Complete Response for Andexxa (andexanet) to convert accelerated approval to full approval to reverse the effects of direct-oral anticoagulants – AstraZeneca

AstraZeneca PLC’s anticoagulant reversal agent Andexxa (andexanet) will not convert to full approval, after the FDA  issued a complete response letter for the supplemental biologics license application. The next steps for the drug following the CRL, which has not been publicly announced by the company, are unclear. Neither AstraZeneca nor FDA would provide much additional information about the product’s standing.

An FDA decision on the product was expected at the end of November.. The agency could move to withdraw the drug from the market or ask the company to conduct additional studies to verify a favorable risk-benefit balance. AstraZeneca stated that the drug will remain on the US market while discussions with the agency about next steps continue. But the company would not comment on whether those discussions include potential new trials. AstraZeneca further stated that the drug will remain on the US market while discussions with the agency about next steps continue.

Andexxa is the only treatment currently indicated to reduce the effects of direct oral FXa inhibitors, Bristol-Myers Squibb Co./Pfizer Inc.’s Eliquis (apixaban) and Johnson & Johnson/Bayer AG’s Xarelto (rivaroxaban), when reversal of anticoagulation is needed due to life-threatening or uncontrolled bleeding.

The admission seems notable since the FDA raised efficacy and safety concerns about the drug’s confirmatory trial ANNEXA-I before a 21 November advisory committee meeting. Among them was an increased risk of thrombosis-related deaths. The Cellular, Tissue and Gene Therapies Advisory Committee (CTGTAC) suggested that the unfavorable risk-benefit balance seen in the confirmatory trial may be due to the population studied, patients with acute intracranial hemorrhage (ICH). The group is generally older and sicker and may be more susceptible to adverse events than other indicated populations. The committee said the indication could be modified to include patients more likely to have a favorable risk-benefit. Some also suggested modifying the Andexxa dose.

The lack of other available products to reverse the effects of direct-oral anticoagulants weighed heavily on the committee members as they considered the confirmatory trial data, as well as open public hearing testimony from emergency room doctors in favor of maintaining availability.