Delving into the Latest Updates on Andexanet alfa with Synapse

Overview

Basic Info

Drug Type

Recombinant coagulation factor

Synonyms

Andexanet alfa (USAN/INN), Andexanet alfa (genetical recombination), Andexanet alfa (genetical recombination) (JAN)

+ [17]

Target

factor Xa

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 ABBaxter Pharmaceutical Solutions LLCAstraZeneca Global R&D (China) Co., Ltd.

+ [5]

Inactive Organization

AstraZeneca PLC

Drug Highest PhaseApproved

First Approval Date

US (03 May 2018),

Hemorrhage

RegulationBreakthrough Therapy (US), Orphan Drug (US), Accelerated Approval (US)

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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.

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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466

Literatures (Medical) associated with Andexanet alfa

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

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.

01 Jan 2025·Arteriosclerosis, Thrombosis, and Vascular Biology

Andexanet Alfa–Associated Heparin Resistance in Cardiac Surgery: Mechanism and In Vitro Perspectives

Article

Author: Frederiksen, James W. ; Chabata, Charlene V. ; Patel, Prakash A. ; Sullenger, Bruce A. ; Yu, Haixiang ; Thalji, Nabil K. ; Ke, Lei

BACKGROUND:Andexanet alfa (andexanet) is the only Food and Drug Administration–approved antidote for direct FXa (factor Xa) inhibitors but has been reported to cause resistance to unfractionated heparin (UFH). This has delayed anticoagulation for procedures requiring cardiopulmonary bypass. The mechanism, andexanet and UFH dose dependence, and thrombotic risk of andexanet-associated heparin resistance are unknown.METHODS:The effect of andexanet in vitro was determined using activated clotting times and thromboelastography. Ex vivo cardiopulmonary bypass circuits were used to determine whether andexanet impaired anticoagulation for extracorporeal circulation. Kinetics of AT (antithrombin) inhibition of FXa and thrombin were measured in the presence of andexanet. Equilibrium modeling and thrombin generation assay validation were used to predict the role of andexanet, AT, and UFH concentrations in andexanet-associated heparin resistance.RESULTS:Andexanet prevented UFH-mediated prolongation of activated clotting times and thromboelastography times. At lower concentrations of andexanet, heparin resistance could be overcome with suprapharmacologic doses of UFH, but not at higher andexanet concentrations. Andexanet rendered standard doses of UFH inadequate to prevent circuit thrombosis, and suprapharmacologic UFH doses were only partially able to overcome this. Scanning electron microscopy demonstrated coagulation activation in circuits. Andexanet prevented UFH enhancement of AT-mediated inhibition of FXa and thrombin. Equilibrium modeling and thrombin generation assay validation demonstrated that andexanet creates a triphasic equilibrium with UFH and AT: initial UFH unresponsiveness, normal UFH responsiveness when andexanet is depleted, and finally AT depletion. Sufficient cardiopulmonary bypass heparinization can only occur at low therapeutic andexanet doses and normal AT levels. Higher andexanet doses or AT deficiency may require high UFH doses and potentially AT supplementation.CONCLUSIONS:Andexanet causes heparin resistance due to redistribution of UFH-bound AT. If andexanet cannot be avoided before heparinization and direct thrombin inhibitors are undesirable, our in vitro study suggests excess UFH should be considered as a potential strategy before AT supplementation.

01 Jan 2025·Emergency Medicine Journal

Correspondence on ‘Four-factor prothrombin complex concentrate versus andexanet alfa for the reversal of traumatic brain injuries’ by Sadeket al

Letter

Author: Sadek, Erin ; Hecht, Jason

23

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

16 Dec 2024

·endpts.com

AstraZeneca is denied full FDA approval of Andexxa following critical advisory meeting

AstraZeneca said the FDA declined to fully approve its anticoagulant reversal drug Andexxa, less than a month after an advisory committee meeting at which the agency and a group of outside advisors were skeptical of accompanying data. The company confirmed receipt of a complete response letter in a statement to Endpoints News on Tuesday, saying the drug will remain on the US market. The FDA didn’t immediately respond to a request for comment. The rejection was first reported by Pink Sheet . The decision comes a year-and-a-half after AstraZeneca stopped a confirmatory trial of the drug early. At the time, the UK pharma halted the trial at the recommendation of the trials data safety and monitoring board, after efficacy signals were identified earlier than expected. Though Andexxa did spur a statistically significant improvement in the body’s ability to naturally halt bleeding compared with a standard-of-care agent, FDA advisory committee members raised issues with the safety profile . And the FDA itself said there were “major safety findings,” including a doubling of blood-clot related deaths, compared with the standard of care. FDA advisors also questioned the trial’s positive efficacy signal and whether the change in hematoma volume was a proper primary endpoint. Andexxa has changed hands a number of times over the years, having first snagged accelerated approval in 2018 while owned by Portola. It was originally rejected before receiving an accelerated approval to reverse Factor Xa inhibitors such as Xarelto and Eliquis. Portola was then acquired by Alexion in 2020, which was then acquired by AstraZeneca for $39 billion in 2021.

