Karyopharm storms into ASH with updated Phase 2b data
- Karyopharm Therapeutics presented additional data for selinexor (KTP-0330), in combination with dexamethasone, at the annual American Society of Hematology (ASH) meeting. Results from the STORM study, which tested the drug in patients with heavily pretreated refractory multiple myeloma, showed a 21% overall response rate (ORR) among the 78 participating patients.
- The response rate was the same for the 48 patients with "quad-refractory" multiple myeloma, characterized as a form of the disease resistant to bortezomib, carfilzomib, lenalidomide, and pomalidomide. In the 30 patients with "penta-refractory" disease — additionally resistant to an anti-CD38 monoclonal antibody — the ORR was 20%
- The clinical benefit rate (the ORR plus the minor response) was 32% for all patients, 29% for quad-refractory patients and 37% for penta-refractory patients. The median overall survival was 9.3 months for all patients, and a median duration of response of 5 months.
Karyopharm has expanded the study to include additional patients with penta-refractory myeloma and expects to report top-line data in early 2018.
The American Cancer Society predicts over 12,600 deaths in the US alone from multiple myeloma in 2016, and more than 30,000 new cases. The majority of patients become resistant to the standard treatments for multiple myeloma – initially "quad-refractory" to IMiDs (Revlimid [lenalidomide] and Imnovid/Pomalyst [pomalidomide]) and proteasome inhibitors (Velcade [bortezomib] and Kyprolis [carfilzomib]). Patients can then progress to becoming "penta-refractory" to anti-CD38 monoclonal antibodies (Darzalex [daratumumab] and isatuximab). This creates a population of high unmet need.
Dan T. Vogl, assistant professor at the Perelman School of Medicine, said: "The quad- and penta-refractory populations are continuing to expand as patients live longer and cycle through a variety of treatment options, including immunomodulatory drugs, proteasome inhibitors, or anti-CD38 monoclonal antibodies, before their disease ultimately becomes refractory and non-responsive."
Selinexor is an oral selective XPO1 inhibitor, so has a different mode of action to existing agents, and according to the company is the only drug with reported response rates in penta-refractory patients. At the Karyopharm-hosted event at ASH, attended by analysts from Jefferies, the panel reflected interest and enthusiasm from key opinion leaders with the mechanism of action, the data, the regulatory path, and the potential role for selinexor in multiple myeloma treatment. In the discussions at ASH, the planned BOSTON Phase 3 design, with a Velcade/dexamethasone control arm, was seen as reasonable.
"Despite many available therapies, [the physicians] felt selinexor's clear single-agent activity would enable increased confidence that it would provide additional benefit, while potentiating recycling of other meds, in combinations. Oral administration with a once or twice a week pill should also help compliance," according to a note from Jefferies.
The data from the combo pomalidomide STOMP study is also looking positive, though this is not yet as mature.
"The data presented today further support the rationale for selinexor as a promising new treatment for patients with refractory myeloma with no clearly beneficial treatment options," Karyopharm's president Sharon Shacham said in a statement released Dec. 4.
- Karyopharm Therapeutics Statement
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