Karyopharm AML drug fails phase 2, giving stock whiplash

A phase 2 trial of Karyopharm’s selinexor in patients with acute myeloid leukemia (AML) has been deemed destined to fail during an interim analysis. The failure wiped 15% of Karyopharm’s stock price after hours, eradicating most of the gains it made earlier in the day.

Karyopharm enrolled 176 patients with relapsed of refractory AML aged 60 years and older and gave them either its oral inhibitor of the nuclear export protein XPO1 or one of four physician's choice therapies, including regimens incorporating Celgene’s Vidaza and Otsuka’s Dacogen. The trial set out to show whether selinexor improved overall survival—and on that front the study fell short.

Together with an independent committee, Karyopharm has concluded the selinexor cohort will not achieve a statistically-significant improvement in overall survival. But, rather than halting the study, Karyopharm is allowing patients to continue with treatment after talking to their physicians. The decision to continue the trial is underpinned by safety and efficacy data.

In the selinexor cohort, 13% of patients experienced complete responses, compared to 3% in the control arm. And, according to Karyopharm, these responders “showed a substantial OS benefit as compared with the physician’s choice arm.” When paired to an acceptable safety profile, those data were sufficiently encouraging to prompt Karyopharm to allow the trial to continue. The firm is also looking to investigator-sponsored trials to test how selinexor works in combinations in AML.

While those activities mean selinexor is down but not out in older AML patients, the phase 2 data nonetheless shift the focus at Karyopharm to other indications, some of which were always seen as better bets.

For anyone who viewed AML as a long shot, the phase 2 data contain some reasons for optimism. Notably, the phase 2 data downplay worries about the link between selinexor and sepsis that surfaced in 2015. The rate of sepsis in the selinexor arm was 4.9%, around one percentage point lower than in the control cohort. The trial also associated selinexor with fewer cases of febrile neutropenia.

Those findings provided succour to believers in the potential for selinexor to succeed, particularly in multiple myeloma.

“The monotherapy signals do indicate the drug is active, and given the accumulating clinical and preclinical data showing selinexor synergy in a range of combination therapies, we remain positive on the drug’s potential, particularly in MM in combination with Velcade,” Jefferies Analyst Brian Abrahams, M.D. wrote in a note to investors. “We do not see any negative read-throughs to MM or other indications and remain positive on the potential for selinexor crossing the goal line as a treatment for later-line MM [patients.]”

Investors’ knee-jerk reactions were less charitable. Karyopharm’s share price fell 15% after hours, wiping out most of the gains it made during a 25% surge earlier in the day.