A combination of Nexpovio (selinexor) and the corticosteroid dexamethasone has been recommended for conditional approval in the European Union to treat adults with relapsed or refractory multiple myeloma who received at least four prior therapies.
This includes patients whose disease failed to respond to at least two proteasome inhibitors, two immunomodulatory agents, and a CD38 inhibitor, and who showed disease progression on their last therapy.
The recommendation was made by the Committee for Medicinal Products for Human Use (CHMP), an arm of the European Medicines Agency. The committee’s recommendations are generally accepted by the European Commission, which makes the final decisions. A decision about the Nexpovio combo is anticipated by April 2021.
“We are delighted that the CHMP has adopted a positive opinion for Nexpovio, which could lead to Karyopharm’s first regulatory approval in Europe,” Sharon Shacham, PhD, founder, president, and chief scientific officer of Karyopharm Therapeutics, the therapy’s developer, said in a press release.
“This positive opinion highlights the CHMP’s recognition of the positive clinical benefit-risk profile for oral Nexpovio and takes Karyopharm one step closer to bringing this important medicine to European patients in need of novel multiple myeloma treatment options,” she added.
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 BOSTON Phase 3 study (NCT03110562).
The ongoing BOSTON trial is assessing whether adding Nexpovio to the standard Velcade (bortezomib) plus low-dose dexamethasone combo delays disease progression in 402 adults with relapsed or refractory multiple myeloma who received one to three previous lines of therapy.
A potential conditional approval would follow a similar ruling in the U.S. for the same indication. Also, a triple combination of Nexpovio — sold as Xpovio in the U.S. — plus Velcade and low-dose dexamethasone was recently approved in the country for multiple myeloma patients who received at least one previous line of therapy.
Karyopharm plans to submit a similar regulatory filing to the European Medicines Agency by April 2021 to expand Nexpovio’s indications to include the triple combination for patients experiencing disease relapse after their first treatment.
Nexpovio 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, Nexpovio leads to the death of cancer cells, while leaving healthy cells unharmed.
The CHMP’s positive opinion was based on data from a subgroup of 83 patients participating in the STORM Phase 2b trial (NCT02336815) whose disease failed to respond to the two proteasome inhibitors Velcade and Kyprolis (carfilzomib), the two immunomodulatory agents Revlimid (lenalidomide) and Pomalyst (pomalidomide), and the CD38 inhibitor Darzalex (daratumumab).
STORM evaluated the safety and effectiveness of the Nexpovio-dexamethasone combo in relapsed or refractory multiple myeloma patients who had received at least three prior therapies. Participants received the combination therapy twice a week until disease progression, death, or unacceptable toxicity.
Results from this subgroup of heavily treated patients showed that 25.3% responded to the Nexpovio combo, and that responses lasted a median of 3.8 months. Also, median time to first response was about four weeks in these patients.
Of note, the median overall survival in the overall population was 8.6 months, but survival nearly doubled (to a median of 15.6 months) among those who attained at least a minimal response to treatment.
The most commonly reported adverse events (side effects) in the overall trial population were low counts of platelets, white blood cells, and red blood cells. Other common side effects included fatigue, nausea, vomiting, diarrhea, decreased appetite, weight loss, constipation, upper respiratory tract infections, and low blood sodium levels.
Serious side effects occurred in 58% of participants, and led to death in 9%. Treatment discontinuation due to adverse reactions was reported in 27% of patients.
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