FDA Approval Sought for Selinexor in Previously Treated Multiple Myeloma

A supplement New Drug Application (sNDA) was submitted to the FDA for selinexor (Xpovio) as a treatment of patients with multiple myeloma following at least 1 prior line of therapy, Karyopharm Therapeutics, Inc announced in a press release.¹

The sNDA is supported by results from the phase 3 BOSTON study (NCT03110562) which met its primary end point after progression-free survival (PFS) was improved with once-weekly selinexor in combination with bortezomib and dexamethasone (SVd) compared with bortezomib and dexamethasone alone (Vd), according to top-line data announced in April 2020.²

“In the BOSTON study, the SVd arm demonstrated a statistically significant reduction in the risk of disease progression or death, along with a 47% increase in median progression-free survival, as well as a significantly higher overall response rate, as compared to the standard Velcade and dexamethasone (Vd) regimen. If approved, we believe XPOVIO could become an important addition to the treatment paradigm for patients with relapsed or refractory multiple myeloma, and we look forward to working with the FDA during the review process, said Sharon Shacham, PhD, MBA, founder, president and chief scientific officer of Karyopharm.¹

According to the abstract for the upcoming 2020 American Society of Oncology (ASCO) Virtual Annual Meeting, where the full results from the BOSTON study will be presented, the median PFS was 13.93 months with SVd versus 9.46 months with Vd (HR, 0.70, P =.0066). The addition of selinexor also led to an overall response rate (ORR) of 76.4% compared with 62.3% in the Vd arm (P =.0012). The median overall survival (OS) was not reached with SVd and was 25 months with Vd (P =.28).³

A significant reduction in the rate of grade ≥2 peripheral neuropathy (PN) was observed with SVd (21.0%) compared with Vd (34.3%; P =.0013), resulting in fewer deaths, and this different was clinically significant. The most commonly seen treatment-related adverse events (TRAEs) in the SVd arm versus the Vd arm were thrombocytopenia (35.9% vs. 15.2%), fatigue (11.3% vs. 0.5%) and nausea (7.7% vs. 0%), which were grade 3 or higher.

In the global randomized BOSTON study, patients receive selinexor at 100 mg, bortezomib at 1.3mg/m2, and dexamethasone at 20 mg doses. The secondary end points of the study include ORR, OS, and PN rates.

Patients with histologically confirmed multiple myeloma who had at least 1 prior anti-multiple myeloma therapy, documented evidence of progressive disease, prior treatment with bortezomib, or another proteasome inhibitor are eligible to enroll in the BOSTON study. These patients must be at least 18 years of age with an ECOG performance status of 0 to 2, as well as adequate hepatic, renal, and hematopoietic function.

The BOSTON study will be presented in an oral session at ASCO by Meletios A. Dimopoulos, MD of the National and Kapodistrian University of Athens School of Medicine in Athens, Greece.

Selinexor has a prior FDA approval in multiple myeloma in combination with dexamethasone for the treatment of adult patients with relapsed refractory disease who have received at least 4 prior therapies and whose disease is refractory to at least 2 proteasome inhibitors, at least 2 immunomodulatory agents, and an anti-CD38 monoclonal antibody. The agent is also under consideration for FDA approval as treatment of patients with relapsed or refractory diffuse large B-cell lymphoma, the sNDA for this indication was granted Priority Review and given and Prescription Drug User Fee Act target action date of June 23, 2020.¹

_References:

_{1. Karyopharm submits supplemental New Drug Application to FDA for Xpovio (selinexor) as a treatment for patients with multiple myeloma after at least one prior line of therapy [news release]. Newton, Massachusetts: Karyopharm Therapeutics, Inc; May 20, 2020. https://bit.ly/2TpjPmR. Accessed May 20, 2020.}

_{2. Karyopharm announces data from phase 3 boston study selected for late-breaking oral presentation at the american society of clinical oncology 2020 virtual scientific program [news release]. Newton, Massachusetts: Karyopharm Therapeutics, Inc; April 29, 2020. https://bit.ly/3e1r24v. Accessed May 20, 2020.}

_{3. Dimopoulos MA, Delimpasi S, Simonova M, et al. Weekly selinexor, bortezomib, and dexamethasone (SVd) versus twice weekly bortezomib and dexamethasone (Vd) in patients with multiple myeloma (MM) after one to three prior therapies: Initial results of the phase III BOSTON study. J Clin Oncol. 2020. 38: (suppl; abstr 8501). doi: 10.1200/JCO.2020.38.15_suppl.8501.}