Delving into the Latest Updates on Tixagevimab with Synapse

Overview

Basic Info

Drug Type

Monoclonal antibody

Synonyms

AZD 8895, AZD-8895, AZD8895

Target

SARS-CoV-2 S protein

Mechanism

SARS-CoV-2 S protein inhibitors(Coronavirus spike glycoprotein inhibitors)

Therapeutic Areas-

Active Indication-

Inactive Indication-

Originator Organization

AstraZeneca PLC

Active Organization-

Inactive Organization-

Drug Highest Phase-

First Approval Date-

Regulation-

Gene Sequence

Sequence Code 616721365H

Source: *****

Sequence Code 616721366L

Source: *****

The study aims at assessing the non-inferiority of tixagevimab plus cilgavimab and nirmatrelvir plus ritornavir vs. sotrovimab (reference standard due to the wider evidence gathered on its efficacy) on COVID-19 progression in a real-life setting of outpatients aged at least 50 years at an early stage of the disease. The progression of COVID-19 disease (hospitalization, need for supplementary oxygen therapy at home, death) within 14 days of randomisation is the composite outcome variable on which the calculation of the sample size is based. Based on available data regarding the reduction in the number of hospitalisations and medical visits with the use of sotrovimab at an early-stage of COVID-19, a disease progression of 1% has been estimated in the reference arm. 3% delta margin was considered clinically relevant, taking into account both the estimates of disease progression in the study population in absence of early treatment (7%, based on national data) and the efficacy of the reference standard. Therefore, 1095 participants will be randomly assigned in an equal ratio between the reference standard and each of the other two experimental arms (1:1:1). Randomization will be computer-generated in permuted blocks with a stratification based on site.

Start Date07 Mar 2022

Sponsor / Collaborator

Azienda Ospedaliera Universitaria Integrata Verona

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100 Clinical Results associated with Tixagevimab

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100 Translational Medicine associated with Tixagevimab

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100 Patents (Medical) associated with Tixagevimab

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203

Literatures (Medical) associated with Tixagevimab

01 Jan 2024·Cancer

Efficacy and safety of tixagevimab‐cilgavimab versus SARS‐CoV‐2 breakthrough infection in the hematological conditions

Article

Author: Leotta, Salvatore ; Del Fabro, Vittorio ; Nardo, Antonella ; Orofino, Alessandra ; Parisi, Marina S ; Romano, Alessandra ; Palumbo, Giuseppe A ; Cupri, Alessandra ; Di Raimondo, Francesco ; Giunta, Giuliana ; Cambria, Daniela ; Conticello, Concetta ; Duminuco, Andrea ; Figuera, Amalia ; Chiarenza, Annalisa ; Milone, Giuseppe

Abstract:

Background:

Managing SARS‐CoV‐2 infection in frail and immunosuppressed patients still represents an open challenge, but, starting from the phase 3 PROVENT study, prophylaxis with tixagevimab‐cilgavimab has improved the approach in this category of patients, guaranteeing a better outcome and inferior mortality. Real‐life data in a heterogeneous cohort are few.

Methods:

The aim of this study is to evaluate the benefit of prophylaxis with tixagevimab‐cilgavimab in a cohort of 202 patients affected by different hematological diseases (lymphoproliferative, myeloproliferative, autoimmune, patients recently receiving a bone marrow transplant), active (with ongoing treatment), or in watch‐and‐wait strategy, followed in our center, during a median follow‐up of 249 (45‐325) days.

Results:

An incidence of 44 breakthrough infections (21.8%) is reported, with no treatment‐related adverse effects. Age ≥70 years, ongoing treatment (above all with monoclonal antibodies), baseline lymphoproliferative disorders, and prior virus exposure are identified as risk factors related to subsequent infection (p < 0.05). Moreover, the incidence is higher in low/nonresponse to prior vaccination (p = .002). Patients treated with tixagevimab‐cilgavimab had a mild course of the infection and a reduction of the duration compared with preprophylaxis infection (11 vs. 15 days, p < .001). The concurrent treatment with anti‐CD20 monoclonal antibodies and B–non‐Hodgkin lymphoma still confers a higher duration of infection despite prophylaxis. No deaths attributable to the infection occurred.

Conclusion:

Prophylaxis treatment seems to be a valid and safe strategy, although not preventing breakthrough infection, but the severe complications associated with the infection and the possible delays in administering lifesaving therapies from long positivity.

