On Thursday, the Cellular, Tissue, and Gene Therapies Advisory Committee will discuss AstraZeneca Plc's (NASDAQ:AZN) supplemental biologics license application for Andexxa (coagulation factor Xa (recombinant), inactivated -zhzo), for patients treated with rivaroxaban or apixaban when reversal of anticoagulation is needed due to life-threatening or uncontrolled bleeding.

The FDA initially granted accelerated approval of Andexxa, a recombinant modified human factor Xa (FXa) protein, in 2018 based on the change from baseline in anti-activated FXa (anti-FXa) activity, as a surrogate endpoint reasonably likely to predict clinical benefit as provided for in 21 CFR 601.41.

AstraZeneca was required to conduct a randomized controlled trial to verify and describe the clinical benefit of Andexxa, due to uncertainty as to the relation of the surrogate endpoint to clinical benefit and the observed clinical benefit to ultimate outcomes in the indicated population. In January 2024, the company submitted a supplemental Biologics Licensing Application for Andexxa with the results of the ANNEXA-I trial to fulfill this requirement.

Before the meeting, the FDA panel released brief documents highlighting some safety issues and other concerns.

"Although andexanet showed superiority of the primary efficacy endpoint over UC [usual care] within the PEP [primary efficacy population], the superior efficacy at 12 hours did not predict longer-term benefit," FDA said.

The major safety findings included a doubling of the rate of thromboses and thrombosis-related deaths at Day 30 in the andexanet arm compared with UC.

The major topics for discussion:

• ANNEXA-I demonstrated an increased incidence of thrombosis (14.6% versus 6.9%) and thrombosis-related deaths at Day 30 (2.5% versus 0.9%) in the andexanet arm compared with the UC arm, respectively. These findings raise concerns regarding whether the serious risks of treatment with andexanet are acceptable in the indicated population.
• While the primary efficacy endpoint in ANNEXA-I was met, the treatment difference across arms appears to be primarily driven by one of three components of the composite endpoint, namely the volume of hematoma at 12 hours, while other clinically meaningful endpoints were not different between the two arms. These findings raise the question as to whether the benefit demonstrated in ANNEXA-I outweighs the serious risks.

The document highlighted, "Treatment with andexanet demonstrated a statistically significant improvement in hemostasis compared to UC (andexanet: 65.7% versus UC: 53%). The observed treatment difference between arms appears to be primarily driven by hematoma volume, with more patients in the andexanet arm than UC arm experiencing a ≤35% increase from baseline in hematoma volume at 12 hours (74% versus 60%)."

Hematoma is a blood collection that pools outside blood vessels, usually caused by an injury or surgery.

Price Action: AZN stock is up 0.97% at $63.82 at last check Thursday.

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Image created using artificial intelligence via Midjourney.