Andexanet alfa (1) – Ondexxya®

• Clinical trials
  • The pharmaceutical manufacturer has submitted the single-arm, multicentre registration trial ANNEXA-4 for andexanet alfa.
  • The RETRACE-II study is a retrospective German observational(registry) study, which included 1,338 patients from 19 university centres who, between 1 January 2011 and 31 December 2015, suffered an intracerebral haemorrhage associated with a vitamin K antagonistor a non-vitamin K-dependent oral anticoagulant-associated intracerebral haemorrhage.

Adult patients being treated with a direct factor Xa (FXa) inhibitor (apixaban or rivaroxaban) when the anticoagulation must be repealed due to life-threatening or uncontrollable bleeding.

• For adult patients being treated with a direct factor Xa (FXa) inhibitor (apixaban or rivaroxaban) where repeal of anticoagulation is required due to life-threatening or uncontrollable bleeding, the additional benefit compared with the appropriate comparator therapy is not proven.
• The benefit assessment was not based on any direct comparative data between andexanet alfa and the appropriate comparator therapy.
• Overall, the data presented for the PS-adjusted comparison are therefore not suitable for inferring any additional benefit for andexanet alfa compared with the appropriate comparator therapy.
• mortality
  • There is no statistically significant difference between the two groups in either the neurological function endpoint or in mortality.
• Morbidity – change in volume of the intracerebral haemorrhage lesion
  • However, the observed effect is not large enough to rule out the possibility that it could be explained solely by systematic bias.
  • Furthermore, it is unclear how this endpoint is reflected in patient-relevant endpoints, such as neurological function or mortality.
• Morbidity – Neurological function (Modified Rankin Scale)
  • No statistically significant difference was observed between the two groups for either the neurological function endpoint or mortality.
• Side effects
  • Furthermore, no comparative data on adverse event endpoints are available, meaning it is not possible to weigh up the benefits and harms of the intervention against the appropriate comparator therapy.
• Overall assessment
  • The patient characteristics of the studies used for the propensity score-adjusted comparison do not show sufficient similarity, particularly with regard to the severity of intracerebral haemorrhages.
  • Although there is a statistically significant difference in favour of andexanet alfa for the endpoint of change in the volume of the intracerebral haemorrhage lesion, the effect is not large enough to rule out the possibility that it could be explained solely by systematic bias.
  • Furthermore, it is unclear how this endpoint is reflected in patient-relevant endpoints, such as neurological function or mortality.
  • No statistically significant difference was observed between the two groups for either the ‘neurological function’ endpoint or the mortality endpoint.
  • Furthermore, no comparative data on adverse event endpoints are available, meaning it is not possible to weigh up the benefits and harms of the intervention against the appropriate comparator therapy.
  • Overall, the data presented are therefore not sufficient to demonstrate any additional benefit of andexanet alfa compared with the appropriate comparator therapy.

Courtesy translation only, please refer to the German original.