Karyopharm fishes for a win as its solid tumour bid flounders

The problem with setting clear expectations is that when they are missed there is nowhere to hide. Hence Karyopharm was punished today as it unveiled topline results from Siendo, a study of Xpovio that strictly speaking succeeded but generated a smaller effect size than hoped. The trial was looking for a three-month PFS advantage and hazard ratio of 0.6, but missed this by a hefty margin and only just scraped statistical significance. Siendo was conducted in advanced endometrial cancer and represents Karyopharm’s best shot of moving Xpovio, which is already approved in multiple myeloma, into solid tumours; shares in the company plunged 20% at the open. Investors were unconvinced by what appeared to be a remarkable finding in a prespecified subgroup, carriers of the wild-type p53 gene, which Karyopharm said is found in half of endometrial cancer patients. Such a strong signal in an easily defined patient group could be considered a win, but it was revealing that on a call executives insisted that they remained focused on the opportunity in all patients. This raises the prospect of these super-responders disappearing on closer inspection of the data, whose full disclosure will be keenly awaited.

Siendo: fishing for a win or landing the super-responders?
  Xpovio Placebo  Hazard ratio (p value)
Median PFS in all-comers (n=263) 5.7 3.8 0.70 (p=0.0486)
Median PFS in wild-type p53 (n=103) 13.7 3.7 0.38 (p=0.0006)
Note: trial randomised 2:1. Source: company press release. 

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