31 Dec 2023·mAbs

Developability profiling of a panel of Fc engineered SARS-CoV-2 neutralizing antibodies

Article

Author: Gallegos, Austin ; Garcia, Andrew ; Shandilya, Harini ; Dippel, Andrew ; Machiesky, LeeAnn ; Christian, Elizabeth ; Chen, Xiaoru ; Esser, Mark T. ; Barnes, Arnita ; Liu, Weiyi ; Rajan, Sarav ; Prophet, Meagan ; Rosenthal, Kim ; Kallewaard, Nicole L. ; Mody, Neil ; Xu, Weichen ; Kaplan, Gilad ; Parupudi, Arun ; Wons, Kevin ; Rickert, Keith ; Damschroder, Melissa ; Ren, Song ; Delmar, Jared ; Li, Qing ; Lin, Jia ; Esfandiary, Reza ; Du, Qun ; Farmer, Erika ; Varkey, Reena ; Wu, Yuling ; Loo, Yueh-Ming ; Aleti, Vineela

To combat the COVID-19 pandemic, potential therapies have been developed and moved into clinical trials at an unprecedented pace. Some of the most promising therapies are neutralizing antibodies against SARS-CoV-2. In order to maximize the therapeutic effectiveness of such neutralizing antibodies, Fc engineering to modulate effector functions and to extend half-life is desirable. However, it is critical that Fc engineering does not negatively impact the developability properties of the antibodies, as these properties play a key role in ensuring rapid development, successful manufacturing, and improved overall chances of clinical success. In this study, we describe the biophysical characterization of a panel of Fc engineered ("TM-YTE") SARS-CoV-2 neutralizing antibodies, the same Fc modifications as those found in AstraZeneca's Evusheld (AZD7442; tixagevimab and cilgavimab), in which the TM modification (L234F/L235E/P331S) reduce binding to FcγR and C1q and the YTE modification (M252Y/S254T/T256E) extends serum half-life. We have previously shown that combining both the TM and YTE Fc modifications can reduce the thermal stability of the CH2 domain and possibly lead to developability challenges. Here we show, using a diverse panel of TM-YTE SARS-CoV-2 neutralizing antibodies, that despite lowering the thermal stability of the Fc CH2 domain, the TM-YTE platform does not have any inherent developability liabilities and shows an in vivo pharmacokinetic profile in human FcRn transgenic mice similar to the well-characterized YTE platform. The TM-YTE is therefore a developable, effector function reduced, half-life extended antibody platform.

23

News (Medical) associated with Tixagevimab

16 May 2024

·firstwordpharma.com

AstraZeneca touts enhanced protection with COVID-19 antibody in immunocompromised people

AstraZeneca on Thursday said the long-acting antibody sipavibart significantly reduced the incidence of symptomatic COVID-19 compared with placebo or its predecessor antibody cocktail Evusheld (tixagevimab/cilgavimab) in a Phase III pre-exposure prophylaxis study involving immunocompromised individuals — a population that accounts for nearly a quarter of cases with worse outcomes.With the positive readout, Astrazeneca is poised to compete against Invivyd's Pemgarda (pemivibart), which recently secured an emergency-use authorisation (EUA) in the US for pre-exposure COVID-19 prophylaxis of immunocompromised patients.“Immunocompromised patients currently have limited or no options for COVID-19 protection…despite often being fully vaccinated,” noted Iskra Reic, EVP of vaccines and immune therapies at AstraZeneca, adding that “sipavibart has the potential to prevent COVID-19” in this vulnerable population.The SUPERNOVA trial randomised 3335 immunocompromised participants to receive either a single 300mg intramuscular dose of sipavibart or a comparator consisting of placebo or Evusheld. The participants included individuals aged 12 years and above, at risk of not adequately responding to active immunisation and at high risk for developing severe COVID-19.Superior protection across variantsTop-line results showed sipavibart met the study’s dual primary endpoints — reducing the risk of symptomatic disease from any SARS-CoV-2 variant and the risk of infections from variants not harbouring the F456L mutation, relative to the comparator. AstraZeneca noted that the protection offered by sipavibart was consistent across the evolving variant landscape throughout the study.In terms of safety, the antibody was well tolerated, with a comparable adverse-event profile between the sipavibart and control arms. Detailed findings will be unveiled at a forthcoming medical conference.AstraZeneca’s Evusheld lost its EUA for pre-exposure prophylaxis in the US early last year, after failing to neutralise circulating SARS-CoV-2 variants in vitro. The drugmaker now intends to engage with regulators to outline the approval process for sipavibart, looking to regain its position in the COVID-19 prophylactics market.

Clinical ResultPhase 3Emergency Use Authorization

22 Mar 2024

·firstwordpharma.com

US okays Invivyd's Pemgarda to guard immunocompromised against COVID

The FDA has issued an emergency-use authorisation (EUA) for Invivyd's monoclonal antibody Pemgarda (pemivibart/VYD222) as pre-exposure prophylaxis against COVID-19 in certain adults and adolescents with moderate-to-severe immune compromise.The green light offers a new preventive option for at-risk populations following the removal of AstraZeneca's Evusheld (tixagevimab co-packaged with cilgavimab) from the US market early last year due to its lack of effectiveness against Omicron subvariants."Pemgarda's authorisation… marks strategic proof-of-concept for our platform approach designed to enable rapid, serial generation of durable antibodies targeting conserved viral epitopes," said CEO Dave Hering.Invivyd said the EUA is based on positive immunobridging data from the ongoing Phase III CANOPY trial, as well as data showing that serum neutralising antibody titers against JN.1 were consistent with the titers levels linked to protection in prior clinical trials of adintrevimab (ADG20), which is the parent mAb for Pemgarda. JN.1 is currently the dominant variant circulating in the US according to estimates from the US Centers for Disease Control and Prevention (CDC).More to follow.

