Delving into the Latest Updates on Andexanet alfa with Synapse

Overview

Basic Info

Drug Type

Recombinant coagulation factor

Synonyms

andexanet alfa, Andexanet alfa (genetical recombination), Andexanet alfa (genetical recombination) (JAN)

+ [17]

Target

factor Xa

Action

inhibitors

Mechanism

factor Xa inhibitors(Factor Xa inhibitors)

Therapeutic Areas

Other Diseases

Active Indication

Hemorrhage

Inactive Indication

Massive hemorrhage

Originator Organization

Portola Pharmaceuticals LLC

Active Organization

AstraZeneca KKAstraZeneca ABBaxter Pharmaceutical Solutions LLC

+ [5]

Inactive Organization

AstraZeneca PLC

Drug Highest PhaseApproved

First Approval Date

United States (03 May 2018),

Hemorrhage

RegulationAccelerated Approval (United States), Orphan Drug (United States), Breakthrough Therapy (United States)

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Structure/Sequence

Sequence Code 14292967

Source: *****

Sequence Code 14449558

Source: *****

This is an observational retrospective database study of hospitalized patients treated with andexanet alfa in approximately 10 Dutch hospitals. Currently there is limited information on the patient characteristics and outcomes of patients who are treated with andexanet alfa in The Netherlands and how it is used. This is of interest for treating clinicians because there is a need for a patient profile, also due to the on par position of andexanet alfa with PCC in the Dutch national guideline.
Analysis of the data showed that 14 patients of the 218 patients included in the study (6.4%) experienced a thrombotic event (TE) within 30 days after treatment with andexanet alfa. The protocol was amended to allow for an in depth analysis of the 14 TE cases.

Start Date06 Oct 2023

Sponsor / Collaborator

AstraZeneca PLC

NCT05548777

/ CompletedNot Applicable

Andexanet Alfa and 4F-PCC Use in Patients Hospitalised With an Anticoagulant-related Major Bleed

This is an observational study based on data collected via an audit of electronic medical charts. The study population will include adult US patients treated with andexanet alfa or 4F-PCC during a hospitalization for an anticoagulation-related major bleed, and their characteristics, treatments and outcomes will be described.

Start Date15 Sep 2022

Sponsor / Collaborator

AstraZeneca PLC

100 Clinical Results associated with Andexanet alfa

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100 Translational Medicine associated with Andexanet alfa

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100 Patents (Medical) associated with Andexanet alfa

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419

Literatures (Medical) associated with Andexanet alfa

01 Feb 2025·Canadian Journal of Emergency Medicine

Andexanet for factor Xa inhibitor-associated acute intracerebral hemorrhage

Author: Green, Robert ; Sharif, Sameer ; Leafloor, Cameron

01 Feb 2025·JOURNAL OF THROMBOSIS AND HAEMOSTASIS

Andexanet-induced heparin resistance in cardiac surgery—a rapid review of case reports and series

Article

Author: Tanaka, Kenichi A ; Boylan, Paul M ; Vandyck, Kofi B ; Townsend, Grace ; Butt, Amir L ; Clifton, Shari C ; Stewart, Kenneth E ; Mishima, Yuko

BACKGROUND:

Andexanet alfa, a Food and Drug Administration (FDA)-approved antidote for apixaban and rivaroxaban, is used to manage life-threatening or uncontrolled bleeding. In patients undergoing cardiopulmonary bypass (CPB), prior exposure to andexanet can cause severe heparin resistance, necessitating effective mitigation strategies. A comprehensive review of such strategies remains lacking.

OBJECTIVE:

To systematically review and characterize cases of andexanet-induced heparin resistance in patients undergoing CPB and to evaluate management strategies.

METHODS:

A systematic search was conducted across multiple databases via the Ovid interface, Cochrane Central Register of Controlled Trials, and the FDA Adverse Event Reporting System. Quality appraisal was performed using a validated instrument for case reports and series describing drug-induced adverse events.

RESULTS:

Fourteen discrete patient cases met inclusion criteria. Post-andexanet administration, the mean initial activated clotting time (ACT) was 199.5 seconds, falling short of a target of >400 seconds despite additional heparin dosing (mean total: 1,123 U/kg). 35.7% of all cases involved thrombus formation in the reservoir; two of which required a circuit replacement. Antithrombin (AT) concentrate was administered to 75% of those received an adjunct therapy. A prophylactic AT use (mean, 49.9 IU/kg) resulted in an ACT over 400 seconds, while its effects in low-dose after the occurrence of thrombosis varied on ACT values. Nafamostat mesylate was used in some cases reported from Japan CONCLUSIONS: Heparin resistance following andexanet exposure poses significant procoagulant risk during CPB. Preemptive high-dose antithrombin therapy may improve ACT values. Further studies are needed to understand the mechanisms and optimize management of this condition.

