Portola (PTLA) drops after disappointing drug trial

Portola Pharmaceuticals Inc. said its blood-clot treatment, an oral drug, showed no statistical difference in treating the condition than the current standard of care, an injectable blood thinner, according to the results of a phase-3 trial.

The APEX study tested betrixaban against Sanofi's approved injectable anticoagulant, Lovenox (enoxaparin), in patients at risk for blood clots after being hospitalized for a number of common medical conditions, including heart failure or infection. Portola used a unique study design in an attempt to enrich the trial and improve its odds of success.

That might ultimately be betrixaban’s undoing.

Betrixaban outperformed enoxaparin in the study’s overall patient population (an impressive 7,500 patients globally), and in Cohort 2, those with elevated D-dimer (a protein fragment present after a blood clot has developed) or ≥75 years of age. But betrixaban missed in a predefined subset of patients dubbed Cohort 1: high-risk patients with elevated D-dimer levels. The study’s primary endpoint was the relative risk of deep venous thrombosis, non-fatal pulmonary embolism, or venous thromboembolism-related death.
(Corrected to reflect that both the overall population and Cohort 2 achieved a p-value of <0 .05.="" p="">The study called for an efficacy analysis of Cohort 1 first, and required a p-value of 0.05 or less in order to test Cohort 2. The second analysis also required a p-value of 0.05 or less in order to test the overall study population.

Cohort 1 achieved a p-value of 0.054, just shy of the threshold for further analysis of the program. Per protocol, that should have been the end. But Portola went ahead with Cohort 2 and overall analysis anyway. Cohort 2 and the overall study population achieved p-values of 0.029 and 0.006, respectively.