Analysts question Karyopharm's PhIII endometrial cancer data as biotech will charge ahead to FDA
Karyopharm Therapeutics touted on Tuesday Phase III data for a cancer program it described as positive, but which Wall Street viewed in a more negative light.
The biotech reported topline results for Xpovio’s pivotal study in endometrial cancer, saying the drug reduced the risk of disease progression or death by 30% compared to placebo. Karyopharm noted the primary endpoint of median progression-free survival came in at 5.7 months for the active arm and 3.8 months in placebo.
But while the data were technically statistically significant, the p-value came in just under the 0.05 threshold typically used to determine such matters at p=0.0486. Karyopharm also released no additional data on overall survival, appearing to confuse analysts on the company’s fourth-quarter earnings call Tuesday morning.
As a result, Karyopharm shares were down about 21% in early Tuesday trading.
Company execs faced several questions during the call asking to clarify some of the data points. Analysts sought more answers on the specific number of survival events and discontinuation rates in each arm of the study, whether the reported data involved the “intent-to-treat” population and if the FDA agrees with PFS as an approvable endpoint.
They also seemed befuddled by Karyopharm’s decision to report data from a pre-specified subgroup despite the lingering concerns over the press release data. On the call, Karyopharm noted that while most of the answers would be provided at an upcoming medical conference, all of Tuesday’s data came from the ITT group and that regulators view PFS as the primary.
The subgroup in question dealt with 103 patients who have “wild-type p53.” Karyopharm reported that in these patients who received Xpovio, the reduction in the risk of disease progression or death was 62% compared to placebo, good for a p-value of p=0.0006. Median PFS in this group was 13.7 months against 3.7 months in the control group.
Despite the analysts’ questions, Karyopharm plans for an sNDA submission in the first half of this year, and provided the same timeline for the medical conference reveal. The biotech is going for the front-line maintenance setting in endometrial cancer.
Tuesday is not the first time Xpovio has faced controversy. When Karyopharm was initially seeking approval for relapsed or refractory multiple myeloma a few years ago, the FDA appeared skeptical of both its safety and efficacy, and an adcomm recommended regulators reject it in February 2019. But that July, the drug won accelerated approval in the indication.
Phase III results reported in March 2020 confirmed Xpovio’s clinical benefit in such patients, and the drug has since been OK’ed in late-line diffuse large B-cell lymphoma and an earlier-line multiple myeloma setting. Karyopharm is continuing to research the drug in these cancers and myelofibrosis, both as a monotherapy and in combination with other agents.