01 Feb 2025·JOURNAL OF PHARMACY PRACTICE

Development of a Medication-Use Evaluation Template for Andexanet Alfa in the Reversal of Anticoagulation With Factor Xa Inhibitors

Article

Author: Turck, Charles J ; Nussbaum, Barbara B ; Grandoni, Jessica ; Pollack, Charles V ; Fanikos, John ; Fera, Toni ; Spinler, Sarah A ; Moore, Mary R ; Streiff, Michael B ; Burnett, Allison ; Rose, Anne E

Medication-use evaluations are meant to ensure that medication-use processes are consistent with prevailing standards of care, assure optimal use of therapy, and reduce the risk of medication-related problems. Reversal agents for direct oral anticoagulants are a worthy focus for medication-use evaluations for reasons of efficacy, safety, and cost. A multidisciplinary team of experts developed 2 medication-use evaluation templates illustrating the application of professional society guidelines to the appropriate use of andexanet alfa.

40

News (Medical) associated with Andexanet alfa

31 Dec 2024

·www.echemi.com

7 New Drugs Expected to Be Approved in 2025

In 2024, China approved several new drugs, and more blockbuster drugs are expected to be launched in 2025, covering oncology, autoimmune diseases, rare diseases, and other therapeutic areas. Drug Name Mechanism of Action Indications Development Institutions Evantuzumab c-Met/EGFR bispecific antibody Non-small cell lung cancer Johnson & Johnson; Genmab Taqetuzumab CD3/GPRC5D bispecific antibody Multiple myeloma Johnson & Johnson; Genmab Zenidatuzumab Anti-HER2 bispecific antibody Biliary tract cancer Zymeworks; Jazz Pharmaceuticals; BeiGene Inalises PI3Kα inhibitor HR-positive breast cancer Roche; Chugai Pharmaceutical Asunitinib STAMP allosteric inhibitor Speculated use for chronic myeloid leukemia treatment Novartis Tazemetostat EZH2 inhibitor Follicular lymphoma Epizyme; Huadong Medicine; Eisai Relatuzumab-alpha PDL1/TGF-β bispecific antibody Stomach cancer; gastroesophageal junction cancer Hengrui Medicine; Dong-A Pharma Vabysmo EGFR antibody-drug conjugate Nasopharyngeal cancer Lepu Biopharma Tenapanor NHE3 inhibitor Chronic kidney disease hyperphosphatemia Ardelyx; Kyowa Kirin; Fosun Pharma; AstraZeneca Mersutide OXM analog; GLP-1R/GCGR agonist Obesity Eli Lilly; Innovent Biologics Vusirumab IL-1β monoclonal antibody Gouty arthritis Junshi Biosciences Romosozumab SOST monoclonal antibody Osteoporosis Astellas; Amgen; UCB Teplizumab CD3 monoclonal antibody Type 1 diabetes Ligand Pharmaceuticals; Johnson & Johnson; Sanofi Solrepinib Syk inhibitor Immune thrombocytopenic purpura Huadong Medicine BBM-H901 Factor IX gene therapy Hemophilia B Gene Therapy Fitusiran RNAi therapy Hemophilia A; Hemophilia B Sanofi; Alnylam Andexanet alfa Recombinant factor Xa Factor Xa inhibitor antidote Portola Pharmaceuticals Lisocabtagene maraleucel IL-23p19 monoclonal antibody Crohn's disease Boehringer Ingelheim; AbbVie Lemborexant & Daridorexant OX1R antagonist; OX2R antagonist Insomnia Eisai & Idorsia; Sihuan Pharmaceutical; Nxera Pharma Highlights of new drug approvals in 2024 include: 1. Oncology: The world’s first antibody-drug conjugate (ADC) targeting folate receptor alpha (FRα) for ovarian cancer: Mirvetuximab soravtansine. PD-1/VEGF bispecific antibody envafolimab and Nectin-4 ADC enfortumab vedotin. 2. Autoimmune diseases: IL-17A/F monoclonal antibody bimekizumab for ankylosing spondylitis. 3. Rare diseases: Novartis’ complement factor B inhibitor for paroxysmal nocturnal hemoglobinuria (PNH). Blockbuster drugs expected to be approved in 2025 include: Oncology: Amivantamab (Q1) The world’s first c-Met/EGFR bispecific antibody. Highlight: Phase III study showed significant extension of median progression-free survival (mPFS). Talquetamab (Q2) A CD3/GPRC5D bispecific antibody and the world’s first drug targeting GPRC5D. Clinical results: Objective response rate (ORR) in Chinese patients was 69.0%-73.6%. Zanidatamab (Q2) A HER2-targeting bispecific antibody based on Azymetric™ technology. Indication: HER2-positive biliary tract cancer (BTC) with an ORR of up to 52%. Inavolisib (Q3) Roche’s highly selective PI3Kα inhibitor for PIK3CA-mutated breast cancer. Asciminib (Q3) Novartis’ Bcr-Abl allosteric inhibitor for Philadelphia chromosome-positive chronic myeloid leukemia (CML). SHR-1701 (Q4) A PD-L1/TGF-βRII bifunctional fusion protein for first-line treatment of gastric cancer. Phase III study demonstrated significant extension in median overall survival. MRG003 (Q4) China’s first EGFR-targeting ADC with remarkable efficacy in nasopharyngeal carcinoma. Endocrinology and Metabolism: Tenapanor (Q1) The world’s only approved NHE3 inhibitor for controlling hyperphosphatemia in chronic kidney disease patients. Trend Analysis: Continued Innovation in Oncology: The emergence of multiple bispecific antibodies and ADC drugs is making targets and treatment options more precise and diverse. Breakthroughs in Autoimmune and Rare Diseases: New biologics are gradually addressing drug resistance and limited treatment options in previous therapies. Emergence of Domestic Innovative Drugs: Examples include SHR-1701 and MRG003, highlighting the growing research and development capabilities of Chinese pharmaceutical companies. The sequential launch of these drugs will provide new therapeutic options for Chinese patients and enhance China’s position in the global pharmaceutical market.

