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Posts Tagged ‘Antidote’

NO FDA Approval Yet for Andexanet

| Anticoagulants, Bleeding, Therapy, Uncategorized | Comments Off on NO FDA Approval Yet for Andexanet

Stephan Moll, MD writes… The FDA did NOT approve Andexanet (brand names: AndexXa in the US, IndexXa in Europe) in a decision on August 18th, 2016.  Andexanet is the antidote in clinical development to reverse the anticoagulant effect of Eliquis® (rivaroxaban), Savaysa® (edoxaban), Xarelto® (rivaroxaban) and Lovenox® (enoxaparin).  The FDA is said to have requested more information from the company (Portola) making Andexanet, specifically (a) additional information related to manufacturing of the drug, and (b) more data to support inclusion of Savaysa® and Lovenox®  in the label.  The FDA also wants to finalize its review of the company’s proposals for post-marketing data collection on the performance of the drug.

It needs to be seen when the company (Portola) submits the requested additional information to the FDA and when a new decision from the FDA is then to be expected.  My guess is that this will be sometime in 2017.

 

References

  1. Portola announcement from Aug 18, 2016: http://bit.ly/2c1wKaK
  2. Connolly SJ et al. Andexanet alfa for acute major bleeding associated with factor Xa inhibitors. NEJM 2016;Aug 30 [e-pub]
     (http://dx.doi.org/10.1056/NEJMoa1607887)

 

Disclosure:  I have consulted for Portola, Janssen, and Boehringer-Ingelheim.

Last updated: Aug 31st, 2016

Antidote for New Oral Xa-Inhibitors (Eliquis, Xarelto): Phase 2 Study

| Eliquis, Uncategorized | Comments Off on Antidote for New Oral Xa-Inhibitors (Eliquis, Xarelto): Phase 2 Study

Stephan Moll, MD writes….

The pharmaceutical company Portola reported today (May 8th, 2013) without many details on the  findings of their phase 2 human volunteer study of their anti-Xa anticoagulant antidote PRT4445 — ClinicalTrials.gov Identifier: NCT01758432 (study description here). In this study, healthy volunteers who had taken Eliquis (Apixaban) received the antidote.  The study showed a “rapid and sustained and dose-related reversal of the anticoagulant activity of Eliquis” (thrombin generation and anti-factor Xa activity) and “no serious adverse events”.

PRT4445 is a recombinant  molecule, structurally very similar to native factor Xa, but with some modifications that make it inactive as a clotting factor.  It acts as a decoy for factor Xa inhibitor drugs, binding them. Once they are bound they are unable to bind to and inhibit native factor Xa. Thus, the native factor Xa becomes available to participate in the coagulation process and normal hemostasis is restored.

The full Portola report is here.  The data of the study still need to be presented at a medical meeting and published.  At this point all that can be concluded is that the drug is reported to have an ex vivo effect on coagulation tests.  Whether it has any clinical efficacy in major bleeding associated with Eliquis or any of the other new oral anti-Xa anticoagulants (Xarelto=rivaroxaban; Edoxaban) has yet to be investigated.

 

Disclosure:  I have consulted for Janssen, Boehringer-Ingelheim, and Daiichi.

Last updated:  May 8th, 2013