Antengene’s XPO1 Inhibitor Receives First-In-Class Approval in China for Multiple Myeloma

Patients with multiple myeloma, a cancer of the plasma cells, who have failed three lines of therapy can now try selinexor (brand name Xpovio), a first-in-class XPO1 inhibitor recently approved by the NMPA in China. However, drug pricing and toxicities associated with selinexor will be a sticking point for physicians prescribing the medication. 

Originally developed by Karyopharm Therapeutics, a Massachusetts, US-based pharmaceutical company, selinexor was licensed to Shanghai’s Antengene in 2018 in a deal worth around $162 million. The deal gave Antegene rights to develop and commercialize the drug in China and certain countries in the Asia Pacific region. With the NMPA nod, Antengene now has its first product ready for launch in China. 

Selinexor is an oral Selective Inhibitor of Nuclear Export (SINE) that targets the XPO1, a nuclear export protein. XPO1, found in high concentrations in cancer cells, prevents the action of tumor suppressor proteins that work to stop cancer growth. The binding of selinexor to XPO1 leads to accumulation of the anticancer proteins in the cell nucleus. This results in apoptosis, or programmed cell death, of cancer cells, while normal cells are mostly unaffected. 

Approvals in China and Beyond

The conditional approval of selinexor in China covers patients with relapsed or refractory multiple myeloma (rrMM), who have failed three lines of therapy including a proteasome inhibitor, an immunomodulatory agent and an anti-CD38 monoclonal antibody. 

Approval was based on results from the global Phase 2 Storm trial and Antengene’s Phase 2 March trial in China. 

The Storm trial showed that selinexor in combination with dexamethasone had an overall response rate of 25.3% in subgroup of 83 patients who were penta-refractory (refractory to bortezomib, carfilzomib, lenalidomide, pomalidomide, and daratumumab).

Meanwhile, the March trial, involving 82 patients, showed that 29.3% of all treated patients and 25% of those who were refractory to at least a proteasome inhibitor (such as bortezomib), an immunomodulatory agent and a anti-CD38 antibody responded to selinexor. The results were said to be in line with those from the Storm trial. 

A confirmatory Phase 3 trial conducted by Antengene in China is ongoing. Dubbed the Bench study, the trial is evaluating selinexor in combination with bortezomib and low-dose dexamethasone in patients with rrMM. Antengene is conducting a total of 10 studies of selinexor in China  (three in collaboration with Karyopharm) for other blood cancers and advanced solid tumors. 

Selinexor was first approved in the US in 2019, as part of a combination therapy with dexamethasone to treat patients with rrMM who have received at least four prior therapies. The drug added a second indication for second line multiple myeloma in 2020 and a third for relapsed or refractory diffuse large B-cell lymphoma (rrDLBCL) this June. 

In March, the drug was conditionally approved by the EU under the brand name Nexpovio, to be used together with dexamethasone to treat quad-refractory multiple myeloma patients.  

In Korea, selinexor was approved after a priority review for two indications: in combination with dexamethasone in penta-refractory rrMM, and as third-line monotherapy for rrDLBCL.   

Side Effects and Pricing 

The pricing and side effects associated with selinexor have raised concern, which may hinder its sales in China. In the Storm study, 89% of participants experienced serious drug-related events, with two patients dying from selinexor-associated toxicities, one from sepsis, another from pneumonia. Other side effects include thrombocytopenia, hyponatremia, anemia, and nausea. 

Until more data from clinical trials are available, the conditional approval for selinexor is likely to hold where they are given. The other drawback of the drug is its pricing; at nearly $22,000 per month in the US, selinexor is considerably pricey. A cost-effectiveness analysis of a weekly regime of selinexor, bortezomib and dexamethasone versus twice-weekly bortezomib and dexamethasone in rrMM has concluded that selinexor’s pricing has to be halved in order for it to be cost-effective. 

Author

Joy Lin

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