

Previous findings from BOSTON, announced earlier this year, showed the study met its main goal. The Xpovio regimen prolonged the time patients lived without signs of disease progression by 47% compared with the standard regimen.

New data presented at ASCO showed that in addition to prolonging patients’ median PFS from 9.5 to 14 months — representing a 30% reduction in the risk of disease progression or death — Xpovio led to a higher treatment response rates compared with the control regimen (76.4% vs. 62.3%).

Improvements in PFS and treatment response rates were consistent among different patient subgroups, including those ages 65 and older, those with moderate impairments in kidney function, and those who previously failed to respond to treatment with Velcade or Revlimid (lenalidomide).

Xpovio was also linked to improvements in overall survival and lower rates of severe peripheral neuropathy compared with standard treatment (21.0% vs. 34.3%).

The most common treatment-related adverse events observed in patients on the triple therapy included low platelet counts, fatigue, and nausea.

“The clinically significant benefits demonstrated in the BOSTON study suggest that, if approved in this expanded patient population, Xpovio could become an important and more convenient addition in the treatment paradigm for patients after at least one prior line of therapy,” said Meletios Dimopoulos, MD, professor and chairman of the department of Clinical Therapeutics at the National and Kapodistrian University of Athens School of Medicine, and principal investigator of BOSTON.