Portola plunges as PhIII blood thinner misses key goal in head-to-head comparison study

Portola CEO William Lis

Portola's ($PTLA) late-stage anticlotting drug betrixaban has stumbled badly in the last leg of its run-up to filing a new drug application.

The biotech announced this morning that the Factor Xa inhibitor failed to outperform the standard of care in a key cohort of the sickest high-risk patients, even though two other group assessments fared better. And signs of trouble for the late-stage effort triggered a 32% plunge in the biotech's stock value.

The trouble for South San Francisco-based Portola--a 2009 Fierce 15 company--centered on cohort 1 in the study, centering on heart attack and stroke victims with elevated D-dimer levels, which made up 62% of the overall study population. Doctors run D-dimer tests to check patients' risk for threatening conditions like deep vein thrombosis or a pulmonary embolism.

In that group betrixaban just missed the standard for proving its superiority to injectable enoxaparin (Lovenox) in preventing blood clots.

In the sequential study design that Portola adopted for the trial, that should have been the end of the trial. But investigators went on to do the numbers on two more cohorts, and came up with better data. A separate cohort of high-risk patients 75 and over was included in the study, along with an account on all of the patients. That older group and the overall population did fare better than the SoC arms. 

Portola noted that there was no statistically significant difference between standard of care and their drug in major bleeding events in any of the three cohorts.

Portola CEO Bill Lis insisted that when the company gets a chance to review all of the data in a few months, they will be able to convince analysts and regulators that the therapy overall spurred a positive, clinically relevant outcome, though he also noted that some analysts may not see it that way now. 

"This was unexpected," he noted in a call with analysts. There was less efficacy than expected and a "lot less bleeding than we've seen before."

Portola had been on a roll up to now. Investigators have been putting out a drumbeat of positive trial assessments for its anti-anticoagulant andexanet alfa, noting its ability to reverse the effects of blood thinners like Xarelto and Eliquis, a safety measure that can be turned to in order to prevent the threat of major bleeding events among patients. The drug prompts Factor Xa inhibitors to turn away from the enzymes they target, essentially acting as a decoy.

- here's the release