EMA committee recommends approval of Karyopharm & Menarinis Nexpovioto treat patients with refractory multiple myeloma

Karyopharm Therapeutics Inc., a commercial-stage pharmaceutical company pioneering novel cancer therapies, and the Menarini Group (Menarini), a privately-held, leading international pharmaceutical company, announced that the European Medicines Agency's (EMA) Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion recommending approval of Nexpovio (selinexor), a first-in-class, oral exportin 1 (XPO1) inhibitor, in combination with once weekly bortezomib (Velcade) and low-dose dexamethasone (SVd) for the treatment of adults with multiple myeloma who have received one to three prior lines of therapy. The positive CHMP opinion is a scientific recommendation for marketing authorization and one of the final steps before the European Commission (EC) makes a decision on Karyopharm's Nexpovio application. The EC's decision is expected within approximately 60 days following the CHMP recommendation. In December 2021, Karyopharm and Menarini Group entered into an exclusive license agreement to commercialize Nexpovio (selinexor) in Europe. "Despite therapeutic advances, multiple myeloma remains an incurable disease that is difficult to treat," said Richard Paulson, president and chief executive officer of Karyopharm. "Today's positive CHMP opinion brings us one step closer to our goal of making Nexpovio available to patients globally who may benefit from its novel mechanism of action. We are pleased to have Menarini as a partner in this effort given its commercialization expertise as well as strong heritage and footprint in Europe." "We are thrilled with the CHMP's recommendation in favour of Nexpovio and what it represents for multiple myeloma patients in need of new and innovative treatment options," said Elcin Barker Ergun, chief executive officer of Menarini. "Pending potential marketing authorization from the EC, we will work closely with appropriate authorities to ensure this important treatment can be made available to patients in Europe." Karyopharm's application is supported by data from the phase 3 BOSTON study, which evaluated the SVd triplet regimen in patients with relapsed or refractory multiple myeloma and were published in The Lancet (Grosicki, et al.) in November 2020. This CHMP opinion follows the approval of Xpovio (selinexor) by the US Food and Drug Administration in December 2020 in the SVd combination in patients with multiple myeloma after at least one prior therapy. The Phase 3 BOSTON (Bortezomib, Selinexor and Dexamethasone) study was an multi-center, randomized study (NCT03110562), which evaluated 402 adult patients with relapsed or refractory multiple myeloma who had received one to three prior lines of therapy. The study was designed to compare the efficacy, safety and certain health-related quality of life parameters of once-weekly SVd versus twice-weekly bortezomib and low-dose dexamethasone (Vd). The primary endpoint of the study was progression-free survival (PFS) and key secondary endpoints included overall response rate (ORR), rate of peripheral neuropathy, and others. Additionally, the BOSTON study allowed for patients on the Vd control arm to crossover to the SVd arm following objective (quantitative) progression of disease verified by an Independent Review Committee (IRC). The BOSTON study was conducted at over 150 clinical sites internationally. Despite the study having a high proportion of patients with high-risk cytogenetics (~50%) compared to other Velcade-based studies in previously treated myeloma, the median PFS in the SVd arm was 13.93 months compared to 9.46 months in the Vd arm, representing a 4.47 month (47%) increase in median PFS (hazard ratio (HR)=0.70; p=0.0075). The SVd arm also demonstrated a significantly greater ORR compared to the Vd arm (76.4% vs. 62.3%, p=0.0012). Patients who had received only one prior line of therapy also demonstrated a higher ORR on the SVd arm as compared to the Vd arm (80.8% vs. 65.7%, p=0.0082). Importantly, SVd therapy compared to Vd therapy showed consistent PFS benefit and higher ORR across several important subgroups. Multiple myeloma is an incurable cancer with significant morbidity and the second most common hematologic malignancy. According to the World Health Organization, in 2020, there were approximately 51,000 new cases and 32,000 deaths from multiple myeloma in Europe1. While the treatment of multiple myeloma has improved over the last 20 years, and overall survival has increased considerably, the disease remains incurable, and nearly all patients will eventually relapse and develop disease that is refractory to all approved anti-myeloma therapies. Therefore, there continues to be a high unmet medical need for new therapies, particularly those with novel mechanisms of action. Nexpovio, which is marketed as Xpovio in the US, is a first-in-class, oral exportin 1 (XPO1) inhibitor. Nexpovio functions by selectively binding to and inhibiting the nuclear export protein exportin 1 (XPO1, also called CRM1). Nexpovio blocks the nuclear export of tumor suppressor, growth regulatory and anti-inflammatory proteins, leading to accumulation of these proteins in the nucleus and enhancing their anti-cancer activity in the cell. The forced nuclear retention of these proteins can counteract a multitude of the oncogenic pathways that, unchecked, allow cancer cells with severe DNA damage to continue to grow and divide in an unrestrained fashion. Nexpovio has been granted conditional marketing authorization by the European Commission in combination with dexamethasone for the treatment of multiple myeloma in adult patients who have received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors, two immunomodulatory agents, and an anti-CD38 monoclonal antibody, and who have demonstrated disease progression on the last therapy. Therapeutic indication for Nexpovio in the EU Member States as well as Iceland, Liechtenstein, Norway and Northern Ireland. Nexpovio is also approved in the UK under a Conditional Marketing Authorisation. Nexpovio is indicated in combination with dexamethasone for the treatment of multiple myeloma in adult patients who have received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors, two immunomodulatory agents and an anti-CD38 monoclonal antibody, and who have demonstrated disease progression on the last therapy.

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