Karyopharm's Oral Therapy Xpovio (Selinexor) Achieves Primary Endpoint in Phase 3 BOSTON Trial for Relapsed/Refractory Multiple Myeloma

On March 3, Karyopharm Therapeutics announced that Xpovio (selinexor), in combination with Velcade (bortezomib) and dexamethasone, met the primary endpoint in the Phase 3 BOSTON clinical trial for patients with relapsed/refractory multiple myeloma who had received one to three prior therapies. Compared with patients receiving only Velcade and dexamethasone, the triplet regimen containing Xpovio significantly reduced the risk of disease progression or death.

Last February, the FDA Advisory Committee voted 8–5 against supporting the accelerated approval of this drug, casting a shadow over its potential approval. Subsequently, the FDA announced a three-month extension of the review process, and Karyopharm submitted updated data from a Phase 3 clinical trial to the agency. Finally, last July, the FDA announced the accelerated approval of the drug, stating in the approval press release that the efficacy assessment of Xpovio had incorporated the most recently submitted clinical study information. The positive results from the BOSTON trial announced today are believed to further confirm the drug’s efficacy.

Multiple myeloma is a blood cancer caused by the malignant transformation of plasma cells in the bone marrow. Abnormal plasma cells accumulate in the bone marrow, forming tumors in multiple bones throughout the body. These cells not only fail to perform their normal functions but also impair the bone marrow’s ability to produce healthy blood cells. Although various therapies are currently available for multiple myeloma, many patients still develop resistance to all approved treatments, creating an urgent need for novel therapies with innovative mechanisms to control tumor growth.

Xpovio, developed by Karyopharm Therapeutics, is an oral selective inhibitor of nuclear export (SINE) that binds to the nuclear export protein XPO1 and inhibits its function, leading to the accumulation of tumor suppressor proteins in the nucleus. This accumulation reactivates or enhances their tumor-suppressive functions, thereby inducing specific apoptosis in tumor cells while causing no significant adverse effects on normal cells.

▲Xpovio Met Primary Endpoint in the BOSTON Study (Image source: Reference [2])

The Phase 3 clinical study named BOSTON is a randomized, multicenter, active-controlled trial involving 402 patients with multiple myeloma who had received one to three prior lines of therapy. The trial results demonstrated that, compared to the active control group receiving Velcade and dexamethasone combination therapy, the addition of Xpovio significantly reduced the risk of disease progression or death. The median progression-free survival (PFS) for patients in the treatment group and the active control group was 13.93 months and 9.46 months, respectively, representing a difference of 4.47 months. Detailed data from this trial will be presented at medical conferences in the second quarter of this year.

“The BOSTON study is the first Phase 3 clinical trial to demonstrate that combining Xpovio with current standard-of-care therapies can achieve clinically and statistically significant responses in patients with previously treated multiple myeloma,” said Dr. Sharon Shacham, President and Chief Scientific Officer of Karyopharm. “In this study, the addition of Xpovio to the combination regimen extended progression-free survival (PFS) by 47%. We believe this represents a major advance in the treatment of patients with relapsed or refractory multiple myeloma.”

References:

[1] Karyopharm Announces Phase 3 BOSTON Study Meets Primary Endpoint with Significant Increase in Progression-Free Survival in Patients with Multiple Myeloma Following One to Three Prior Lines of Therapy, Retrieved March 02, 2020, from https://investors.karyopharm.com/news-releases/news-release-details/karyopharm-announces-phase-3-boston-study-meets-primary-endpoint

[2] Phase 3 BOSTON Study Top-line Results Conference Call, Retrieved March 02, 2020, from https://investors.karyopharm.com/static-files/c2c73818-607a-4b7d-912b-a05a6b6adaa7

Flash | PFS Extended by 47% in Patients with Refractory Multiple Myeloma; Novel Oral Therapy Meets Phase 3 Clinical Endpoint

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