FDA clears Karyopharm’s myeloma drug despite advisory panel rejection

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The FDA has taken the unusual step of over-ruling its own advisory committee and approving Karyopharm’s Xpovio as a last-line therapy for multiple myeloma.

In February, the US regulator’s Oncologic Drugs Advisory Committee (ODAC) said that approval of Xpovio (selinexor) should be delayed until the results of a phase 3 trial are available, because of toxicity concerns.

The agency has nevertheless decided to grant a conditional approval to Xpovio (selinexor) – a first-in-class nuclear export XPO1 inhibitor – for patients with myeloma whose disease is refractory to at least two proteasome inhibitors, two immunomodulators, and anti-CD38 antibody drugs such as Johnson & Johnson’s Darzalex (daratumumab).

Karyopharm filed additional data to the FDA in the wake of the advisory committee decision, which poleaxed the company’s share price, and negotiated an extension on the agency’s review in order to file an amendment to its application.

It seems that amendment was enough to convince the FDA should be approved as an option for patients who have run out of other treatment options, and shares in Karyopharm soared more than 36% in the wake of that decision.

The approval is based on a single-arm phase 2b trial – called STORM – which showed a 25% response rate with Xpovio plus dexamethasone and a median duration of response of a little over four months. The study also revealed safety issues, including severe bleeding and infections that in some cases were linked to patient fatalities.

Xpovio staying on the market is contingent on the results of a confirmatory trial, the phase 3 BOSTON study, which is testing the drug as an add-on to Takeda’s Velcade (bortezomib) and low-dose dexamethasone in patients with myeloma who have previously received one to three prior treatment regimens.

Top-line data from BOSTON are expected by the end of this year at the earliest, or in early 2020, depending on how long patients stay alive without the disease spreading.

Karyopharm has said it intends to launch the drug in the US in the next seven days, adding that it has set a list-price of $22,000 per month for all four dosing packages, according to a Reuters report. Xpovio is also under regulatory review in Europe.