Drug ApprovalPhase 3Clinical ResultADCImmunotherapy

20 Dec 2024

·www.echemi.com

AstraZeneca's Andexxa Denied Full FDA Approval

Recently, AstraZeneca announced that the FDA has rejected its application for full approval of the drug Andexxa. Andexxa was submitted for market approval in China in December 2022. Initially, it received accelerated approval from the FDA in 2018 and conditional approval from the European Union in 2019. It is primarily used to treat acute bleeding caused by apixaban and rivaroxaban and is the only drug that can specifically reverse the activity of FXa inhibitors, hence being referred to as a "life-saving drug." In 2021, AstraZeneca acquired Alexion for $39 billion, which made Andexxa part of its product line. Reports indicate that Andexxa generated sales of $182 million in 2022, marking a 23% year-on-year increase. The FDA's reason for rejection was that the data provided by AstraZeneca revealed a "significant safety issue": the thrombosis-related mortality rate among patients using Andexxa was twice that of standard treatment. AstraZeneca stated that Andexxa will remain on the U.S. market and plans to collect further data to address the FDA's concerns. If subsequent data is unfavorable, there is a risk of withdrawal from the market. This decision could affect Andexxa's fate in other markets. Currently, its application for market approval in China is still pending, and in March next year, Andexxa's conditional approval in the EU may face stricter scrutiny. "Savage" Drug Reversal Agent With the rapid growth of Xa factor inhibitors such as rivaroxaban and apixaban in thrombotic treatment, these drugs have quickly replaced warfarin as the mainstream anticoagulants. In 2019, the combined sales of rivaroxaban and apixaban reached $16.4 billion, but complaints about bleeding events have also increased. As an antidote to reverse the anticoagulant effects of "saban" drugs, Andexxa can quickly reverse their impact. In 2020, Alexion acquired Andexxa for $1.4 billion, and it subsequently fell under AstraZeneca's umbrella. AstraZeneca has high hopes for Andexxa, with sales continuing to grow, reaching $182 million globally in 2023, a 24% year-on-year increase in the first three quarters. The company is advancing post-marketing clinical trials to seek comprehensive approval. Continuing to Seek Full Approval Industry insiders were surprised by the FDA's rejection. The ANNEXA-I trial conducted in June 2023 showed that Andexxa performed well in hemostatic capability, leading AstraZeneca to terminate the clinical trial early. However, the FDA advisory committee pointed out that the incidence of thrombosis significantly increased among patients using Andexxa. Nevertheless, the FDA's stance was not entirely resolute; committee members suggested modifying the indications and dosage to better assess Andexxa's safety. Currently, AstraZeneca plans to present complete efficacy and safety data at the upcoming medical conference. If supplemental data supports its safety, Andexxa's future remains promising.

