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The US Food and Drug Administration (FDA) approved betrixaban (Bevyxxa), a new oral anticoagulant for prevention of venous thromboembolism (VTE) in hospitalized medical patients with risk factors for DVT/PE.
With betrixaban, manufacturer Portola will seek to expand a tiny market niche it could immediately dominate: prophylaxis of DVT/PE extending for about a month after hospital discharge into the outpatient setting. Betrixaban is the only oral drug approved for this indication. Its competition, subcutaneously injected enoxaparin, is rarely used after hospital discharge except in the highest-risk patients.
The FDA approved betrixaban with a fast-track designation and priority review, based on the APEX study comparing extended-duration betrixaban (35 - 42 days) to short-duration enoxaparin (Lovenox) (6 - 14 days) for prevention of DVT/PE in 7,513 hospitalized medical patients with VTE risk factors.
That study was actually negative, showing no benefit of extended betrixaban over short-term enoxaparin in the prespecified cohort. Portola likely chose that smaller subset of patients (those with an elevated d-dimer) expecting the largest benefits to be found there. Ironically, betrixaban's benefits just missed statistical significance in that group, but were seen in the overall study population. Portola's stock tanked 30% on the announcement of the APEX results.
Portola then published another analysis of the APEX data and worked with the FDA who found enough efficacy in the overall data sets for approval. Efficacy was measured in 7,441 patients by a composite outcome score comprised of either the occurrence of asymptomatic or symptomatic proximal deep vein thrombosis, non-fatal pulmonary embolism, or VTE-related death. Only 4% of patients taking betrixaban experienced such events compared with 6% of those taking enoxaparin (relative risk 0.75, 95% CI: 0.61, 0.91). These weren't the same endpoints used in the APEX study, which used a composite of asymptomatic DVT and symptomatic DVT/PE. This efficacy data seems to come from the later post hoc analyses.
Apparently investors weren't expecting the good news: Portola's stock price increased 47% on the announcement.
Adverse reactions including bleeding were similar between betrixaban and enoxaparin.
The recommended dose of betrixaban is an initial single dose of 160 mg starting on day 1, followed by 80 mg once daily taken for 35 to 42 days at the same time each day with food.
Betrixaban represents a "major advance for the field of thrombosis. It is the first therapy to demonstrate a reduction in the incidence of VTE in these high-risk patients without a significant increase in major bleeding," APEX investigator C. Michael Gibson, MD, professor at Harvard Medical School in Boston, Massachusetts, said in the company news release.
Portola announced its hopes to launch Bevyxxa between August and November 2017.
Betrixaban has the potential to change care standards if marketing efforts successfully nudge physicians toward routine "just in case" DVT prophylaxis post-hospital discharge for a significant portion of the millions of medical patients hospitalized annually.