publication date: Mar. 1, 2019

ODAC gives thumbs down to single-arm trial of two-drug combination for multiple myeloma

Committee focuses on meaning of equipoise, accelerated approval, confirmatory trials

By Paul Goldberg

It’s not just the absence of a randomized trial that prompted the FDA Oncologic Drugs Advisory Committee to recommend against an accelerated approval of the Karyopharm Therapeutics Inc. drug selinexor for late-stage multiple myeloma.

When a single-arm trial produces dramatic results, an approval can be a no-brainer, as was the case with, say, CAR-T for leukemia and lymphoma.

Alas, the data on selinexor lacked the level of clarity of the CAR-T trials.

Karyopharm’s trial, called STORM, produced response rates that some ODAC members could interpret as “reasonably likely to predict” patient benefit, but in STORM, the drug was given in combination with dexamethasone, which has its own efficacy and toxicity.

What did steroids contribute to safety and efficacy of the regimen? Could dexamethasone’s contribution be teased out from that of selinexor? This may sound like a mundane regulatory question, but FDA does require the answer, and ODAC appears to have concurred that this distinction is worth establishing.

ODAC’s decision could have been easier had the regimen been well tolerated. Alas, over 88 percent of patients got dose modifications because of adverse events. Plus, safety couldn’t be evaluated more reliably because of the absence of a control arm.

On Feb. 26, after having parsed through the data and hearing 17 public witnesses who supported approval in this desperate indication, ODAC voted 8:5 against granting an accelerated approval for the regimen, recommending instead that the decision be made based on an ongoing randomized trial that is now underway … Continue reading ODAC gives thumbs down to single-arm trial of two-drug combination for multiple myeloma

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