Drug ApprovalAcquisitionClinical StudyAccelerated Approval

17 Dec 2024

·www.fiercepharma.com

FDA rejects J&J's subcutaneous Rybrevant filing and AZ's full approval bid for Andexxa

The FDA has sent complete response letters to Johnson & Johnson, rejecting its subcutaneous version of Rybrevant, and to AstraZeneca, giving a thumbs down to its bid for full approval of Andexxa. Johnson & Johnson has received coal in its stocking from the FDA as manufacturing issues have tripped up the company’s attempt to gain approval of its subcutaneous version of lung cancer drug Rybrevant (amivantamab).The U.S. regulator sent J&J a complete response letter (CRL) rejecting its application to clear Rybrevant’s injected formulation for patients with non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations.The FDA also has sent a CRL to AstraZeneca, swatting its request for full approval of Andexxa, which reverses the anticoagulant effect of blood thinners. The thumbs down was not a surprise as it came three weeks after an FDA advisory panel questioned Andexxa’s safety profile.The rejection for J&J was based on observations FDA officials made at a manufacturing facility during a standard pre-approval inspection. The CRL is not related to the formulation of the treatment or its efficacy or safety, the company explained in a release. The agency has not asked J&J to conduct an additional clinical study and its current approval for Rybrevant’s intravenous remains unaffected, the drugmaker added.“We’re working closely with the FDA to bring SC amivantamab to patients as quickly as possible, and are confident in our path to resolution,” Yusri Elsayed, M.D., Ph.D., J&J’s global therapeutic area head for oncology, said in a release. There has been much anticipation for Rybrevant’s injected version since the company reported seven months ago that it had performed better than intravenous Rybrevant in a clinical trial, reducing the risk of death by 38%.In August, the FDA approved Rybrevant and Lazcluse as a first-line treatment for NSCLC with EFGR mutations. A win for SC Rybrevant could help J&J in its challenge against AZ’s EGFR standout Tagrisso, which is an oral drug. While IV Rybrevant can take up to five hours to administer, the SC version only takes up to seven minutes or five minutes at median. As for the FDA's rejection of Andexxa, the company said in an email that it will keep the treatment on the market in the U.S. AZ confirmed the CRL, which was reported last week by Pink Sheet.In the first nine months of this year, Andexxa generated U.S. sales of $61 million and $159 million worldwide, which was up 24% year over year. It has been on the market since 2018 when Portola Pharmaceuticals scored its accelerated approval.In 2020, Alexion bought out Portola in a much-criticized $1.4 billion deal. A year later, AZ acquired Alexion.

Drug ApprovalAcquisitionAccelerated Approval

100 Deals associated with Andexanet alfa

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External Link

KEGG	Wiki	ATC	Drug Bank
D11029	Andexanet alfa	V03AB38	DB14562

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Hemorrhage	United States	AstraZeneca AB	03 May 2018
Hemorrhage	United States	Portola Pharmaceuticals LLC	03 May 2018

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Massive hemorrhage	Phase 3	United States	AstraZeneca PLC	02 Aug 2024
Massive hemorrhage	Phase 3	China	AstraZeneca PLC	02 Aug 2024
Massive hemorrhage	Phase 3	Japan	AstraZeneca PLC	02 Aug 2024
Massive hemorrhage	Phase 3	Argentina	AstraZeneca PLC	02 Aug 2024
Massive hemorrhage	Phase 3	Australia	AstraZeneca PLC	02 Aug 2024
Massive hemorrhage	Phase 3	Austria	AstraZeneca PLC	02 Aug 2024
Massive hemorrhage	Phase 3	Belgium	AstraZeneca PLC	02 Aug 2024
Massive hemorrhage	Phase 3	Brazil	AstraZeneca PLC	02 Aug 2024
Massive hemorrhage	Phase 3	Bulgaria	AstraZeneca PLC	02 Aug 2024
Massive hemorrhage	Phase 3	Canada	AstraZeneca PLC	02 Aug 2024

