Telecom tycoon's phase 3 pancreatic cancer bet flames out, sending stock to the basement

Rafael Pharmaceuticals' bet on the rock-hard pancreatic cancer indication has blown up in its face. The pivotal trial found devimistat had no effect on overall survival—and, as a kicker, another phase 3 in a blood cancer was stopped early for futility.

Encouraged by signs of efficacy in a single-arm, single-site study that enrolled 18 subjects, Rafael took devimistat, also known as CPI-613, into a phase 3 trial in 2018. The pivotal trial randomized 500 or so pancreatic cancer patients to receive Folfirinox or a combination of devimistat and a modified version of the standard-of-care chemotherapy regimen.

Devimistat failed. Badly. Median overall survival (OS) in the Folfirinox arm was 11.7 months, in line with the result of a trial published a decade ago that demonstrated the efficacy of the regimen. Devimistat fell short of the bar set by Folfirinox, chalking up a median OS of 11.1 months. 

The result caused the study to miss its primary endpoint. Rafael originally set out to show the effect of devimistat on response rates before changing the primary endpoint to, first, progression-free survival (PFS) and, finally, OS. The company is yet to share response rate or PFS data, but the trial is a washout in terms of OS.

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Pancreatic cancer was one of two phase 3 opportunities for devimistat. The second trial, which could have provided a glimmer of hope amid the wreckage of the pancreatic cancer study, has flamed out at the same time, with the independent data monitoring committee recommending Rafael stop the acute myeloid leukemia trial because of the lack of efficacy seen in an interim analysis. 

The twin failures leave the prospects of studies testing devimistat in other solid tumors and blood cancers in doubt. Rafael is going after clear cell sarcoma, biliary tract cancer and colorectal cancer on the solid tumor side, as well as a clutch of hematological malignancies. Hopes for both sides of the pipeline were hit by the twin failures.   

That crushing of hopes manifested in a 75% drop in the share price of Rafael Holdings, sending the stock spiraling down to below $8 in premarket trading. Rafael Holdings is an umbrella company set up by telecommunications tycoon Howard Jonas. In June, Jonas outlined plans to merge the holding and pharma companies to create a late-stage clinical oncology company.