A company developing a new class of drugs for multiple myeloma is aiming for the Food and Drug Administration’s green light for its lead product candidate.
Newton, Massachusetts-based Karyopharm Therapeutics said Wednesday that it had starting a rolling New Drug Application submission to the FDA for the drug, selinexor. The drug is known as a selective inhibitor of nuclear export, or SINE, which works by causing tumor-suppressing proteins to accumulate in cell nuclei by binding to an inhibiting a protein called XPO1. The company expects to complete the submission in the second half of this year. The drug has FDA fast-track designation for penta-refractory disease, a setting that is regarded as an unmet but growing need due to patients living longer with multiple myeloma, which is considered an incurable disease.
The company is seeking accelerated approval for patients with so-called penta-refractory disease. Penta-refractory means that they have failed on five key drugs used to treat multiple myeloma, including two proteasome inhibitors, two immunomodulatory drugs and a monoclonal antibody targeting the antigen CD38, along with an alkylating agent and glucocorticoids. Approved proteasome inhibitors include Takeda Pharmaceutical Co.’s Velcade (bortezomib) and Ninlaro (ixazomib), as well as Amgen’s Kyprolis (carfilzomib). Celgene makes all three the myeloma-indicated immunomodulators, namely Thalomid (thalidomide), Revlimid (lenalidomide) and Pomalyst (pomalidomide). The only FDA-approved CD38-targeting antibody is Johnson & Johnson’s Darzalex (daratumumab).
The submission is based on results of the Phase IIb STORM study that the company announced in April. Among the 122 penta-refractory patients enrolled in the study, 25.4 percent responded to therapy, including two patients who achieved complete responses and 29 who achieved partial responses or very good partial responses, with a median duration of response of 4.4 months.
Other investigational therapies have also shown efficacy in the penta-refractory setting. In June, Cambridge, Massachusetts-based bluebird bio announced data at the American Society of Clinical Oncology meeting from its Phase I clinical trial of bb2121, a CAR-T therapy that targets the BCMA antigen. The study showed an overall response rate of 95.5 percent in the 22-patient dose-expansion cohort, including a 50 percent complete remission rate. Moreover, more than 90 percent of patients were penta-refractory and had received an autologous stem cell transplant. The CAR-T is being developed under a partnership between bluebird and Celgene.
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