AcquisitionAccelerated ApprovalDrug 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	US	AstraZeneca AB	03 May 2018
Hemorrhage	US	Portola Pharmaceuticals LLC	03 May 2018

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Hemorrhage	NDA/BLA	CN	Baxter Pharmaceutical Solutions LLC	16 Dec 2023
Hemorrhage	NDA/BLA	CN	AstraZeneca AB	16 Dec 2023
Hemorrhage	NDA/BLA	CN	AstraZeneca Global R&D (China) Co., Ltd.	16 Dec 2023
Massive hemorrhage	Phase 2	US	AstraZeneca PLC	02 Aug 2024
Massive hemorrhage	Phase 2	CZ	AstraZeneca PLC	02 Aug 2024
Massive hemorrhage	Phase 2	DK	AstraZeneca PLC	02 Aug 2024
Massive hemorrhage	Phase 2	MY	AstraZeneca PLC	02 Aug 2024
Massive hemorrhage	Phase 2	AT	AstraZeneca PLC	02 Aug 2024
Massive hemorrhage	Phase 2	PT	AstraZeneca PLC	02 Aug 2024
Massive hemorrhage	Phase 2	DE	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)	kbsgaoydnt(evddtmcqlc) = ihrmvlfisx dsbdtrpiqp (axzivxmgaa, rblajrlzci - rmljhtldey) View more	-	03 Jul 2024
				Usual care (Usual Care)	kbsgaoydnt(evddtmcqlc) = miyoijcuep dsbdtrpiqp (axzivxmgaa, guvwggpnjs - yguypgzbwe) View more
NCT03661528 (Pubmed) Manual	Phase 4	Cerebral Hemorrhage	530	Andexanet alfa	(pzywlzigge) = ncjabkyckw dzvouisals (rldloewwsw ) View more	Positive	16 May 2024
				Andexanet (Usual care)	(pzywlzigge) = cuiborhobn dzvouisals (rldloewwsw ) View more
ISTH2023	Not Applicable	Hemorrhage	-	Andexanet alfa	(qehatushwv) = dzuyjtkmgb lgocudgrbg (nhnxzfcyzk )	-	24 Jun 2023
				4-Factor Prothrombin Complex Concentrate (4F-PCC)	(qehatushwv) = orhpuypmly lgocudgrbg (nhnxzfcyzk )
ISTH2023	Not Applicable	Hemorrhage factor Xa (FXa) inhibitors rivaroxaban \| apixaban	-	Andexanet alfa	kigbmecwvo(ohdzqecghd) = uazhjbbueb rhutlfvrfo (tkzouygvdg ) View more	-	24 Jun 2023
				4-factor prothrombin complex concentrate	kigbmecwvo(ohdzqecghd) = movyoynday rhutlfvrfo (tkzouygvdg ) View more
ISTH2022	Not Applicable	-	-	Unfractionated Heparin (UFH)	oczbsykkrc(ypbnugxukq) = qzbgzlqutx qldsbqdxxt (dnmvrmyrpc )	-	09 Jul 2022
				Enoxaparin	oczbsykkrc(ypbnugxukq) = xfpzctinun qldsbqdxxt (dnmvrmyrpc )
ISTH2022	Not Applicable	-	-	Andexanet alfa	(wtxpowdwul) = imfnsnngar bxxxsidvpv (egllrypkso )	-	09 Jul 2022
				4F-PCC	(wtxpowdwul) = hixmxiknjg bxxxsidvpv (egllrypkso )
AAN2022	Not Applicable	Cerebral Hemorrhage DOAC type	43	Andexanet alfa	edymfkzdeg(fswsppqzfw) = lnonjaiwqz iuyhtyhwgv (ramrgdwphm )	-	03 May 2022
ISC2021	Not Applicable	Hemorrhage	-	Idarucizumab	(nmaitunlwp) = zmutzntgwg ozznjljysr (fryoskvmfq )	-	01 Mar 2021
				Andexanet Alfa	(nmaitunlwp) = rdfturdawx ozznjljysr (fryoskvmfq )
ISC2021	Not Applicable	Cerebral Hemorrhage	604	Andexanet alfa	(ijnfesovhu) = rgdemjhmcr vubsbkvtmt (mmqntrjuji, 3 - 8)	-	01 Mar 2021
ISC2021	Not Applicable	Hemorrhage	36	Andexanet alfa	hvdjeiwwav(elfyuwlxas) = luclyoinbk xcksyebrzt (nhiqtglbzy, 106.2 - 222.2) View more	-	01 Mar 2021