Karyopharm's controversial Xpovio could see wider myeloma market after latest trial win

Karyopharm plans to file Xpovio for second-line multiple myeloma approval after a phase 3 clinical trial win. (Karyopharm)

Karyopharm’s Xpovio landed late in multiple myeloma treatment when it nabbed its initial FDA nod in mid-2019. Now thanks to a new clinical win, the drug looks on track to enter earlier use—and access a broader market opportunity.

After showing Xpovio worked in myeloma patients who have tried at least one prior line of therapy, Karyopharm management said the company plans to file for a label expansion in second-line setting in the second quarter.

“We believe the data will cement Xpovio’s use as a novel class of drug in earlier (2L & 3L) MM and should get investors to pay more attention to the broader potential,” Jefferies analyst Maury Raycroft wrote in an investor note. His team now projects Xpovio sales to hit $123 million in 2020, gradually ticking upward to cross the blockbuster threshold by 2025.

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Xpovio, given in tandem with Takeda’s Velcade once-weekly and corticosteroid dexamethasone (a regimen called SVd for short), significantly cut the risk of disease progression or death by 30% compared with twice-weekly Velcade plus dexamethasone (Vd) in myeloma patients who received one to three lines of therapy, Karyopharm recently said.

In the phase 3 Boston study, subjects on SVd lived a median of 13.93 months without their cancer progressing, versus 9.46 months in the Vd group, meaning patients lived 47% longer without disease worsening. 

On top of stronger efficacy, the SVd combo “should also have appeal given the use of less total drug (Vel 40% less and dex 25% less),” Raycroft said. If approved, it will be the only regimen with once-weekly Velcade, “which we believe could get traction in community settings,” he added.

RELATED: Karyopharm's Xpovio nabs myeloma nod despite checkered past. But 5th line?

The triplet group saw fewer peripheral neuropathy cases mainly because of less frequent Velcade dosing. Physicians often reduce Velcade to once per week in clinical practice due to that toxicity, even though most trials have tested it with twice-weekly dosing.

Industry watchers have had doubts about Xpovio’s toxicity profile, which previously got it an FDA independent advisory committee thumbs-down. In the phase 2 Storm trial, 74% of Xpovio takers developed low blood platelet count, and 27% dropped out because of bad reactions. Although the drug’s label doesn’t include a black box safety warning, the long list of side effects and narrow approval as a fifth-line treatments had bear investors questioning its commercial opportunity.

Compared with the Storm trial, the total Xpovio dose was also lowered in the new Boston study, from 80 mg twice a week to 100 mg per week. 

With the drug already bearing a novel mechanism of action, oral convenience and flexible potential combination options with other myeloma drugs, Xpovio’s Boston win “provides appeal for broader use and a meaningful commercial opportunity,” Raycroft said.

About 90% of the total 150 Boston trial sites had never used Xpovio before, indicating potential in the real world, Raycroft said. Some physicians who have adopted Xpovio are already using it in combos mostly with Veclade, “which may also influence regulatory views on approval and facilitate commercial uptake,” he argued.

RELATED: Amgen's Kyprolis, J&J's Darzalex team up on myeloma survival win

The myeloma market is very competitive. In the second-line setting, older Velcade is giving way to Amgen’s newer proteasome inhibitor Kyprolis. 

Karyopharm is also eyeing other myeloma combos, currently running the phase 2 Stomp trial that combines Xpovio with other drugs including Kyprolis, legacy Celgene’s standard-of-care Revlimid and Johnson & Johnson’s Darzalex, Raycroft noted. It’s also expecting an FDA decision for Xpovio in relapsed/refractory diffuse large B-cell lymphoma by June 23.

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