Karyopharm’s attempt to gain an accelerated approved for selinexor as a treatment for drug-resistant cases of multiple myeloma is in serious jeopardy. And investors know it.
Given the history of the FDA with these kinds of reviews, Tuesday’s assessment will likely be harsh.
Batting back the optimistic assessment the biotech gave selinexor, the internal FDA review concludes that there’s precious little evidence that the drug has any significant value on its own. Just as bad, the drug has been tied to high rates of toxicity and a higher death rate when it was tested in a randomized controlled study for acute myeloid leukemia.
“Treatment with selinexor is associated with significant toxicity,” the review states unambiguously. The single arm study that is being used to seek accelerated approval demonstrated a 60% rate of serious adverse events. Almost 9 out of 10 patients required a dose modification due to serous drug reactions. And a quarter of the patients bowed out of the study.
The combination drug that was used in their proposed pivotal — dexamethasone — has a historical response rate of 10-27% at high doses, says the FDA. They could see no response for the drug when used as a monotherapy, and even as a combo they could see only “limited efficacy.”
As for the claimed overall response rate of 25%, most of those were only partial responses.
Another challenge: There are 9 drugs approved for treating multiple myeloma — 4 in the last 4 years. The implicit question there is, why should the agency approve this drug as number 10?
Given the limited efficacy and significant toxicity demonstrated in this population, it is unclear whether treatment with selinexor-dexamethasone provides a clinically meaningful benefit that outweighs the risks of treatment. The limitations of interpreting safety and efficacy from a single arm trial, and lack of single agent activity of selinexor coupled with historical data showing activity of dexamethasone in RRMM, add to the challenges in interpreting the results of the pivotal study in support of the proposed indication.
That’s not good.
Another black eye was earned for the company’s attempt to supply some real world evidence to back up their pitch — which the FDA essentially rejected. And analysts didn’t overlook the voting question: Should the agency wait for the pivotal Phase III data from the BOSTON study before the drug hits the market?
It doesn’t take a genius to fill in the blank on that one.
Jonathan Chang at SVB Leerink notes:
While we were fully expecting the toxicities of selinexor to be a key discussion point, we view questioning the interpretability of selinexor’s efficacy data as a negative surprise. Our MEDACorp KOL checks have indicated that efficacy data from the STORM study suggest that selinexor is an active drug. Notably, some of the efficacy data cited by the FDA for dex alone are generated in an earlier-line patient population (our data tables attached). The draft voting question for the panel is “Should approval of selinexor be delayed until results of the randomized phase 3 trial, BOSTON, are available?”. Recall the Phase III BOSTON study is evaluating selinexor + Velcade + dex (SVd) vs. Velcade + dex (Vd) in relapsed/refractory multiple myeloma with data expected by YE19. Ultimately, potential delay of approval until the BOSTON results are available would be a negative update vs. our assumptions.
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