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03661528 (ANNEXA-I, CTgov)	Phase 4	Intracranial Hemorrhages	530	andexanet alfa (Andexanet Alfa)	pmuqxiqxeq = cfxdsojpjg kjzusyujnk (obrppkkfhn, ozknlahurq - ttaptvcyvo) View more	-	03 Jul 2024
				Usual care (Usual Care)	pmuqxiqxeq = ozzssgjffm kjzusyujnk (obrppkkfhn, eyxsvfvlga - tootuqjtlt) View more
NCT03661528 (Pubmed) Manual	Phase 4	Cerebral Hemorrhage	530	Andexanet alfa	ibdxzbstry(zpnkgavizw) = kbjcubzwhm vffqwkbzob (vyjqvljhfc ) View more	Positive	16 May 2024
				Andexanet (Usual care)	ibdxzbstry(zpnkgavizw) = yqyhunqhfu vffqwkbzob (vyjqvljhfc ) View more
ISC2024	Not Applicable	Cerebral Hemorrhage antiXa	103	Prothrombin complex concentrate (PCC)	swcczsvwgy(hpudjvjdfa) = npjmlgzhtr wfxtrtztfg (cqossznsxt ) View more	Positive	01 Feb 2024
ISTH2023	Not Applicable	Hemorrhage	-	Andexanet alfa	qnmcqvdfgw(njbkxqhfmn) = tkvfzpskrk qeanszolqs (rfkehparys )	-	24 Jun 2023
				4-Factor Prothrombin Complex Concentrate (4F-PCC)	qnmcqvdfgw(njbkxqhfmn) = fbxoohkusf qeanszolqs (rfkehparys )
ISTH2023	Not Applicable	Hemorrhage factor Xa (FXa) inhibitors rivaroxaban \| apixaban	-	Andexanet alfa	kxhakihbev(nqmwmwjepf) = lloggzlsjy aqfkniteqb (hmvrppnafa ) View more	-	24 Jun 2023
				4-factor prothrombin complex concentrate	kxhakihbev(nqmwmwjepf) = uawhjaxnbn aqfkniteqb (hmvrppnafa ) View more
ISTH2022	Not Applicable	-	-	Unfractionated Heparin (UFH)	tlziejsoqt(qtulbrwuqo) = rmmuihuhdt dncjgcadso (aowlpwunnq )	-	09 Jul 2022
				Enoxaparin	tlziejsoqt(qtulbrwuqo) = qtgxaiezee dncjgcadso (aowlpwunnq )
ISTH2022	Not Applicable	-	-	Andexanet alfa	iqwpavxjjp(hxpaeidqpb) = wgsltclgwk mlnnojfhre (csqbquolbu )	-	09 Jul 2022
				4F-PCC	iqwpavxjjp(hxpaeidqpb) = fnznlbfbgh mlnnojfhre (csqbquolbu )
AAN2022	Not Applicable	Cerebral Hemorrhage DOAC type	43	Andexanet alfa	gqtzqzaopw(llhnoszthi) = wttfnlivrk hnpnmvxopc (xvovpxxuth )	-	03 May 2022
ISTH2021	Not Applicable	-	-	Anti-Xa agents (oral)	esyvfxyykq(vqffpstofu) = okdujelxha pjgldqduje (cqkqwwdnaw )	-	17 Jul 2021
				Anti-Xa agents (parenteral)	esyvfxyykq(vqffpstofu) = uyrzongans pjgldqduje (cqkqwwdnaw )
ISC2021	Not Applicable	Cerebral Hemorrhage	604	Andexanet alfa	nlzypuauhj(tvgjpawkoa) = nueejsooie mkcsojemln (nlrzdofeuf, 3 - 8)	-	01 Mar 2021

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Biosimilar

Competitive landscape of biosimilars in different countries/locations. Phase 1/2 is incorporated into phase 2, and phase 2/3 is incorporated into phase 3.

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Competitive landscape of biosimilars in different countries/locations. Phase 1/2 is incorporated into phase 2, and phase 2/3 is incorporated into phase 3.

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Andexanet alfa

Overview

Basic Info

Structure/Sequence

Related

External Link

R&D Status

Clinical Result

Translational Medicine

Deal

Core Patent

Clinical Trial

Approval

Biosimilar

Regulation