Xpovio Conditionally Approved in China for Heavily Treated Patients
China’s National Medical Products Administration (NMPA) has conditionally approved a combination of Xpovio (selinexor) and the corticosteroid dexamethasone to treat adults with relapsed or refractory multiple myeloma (RRMM) who received at least three prior therapies.
This includes patients whose disease failed to respond to at least one immunomodulatory agent (IMiD), one proteasome inhibitor (PI), and one CD38 inhibitor and who showed disease progression on their last therapy.
“I am pleased that XPOVIO is Antengene’s first product to be approved in China and the first and only XPO1 inhibitor on the market in China,” Jay Mei, MD, PhD, chairman and CEO of Antengene, said in a press release.
Under a collaboration with Karyopharm Therapeutics, the therapy’s developer, Antengene owns the rights to develop and commercialize Xpovio in China and certain Asia Pacific countries, such as Australia, Macau, South Korea, and Taiwan.
“The approval of XPOVIO in China offers patients with relapsed multiple myeloma a new therapeutic option and the first in a new class of therapeutics, to improve outcomes for patients,” Richard Paulson, Karyopharm’s president and CEO, said in another press release.
NMPA’s conditional approval was based on data from two open-label Phase 2 trials — the global STORM study (NCT02336815) and the Chinese-based MARCH trial (NCT03944057) — where about a quarter of patients responded to the combination.
A conditional approval is granted to a medication whose immediate availability fulfills an unmet medical need when its preliminary benefits are found to outweigh its potential risks. The combo’s full approval will depend on further verification of its clinical benefits in the confirmatory BENCH Phase 3 clinical trial (NCT04939142).
The ongoing BENCH study is assessing whether adding Xpovio to the standard Velcade (bortezomib) plus low-dose dexamethasone combo delays disease progression and death in up to 150 adults with RRMM who received one to three previous lines of therapy.
Xpovio plus dexamethasone is also conditionally approved in the U.S. and in Europe — where it is sold as Nexpovio — for adults with relapsed or refractory multiple myeloma who received at least four prior therapies and failed to respond to at least two PIs, two IMiDs, and a CD38 inhibitor.
In these regions, the ongoing Phase 3 BOSTON trial (NCT03110562), with a similar design to BENCH, is serving as a confirmatory study for full approval.
In August, the combination was also approved in South Korea for the same indication as in the U.S. and Europe, and Antengene also filed several Xpovio applications with health authorities in Australia, Hong Kong, Singapore, and Taiwan.
Xpovio “has been widely adopted into practice guidelines by major oncology networks” in China, the U.S., and the European Union, Mei said, adding that “these are very positive steps to enabling product acceptance and adoption.”
“We remain committed to expanding access to selinexor across the globe with each additional ex-US approval of selinexor and look forward to working closely with Antengene to bring XPOVIO to patients in China,” Paulson added.
Xpovio is a first-in-class oral suppressor of XPO1, a protein overly produced by cancer cells to escape the action of tumor suppressor proteins. XPO1 works by exporting proteins, including tumor suppressor proteins, out of the cell nucleus, where they exert their action.
By preventing the exit of tumor suppressors from the cell nucleus, the therapy leads to the death of cancer cells while leaving healthy cells unharmed.
The STORM and MARCH studies evaluated the safety and effectiveness of Xpovio plus low-dose dexamethasone in RRMM patients. Treatment was given twice per week until disease progression, death, or unacceptable toxicity.
Part 2 of the open-label STORM recruited 83 multiple myeloma patients who failed to respond to two PIs, Velcade and Kyprolis (carfilzomib); two IMiDs, Revlimid (lenalidomide) and Pomalyst (pomalidomide); and the CD38 inhibitor Darzalex (daratumumab).
Results from this subgroup of patients showed that 25.3% responded to the Xpovio-dexamethasone combination, with a median duration of response of 3.8 months.
Patients’ median overall survival was 8.6 months, but survival nearly doubled (to a median of 15.6 months) among those who achieved at least a minimal response to treatment.
The most frequently reported adverse events included low counts of platelets, white blood cells, and red blood cells. Other common side effects were fatigue, nausea, vomiting, diarrhea, decreased appetite, weight loss, constipation, upper respiratory tract infections, and low blood sodium levels.
The Antengene-sponsored MARCH study was designed to test the combination therapy in about 82 Chinese adults with multiple myeloma who failed to respond to Velcade and Revlimid.
Results from a planned analysis of the first 60 treated participants with a median follow-up of 9.5 months showed that 26.7% responded to treatment.
Greater response rates were observed among patients who were previously treated with IMiDs, PIs, and CD38 inhibitors (33.3%) and among those who received prior CAR T-cell therapies (44.4%). The therapy also had a manageable safety profile.
“Antengene would like to thank all of the patients and investigators involved in the [clinical trials] and the NMPA for their support during the priority review,” said Kevin Lynch, MD, Antengene’s chief medical officer. “Together, we are aiming to improve the care and lives of people with cancer in China and around the world.”