FDA Approves Xpovio For Patients with Relapsed or Refractory DLBCL

The Food and Drug Administration (FDA) granted an accelerated approval to the oral Selective Inhibitor of Nuclear Export (SINE) compound Xpovio for the treatment of adult patients with relapsed or refractory diffuse B-cell lymphoma (DLBCL) who have received two or more prior therapies.

The accelerated approval, a program under the FDA that allows for expedited approvals of drugs that fill an unmet need, was granted based off results from the phase 2b SADL trial. In a trial of 134 patients, researchers found the agent had a 29% overall response (ORR), an 13% complete response (CR) and a median duration of response to the treatment of over 9 months. The trial’s primary endpoint was ORR.

“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 Dr. John P. Leonard, 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, in a press release.

“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.”

Patients in the trial were given 60 milligram (mg) doses of Xpovio twice a week for a four-week cycle. The trial also looked at safety for all enrolled patients, finding that the most common side effect was cytopenia (a reduction in the number of mature blood cells), gastrointestinal issues and constitutional issues, which were reversible and manageable following standard supportive care and dose reduction. The most common side effects were fatigue (63%), nausea (57%), decreased appetite (37%) and diarrhea (37%). Grade 3 and 4 side effects in more than 15% of patients included thrombocytopenia, lymphopenia, neutropenia, anemia and hyponatremia.

“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 Dr. Sharon Shacham, Founder, President and Chief Scientific Officer of Karyopharm, the manufacturer of the agent, in the release. “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.”

Further approval of Xpovio in patients with DLBCL is contingent on additional confirmatory trials of the current data, however, Karyophram officials are looking to expand Xpovio into the larger DLBCL patient population.

Check back later for what you need to know about this approval.