Even in its final hours selinexor’s wild ride to US approval could not avoid drama. Yesterday’s thumbs up was preceded by the accidental internet posting of full prescribing information and a Youtube video claiming that the drug was approved, though it was hours before the FDA actually announced this.
Selinexor’s originator, Karyopharm, shot up 36% before being halted, presumably as its IR department rushed to prepare a statement. The fact that the drug has sidestepped toxicity worries is clearly positive, though the biggest question remains whether it can make headway in early lines of multiple myeloma treatment.
With the US markets closed for Independence Day today investors have some time to digest this information. Their full reaction will not become apparent until the stock exchange reopens on Friday.
Clearly on the plus side is that selinexor, now trademarked Xpovio, has secured accelerated approval largely on the basis of the phase II, late-line Storm study. This was in spite of a US adcom voting to wait until full data from Boston, a phase III trial in second to fourth-line subjects, are generated in 2020.
And Xpovio’s label looks relatively clean, with no black box warning, for instance. In Storm 74% of selinexor subjects developed thrombocytopenia, and 27% discontinued treatment; the fatal adverse event rate was 9%.
The FDA seems to have been satisfied that this level of toxicity is acceptable given the unmet need of the last-ditch setting in which Xpovio has been approved: patients must have received at least four prior therapies and be refractory to at least two proteasome inhibitors, at least two IMIDs, and an anti‐CD38 MAb.
The reality of this for Karyopharm, however, is that it amounts to a tiny market. According to EvaluatePharma’s consensus of sellside forecasts the drug will bring in $572m in 2024 revenues, and it is obvious that late-line patients alone will not generate these.
Mechanistically, selinexor is an irreversible inhibitor of a protein called XPO1, and looks to be the first selective inhibitor of nuclear export to have reach the market.
If there is a ray of hope it lies in that earlier-line Boston study. After the adcom’s vote the FDA decided to delay its action date on selinexor by three months, and some had suggested that this was to give it time to look at some of the early data from Boston, an open-label trial.
Yesterday it became apparent that this was indeed the case: while Xpovio’s label cites only the 21% overall remission rate seen in Storm, the agency’s statement says its evaluation was “supported by additional information from an ongoing, randomised trial”.
Karyopharm bulls might well extrapolate that the FDA already agreeing to consider Boston bodes well for extending Xpovio’s approval to the earlier settings in this study. Those settings are highly competitive, and toxicity will weigh heavy, but with today’s FDA you never know.
|Xpovio's multiple myeloma trials|
|Study||Setting||Trial ID||Data due|
|Storm||Dexamethasone combo, penta and quad-refractory subjects, single-arm||NCT02336815||Reported|
|Boston||On top of Velcade + dexamethasone, 2nd to 4th-line, 2-arm, open-label||NCT03110562||Mid-2020|