Data from the ongoing Phase III study, which have not been publicly disclosed, influenced the decision to approve the drug, Xpovio, in “penta-refractory” myeloma.
The Food and Drug Administration granted accelerated approval to a drug for heavily pretreated multiple myeloma despite an expert panel recommending earlier this year that the decision be delayed over safety and other concerns.
Newton, Massachusetts-based Karyopharm Therapeutics said Wednesday that the agency had granted the approval to Xpovio (selinexor) – in combination with the steroid dexamethasone – in patients who have received at least four prior therapies. Patients must be refractory to at least two proteasome inhibitors, two immunomodulators and a CD38-directed monoclonal antibody – all drug classes that are commonly used for myeloma. Such patients are known as “penta-refractory, given their refractoriness to five key myeloma drugs, but Xpovio’s label does not specify which specific drugs those should be.
Shares of Karyopharm were up 36 percent on the Nasdaq following the news.
That stands in contrast to the market’s response in February, when the company’s shares dropped after the FDA’s Oncologic Drugs Advisory Committee (ODAC) voted 8 to 5 to recommend delaying a decision whether to approve the drug until results of the Phase III BOSTON trial became available. Consequently, the deadline for the FDA to reach a decision was pushed from April 6 to July 6. The company had pursued accelerated approval based on data from the Phase IIb STORM study, which had shown 25.3 percent of 83 patients responding to treatment.
In a press release announcing the approval, the FDA stated that the efficacy evaluation stemmed from additional information from an ongoing, randomized trial. In a conference call with investment analysts Wednesday, Karyopharm executives clarified that the data – which included safety and efficacy – came from BOSTON, but that they were from a data safety monitoring board analysis, and the company was not privy to them. The company said BOSTON – which tests Xpovio and dexamethasone in combination with bortezomib among patients who have received one to three prior myeloma drugs – will serve as the confirmatory trial.
Left untreated, penta-refractory patients can be expected to survive three to five months, said Perry Monaco, Karyopharm’s vice president of sales, during conference call. Consequently, the company does not anticipate significant barriers to payer coverage for the drug.
Issues that the ODAC’s briefing documents raised included the fact that STORM was a single arm trial, and that a majority of patients – more than 60 percent – had experienced serious side effects. Nearly 90 percent required a dose modification due to an adverse event that emerged during treatment, and more than one-quarter discontinued treatment for the same reason. The committee also raised questions about the dose selection used in the study.
Xpovio is a nuclear export inhibitor that works by binding to and inhibiting the nuclear export protein exportin 1, or XPO1, thereby blocking the export of tumor suppressor, growth-regulatory and anti-inflammatory proteins from the nucleus and enhancing cells’ anti-cancer activity. The company is also developing the drug in diffuse large B-cell lymphoma and some solid tumors.
Date: July 09, 2019