After Karyopharm submitted Phase III data from its SIENDO study on Selinexor, the FDA said that it is unlikely to support an sNDA approval for the drug.
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Karyopharm Therapeutics, Inc., a Massachusetts-based pharmaceutical company that develops novel cancer therapies, announced an update on its drug Selinexor. After Karyopharm submitted Phase III data from its SIENDO study on Selinexor, the U.S. Food and Drug Administration said that it was unlikely to support an sNDA (supplemental New Drug Application) approval for the drug.
The Phase III SIENDO study is a multi-center, placebo-controlled, randomized study evaluating Selinexor as a treatment for advanced or recurrent endometrial cancer. Endometriosis, which is the lining of the uterus, is the most common type of reproductive organ tissue to house cancer in women, according to the American Cancer Society. About 65,950 new cases of uterine cancer are diagnosed each year.
In the SIENDO study, Karyopharm enrolled 263 patients with primary Stage IV or recurrent endometrial cancer who had had either a partial or complete response after 12 weeks of treatment with standard taxane-platinum combination chemotherapy. Patients received either 80 mg of Selinexor or placebo weekly to see if Selinexor would help prevent cancer from progressing.
When Karyopharm first announced the results of the SIENDO study in February 2022, the data looked promising. Karyopharm said that its Selinexor drug demonstrated “significant 50% improvement in median progression-free survival compared to placebo.” One group, in particular, had especially hopeful results. Patients in the study with a genome called p53 wild-type experienced even more benefit—they had a progression-free survival rate of 13.7 months, compared to the average of 5.7 months for other patients treated with Selinexor and only 3.8 months for patients on a placebo.
Additionally, the Phase III study said that Selinexor was well tolerated and had a low discontinuation rate due to adverse events - around 10.5%.
Based on those results, Karyopharm said it planned to apply for an FDA sNDA. But after reviewing the data, the FDA had “differing views” on how significant the study was. The regulator also doubted the overall clinical benefit for the endometrial cancer population base.
After a “productive meeting” with the FDA, Karyopharm stated the drug’s next steps would be to undergo further studies in patients with advanced or recurrent endometrial cancer who also had the p53 wild-type genome.
“We strongly believe in Selinexor’s potential in patients with p53 wild-type and are excited to further evaluate it in this patient population to better understand its potential to address the unmet need in women with endometrial cancer,” said Sharon Shacham, Karyopharm’s chief scientific officer.
As Karyopharm continues to collect and analyze data from the SIENDO study, it will work with the FDA to organize a new placebo-controlled, randomized clinical study of Selinexor involving patients with p53 wild-type this year. To get the clinical trial started quickly, the company is working with the FDA, the European Network of Gynaecological Oncological Trial groups, and the Gynecologic Oncology Group Foundation. Karyopharm expects to start the new study this year and have data available by mid-2024.
This decision from the FDA is tough news for Karyopharm. The company is supposed to present the SIENDO study data at two upcoming conferences: the European Society of Medical Oncology’s Virtual Plenary on March 17, and the Society for Gynecologic Oncology 2022 Annual Meeting on Women’s Cancer from March 18-21. The FDA’s update lessens the excitement from the data Karyopharm has to share.
This news follows several other recent announcements from Karyopharm, including major changes to its clinical leadership team.
Karyopharm remains optimistic about Selinexor.
“Selinexor has the potential to transform the way advanced or recurrent endometrial cancer is treated in patients with p53 wild-type and I look forward to learning more from a new study,” said Professor Ignace Vergote, principal investigator of the SIENDO study and a gynecological oncologist.
