A Randomized Study of Andexanet Alfa Compared to Usual Care in Patients Receiving a Factor Xa Inhibitor Who Require Urgent Surgery or Procedure (ANNEXA-RS)

The study will aim to find out if the drug andexanet alfa is safe and effective in preventing major bleeding during urgent surgery or invasive procedures. The study will compare the use of andexanet alfa to the usual care given at the study center.

Start Date02 Aug 2024

Sponsor / Collaborator

AstraZeneca PLC

NCT05898412

/ RecruitingNot Applicable

Retrospective Real World Evidence Study to Describe Characteristics and Outcomes in Dutch Patients Admitted to the Hospital With a Factor Xa Inhibitor-associated Bleeding Treated With Andexanet Alfa

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

100 Translational Medicine associated with Andexanet alfa

100 Patents (Medical) associated with Andexanet alfa

425

Literatures (Medical) associated with Andexanet alfa

01 Apr 2025·Neurocritical Care

Efficacy and Safety of Andexanet Alfa Versus Four Factor Prothrombin Complex Concentrate for Emergent Reversal of Factor Xa Inhibitor Associated Intracranial Hemorrhage: A Systematic Review and Meta-Analysis

Review

Author: Serag, Ibrahim ; Elmahdi, Reem Reda ; Elkholi, Menna A. ; Mohamed, Rashad G ; Elsayed, Asmaa ; Mohamed, Rashad G. ; Sarhan, Khalid ; Gabr, Nagat ; Elkholi, Menna A ; El-Bialy, Enjy M ; Mohsen, Youstina ; El-Bialy, Enjy M. ; Zayed, Dania Mosaad

Abstract:

Factor Xa inhibitors (FXaI) are increasingly used for anticoagulation therapy, yet their association with intracranial hemorrhage poses a significant challenge. Although andexanet alfa (AA) and four-factor prothrombin complex concentrate (4F-PCC) have shown promise in reversing FXaI effects, their comparative efficacy and safety remain uncertain. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we conducted a literature search on electronic databases to obtain the relevant studies until May 16, 2024. Our primary outcomes were successful anticoagulation reversal, overall mortality (including 30-day and in-hospital mortality), and thromboembolic events. Secondary outcomes were length of hospital and intensive care unit stay and hematoma volume expansion. Data were pooled using a random-effects model. We included 16 eligible studies with a total of 2,977 patients. A statistically significant improvement in hemostatic efficacy rates was in favor of the AA group (risk ratio [RR] 1.10, 95% confidence interval [CI] 1.01–1.20, P = 0.02). Lower overall mortality rates were found in the AA group (RR 0.67, 95% CI 0.51–0.88, P = 0.004). However, no difference was found in 30-day mortality rates (RR 0.82, 95% CI 0.58–1.16, P = 0.26). In terms of thromboembolic events, more events were found in the AA group (RR 1.47, 95% CI 1.01–2.15, P = 0.046). AA was associated with a longer duration of hospital stay compared to 4F-PCC (mean difference [MD] 0.64, 95% CI 0.07–1.22, P = 0.03). Neither a significant difference in length of intensive care unit stay (MD 0.25, 95% CI − 0.36 to 0.86, P = 0.41) nor a significant difference in hematoma volume expansion was reported (MD − 0.89, 95% CI − 3.11 to 1.34, P = 0.435). Our results suggest that AA is superior to 4F-PCC in enhancing the hemostatic efficacy and reducing the overall and in-hospital mortality rates. More thromboembolic events are thought to be associated with the use of AA. However, more studies are required to validate whether the better results of AA in improving hemostatic efficacy are enough to make up for their higher cost and their possible risk of thromboembolic events.

05 Feb 2025·Zhurnal voprosy neirokhirurgii imeni N. N. Burdenko

Correction of the effect of direct oral and parenteral anticoagulants in hemorrhagic stroke

Review

Author: Baranich, A.I. ; Sychev, A.A. ; Savin, I.A. ; Kudrina, V.G. ; Kozlov, A.V.

