AstraZeneca’s Andexxa Faces FDA Scrutiny Over Effectiveness, Security Issues – AstraZeneca (NASDAQ:AZN)

On Thursday, the Mobile, Tissue, and Gene Therapies Advisory Committee will focus on AstraZeneca Plc’s AZN supplemental biologics license software for Andexxa (coagulation issue Xa (recombinant), inactivated -zhzo), for sufferers handled with rivaroxaban or apixaban when reversal of anticoagulation is required on account of life-threatening or uncontrolled bleeding.

The FDA initially granted accelerated approval of Andexxa, a recombinant modified human issue Xa (FXa) protein, in 2018 based mostly on the change from baseline in anti-activated FXa (anti-FXa) exercise, as a surrogate endpoint fairly more likely to predict medical profit as supplied for in 21 CFR 601.41.

AstraZeneca was required to conduct a randomized managed trial to confirm and describe the medical good thing about Andexxa, on account of uncertainty as to the relation of the surrogate endpoint to medical profit and the noticed medical profit to final outcomes within the indicated inhabitants. In January 2024, the corporate submitted a supplemental Biologics Licensing Software for Andexxa with the outcomes of the ANNEXA-I trial to satisfy this requirement.

Earlier than the assembly, the FDA panel launched brief paperwork highlighting some issues of safety and different considerations.

“Though andexanet confirmed superiority of the first efficacy endpoint over UC [usual care] throughout the PEP [primary efficacy population], the superior efficacy at 12 hours didn’t predict longer-term profit,” FDA mentioned.

The most important security findings included a doubling of the speed of thromboses and thrombosis-related deaths at Day 30 within the andexanet arm in contrast with UC.

The most important matters for dialogue:

• ANNEXA-I demonstrated an elevated incidence of thrombosis (14.6% versus 6.9%) and thrombosis-related deaths at Day 30 (2.5% versus 0.9%) within the andexanet arm in contrast with the UC arm, respectively. These findings increase considerations relating to whether or not the intense dangers of therapy with andexanet are acceptable within the indicated inhabitants.
• Whereas the first efficacy endpoint in ANNEXA-I used to be met, the therapy distinction throughout arms seems to be primarily pushed by certainly one of three elements of the composite endpoint, particularly the quantity of hematoma at 12 hours, whereas different clinically significant endpoints weren’t completely different between the 2 arms. These findings increase the query as as to whether the profit demonstrated in ANNEXA-I outweighs the intense dangers.

The doc highlighted, “Remedy with andexanet demonstrated a statistically vital enchancment in hemostasis in comparison with UC (andexanet: 65.7% versus UC: 53%). The noticed therapy distinction between arms seems to be primarily pushed by hematoma quantity, with extra sufferers within the andexanet arm than UC arm experiencing a ≤35% enhance from baseline in hematoma quantity at 12 hours (74% versus 60%).”

Hematoma is a blood assortment that swimming pools exterior blood vessels, normally brought on by an harm or surgical procedure.

Worth Motion: AZN inventory is up 0.97% at $63.82 finally test Thursday.

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