Phase 3ImmunotherapyEmergency Use AuthorizationClinical Result

10 Apr 2023

·www.pharmaceutical-technology.com

Malaysia approves additional indication for Astrazeneca’s Evusheld

Astrazeneca’s Evusheld will be used to treat people who may not have an adequate immune response to Covid-19 vaccination. Credit: Hakan Nural on Unsplash. The Malaysian Ministry of Health (MoH) has reportedly approved additional indication of Astrazeneca ’s Evusheld 100mg/ml solution for injection (Tixagevimab 100mg/ml and Cilgavimab 100mg/ml) for Covid-19 prevention. Health director-general Tan Sri Dr Noor Hisham Abdullah stated that the approval of Evusheld was granted at the 383rd Drug Control Authority (DCA) meeting. The approval comes after the therapy was granted conditional registration approval during the 372nd DCA meeting. The MoH noted that Evusheld’s conditional approval status will remain, while the latest approval is related to additional indications to treat Covid-19. The therapy is intended to prevent Covid-19 in adult and adolescent patients aged 12 years and above, who do not need additional oxygen support and are at high risk of the infection becoming more severe. It will also be used for the treatment of people who are not likely to have an adequate immune response to Covid-19 vaccination or for people who are not recommended for Covid-19 vaccination. Dr Noor Hisham was quoted as saying: “The use of Evusheld was based on clinical guidelines issued by the health ministry.” Evusheld (formerly AZD7442) is a combination of two long-acting antibodies, tixagevimab (AZD8895) and cilgavimab (AZD1061). The long-acting antibodies are obtained from B-cells that are donated by convalescent patients following Covid-19 infection. In September last year, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) recommended marketing authorisation for Evusheld for the treatment of Covid-19.

Drug Approval

100 Deals associated with Tixagevimab

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R&D Status

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


IMS2023	Not Applicable	Multiple Myeloma	55	Tixagevimab/cilgavimab (Evusheld)	bafjgsxrqz(ahvjqcveuj) = Overall, 5 patients (9%) were diagnosed with COVID-19 at a median of 1 month (range 1-2) after receiving tixagevimab/cilgavimab. All of these patients received nirmatrelvir/ritonavir (Paxlovid) for 5 days as outpatients along with supportive care as per standard clinical practice and recovered completely. There were no COVID-19-related hospitalization or deaths. qyszokrktb (otechjwoxi ) View more	-	26 Sep 2023
IMS2023	Not Applicable	Multiple Myeloma	44	Tixagevimab/cilgavimab	yixwwovitn(pgafdabeoy) = xrvyqosezn aotmvcplca (bvykhvuqmc )	-	26 Sep 2023
EULAR2023	Not Applicable	Collagen Diseases	21	Tixagevimab and Cilgavimab (TGM/CGM)	gyyougyytn(kqktiqwjpk) = no COVID-19 related symptoms were observed in the month of follow-up after TGM/CGM administration cmezowlvod (shjfhliaoj ) View more	-	31 May 2023
ACTRIMS2023	Not Applicable	Multiple Sclerosis	-	Tixagevimab/Cilgavimab	wwfcrdxsij(lgzeuliveq) = Breakthrough infections on tixagevimab/cilgavimab occurred in 4 cases (8%), 3 of which occurred in patients receiving medications suppressing B and T lymphocyte proliferation (two cases on mycophenolate mofetil, and one case with prior history of cyclophosphamide and mitoxantrone treatment) hmyxzkqdju (equbfnbues )	-	30 May 2023
ACTRIMS2023	Not Applicable	Multiple Sclerosis	-	No Tixagevimab/Cilgavimab		-	30 May 2023
S31.010 (AAN2023)	Not Applicable	Multiple Sclerosis	348	Tixagevimab/cilgavimab	lozkgeldod(xqckehqyxg) = 3 of which occurred in patients receiving medications suppressing B and T lymphocyte proliferation (two cases on mycophenolate mofetil, and one case with prior history of cyclophosphamide and mitoxantrone treatment) vmsxoqnmdt (fbsffzxwzd )	-	25 Apr 2023
P376 (EBMT2023)	Not Applicable	-	-	CAR-T-cell recipients	jxzuslpvgz(jgvvgskocj) = No patients reported adverse events from drug administration lrrsqhafys (bvrqskftkt )	-	23 Apr 2023
P376 (EBMT2023)	Not Applicable	-	-	HSCT recipients		-	23 Apr 2023