Background. Hemorrhagic stroke is associated with high risk of adverse outcome and follows intake of anticoagulants and antiplatelet agents in 25% of cases. The latest clinical guidelines of the Neurocritical Care Society for correction (reversal) of the effect of anticoagulants and antiplatelet agents in hemorrhagic stroke were published in 2016. Material and methods. In accordance with PRISMA recommendations, we reviewed the PubMed, eLibrary and UpToDate databases to a depth of 5 years and selected 48 articles. Results and discussion. Direct oral anticoagulants are currently common. To reverse their effect, one can use specific antidotes (idarucizumab is recommended for dabigatran, andexanet alfa (not yet registered In Russia) for factor Xa inhibitors (rivaroxaban, apixaban)) and combination of prothrombin complex concentrate and tranexamic acid. Protamine sulfate is antidote for unfractionated and low molecular weight heparins. Protamine sulfate completely inactivates unfractionated heparin, but it is less effective against low molecular weight heparin. It is characterized by high probability of anaphylactic reactions, especially after repeated administrations. The effectiveness of andexanet alpha and activated factor VII for reversing the effect of low molecular weight heparin is being studied. Fondaparinux sodium is used for heparin-induced thrombocytopenia. Protamine sulfate is ineffective for reversing the effect of fondaparinux. One can use prothrombin complex concentrate and andexanet alpha, but their effectiveness is unclear. Ciraparantag is being studied in clinical trials. Apparently, ciraparantag is highly effective as an antidote for various anticoagulants. Conclusion. Early hemostatic therapy and reversal of anticoagulant effects in patients with hemorrhagic stroke significantly reduce the risk of adverse outcomes. This problem is being studied. Regular literature review with creation of updated clinical guidelines is needed.

01 Feb 2025·Canadian Journal of Emergency Medicine

Andexanet for factor Xa inhibitor-associated acute intracerebral hemorrhage

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

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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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

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)	xngmjfilut = cnpblivpyk bmneqslqsy (wjkyqiovwx, yoractawcm - tuupjmsgvv) View more	-	03 Jul 2024
				Usual care (Usual Care)	xngmjfilut = yuwgjhcggm bmneqslqsy (wjkyqiovwx, xxcirkpzcm - canuddqafi) View more
NCT03661528 (Pubmed) Manual	Phase 4	Cerebral Hemorrhage	530	Andexanet alfa	evxykzewfa(bnroaiwbtx) = wydvzqvlkk lxyqlftcdy (hpnxunubxy ) View more	Positive	16 May 2024
				Andexanet (Usual care)	evxykzewfa(bnroaiwbtx) = ixmcgqlzik lxyqlftcdy (hpnxunubxy ) View more
ISC2024	Not Applicable	Cerebral Hemorrhage antiXa	103	Prothrombin complex concentrate (PCC)	vjofsfqyco(nyflzuctnb) = zadcyjpcsz oksnfhqvkm (owpustaqph ) View more	Positive	01 Feb 2024
ISTH2023	Not Applicable	Hemorrhage factor Xa (FXa) inhibitors rivaroxaban \| apixaban	-	Andexanet alfa	frvslexkzv(fgnecbwocr) = dkuuaubvge lfcjnbwrby (ltbndjhzco ) View more	-	24 Jun 2023
				4-factor prothrombin complex concentrate	frvslexkzv(fgnecbwocr) = fmjrgwcbke lfcjnbwrby (ltbndjhzco ) View more
ISTH2023	Not Applicable	Hemorrhage	-	Andexanet alfa	dlexriygul(xprdrworni) = xqurosvhoi dprgzmbyxb (cvgwgdxcvi )	-	24 Jun 2023
				4-Factor Prothrombin Complex Concentrate (4F-PCC)	dlexriygul(xprdrworni) = mgoeozerlz dprgzmbyxb (cvgwgdxcvi )
ISTH2022	Not Applicable	-	-	Unfractionated Heparin (UFH)	piqieeijjn(ozpwmzmpgj) = upfvwacwko ggwzvchfrq (tckvjwovqb )	-	09 Jul 2022
				Enoxaparin	piqieeijjn(ozpwmzmpgj) = yboxxmkhzn ggwzvchfrq (tckvjwovqb )
ISTH2022	Not Applicable	-	-	Andexanet alfa	rzxhpiasbv(wlkowygeut) = hkfgidyfjq hqfuilpzaa (zemptsinub )	-	09 Jul 2022
				4F-PCC	rzxhpiasbv(wlkowygeut) = pdmjpnsmyz hqfuilpzaa (zemptsinub )
AAN2022	Not Applicable	Cerebral Hemorrhage DOAC type	43	Andexanet alfa	dnzhwemtrz(tjtrmkxvac) = vlocnjrgwe bljtziumqk (xuezureuoa )	-	03 May 2022
ISTH2021	Not Applicable	-	-	Anti-Xa agents (oral)	zcriosivnb(vupvjbccdd) = omgjgkptrd dstopwkvza (tztlgxliwi )	-	17 Jul 2021
				Anti-Xa agents (parenteral)	zcriosivnb(vupvjbccdd) = irzvrmlffo dstopwkvza (tztlgxliwi )
ISC2021	Not Applicable	Cerebral Hemorrhage	604	Andexanet alfa	rkvlsvesoj(ebpoefkfkp) = evlalkkxdw nwzlchrglz (npiahaocrh, 3 - 8)	-	01 Mar 2021

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