Kavigale (sipavibart) / AstraZeneca, RQ Bio - LARVOL DELTA

Sipavibart (AZD-3152), a COVID-19 Pre-Exposure Prophylaxis in Myeloma Treated with BCMA/CD3 Bispecific Antibodies (ASH 2024) - P2/3 | "Thirteen (68%) were treated with Elranatamab, 6 (32%) were treated with Teclistamab and 4 (21%) had an anti CD38 monoclonal antibody in combination with the BCMA/CD3 BsAbs. Sipavibart is well tolerated and appears effective in PreP treatment in MM treated with BCMA/CD3 BsAb, patients that are severely immunocompromised. This data needs confirmation in larger study of these MM patients who are severely immunocompromised and at high-risk of severe COVID-19 infections."

Cardiovascular • Chronic Kidney Disease • Diabetes • Genetic Disorders • Hematological Malignancies • Infectious Disease • Metabolic Disorders • Multiple Myeloma • Nephrology • Obesity • Oncology • Renal Disease • Respiratory Diseases • CD4 • CD8

Toward a Brighter Future for Preventing COVID-19 in Patients With Hematologic Malignancies: Leveraging the Power of Current Strategies and Next-Generation Agents (ASH 2023) - "Tixagevimab/cilgavimab lost its emergency use authorization as prevention for immunocompromised patients because of its lack of efficacy against newer variants. However, next-generation prevention agents are in development, including a new monoclonal antibody, AZD3152...PeerView's expert faculty will discuss strategies to engage patients with elevated risk of serious COVID-19 infection in the development of customized prevention plans. In addition, they will explore approaches to overcoming real-time barriers to access and use of available options for prevention of serious COVID-19 illness."

Clinical • Hematological Malignancies • Infectious Disease • Novel Coronavirus Disease • Oncology

A SARS-CoV-2 variant‑adjusted threshold of protection model for monoclonal antibody pre-exposure prophylaxis against COVID-19. (PubMed, Nat Commun) - P2/3, P3 | "Using efficacy data from the phase 3 PROVENT pre-exposure prophylaxis trial of tixagevimab-cilgavimab (NCT04625725), individual nAb ID50 titres were predicted by dividing serum mAb concentration by prevalence-adjusted tixagevimab-cilgavimab potency (from in vitro IC50 values combined with viral surveillance data) and related to efficacy with a Cox model. The Threshold of Protection (ToP) Cox model was externally validated using data from the phase 3 SUPERNOVA trial (NCT05648110), which assessed sipavibart efficacy against symptomatic COVID-19 in immunocompromised participants. The PROVENT ToP model estimated the variant-specific observed efficacies from SUPERNOVA for 3 and 6 months post any dose with Lin's concordance of 0.86 and 0.75, respectively. This approach integrates predicted nAb ID50 titres against multiple SARS-CoV-2 variants into a ToP model that can be applied across different variants and could serve as a surrogate endpoint in immunobridging..."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

SARS-CoV-2 Specific Monoclonal Antibody for Post-COVID-19 Conditions (Long COVID) (clinicaltrials.gov) - P2 | N=100 | Recruiting | Sponsor: Nancy Klimas | Not yet recruiting ➔ Recruiting

Enrollment open • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Sipavibart: First Approval. (PubMed, Drugs) - "Sipavibart was also approved in the EU for the pre-exposure prophylaxis of COVID-19 in adults and adolescents aged ≥ 12 years weighing ≥ 40 kg who are immunocompromised due to a medical condition or receipt of immunosuppressive treatments in January 2025 and in Canada in March 2025. This article summarizes the milestones in the development of sipavibart leading to this first approval for the pre-exposure prophylaxis of COVID-19 in immunocompromised adults and adolescents."

Journal • Review • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Potential use of the SARS-CoV-2 monoclonal antibody sipavibart in people with multiple sclerosis: definition of different patient archetypes from an Italian expert group perspective. (PubMed, J Neurol) - "Subjects with general or disease specific risk factors for severe infections, patients treated with S1P receptor modulators, anti-CD20 agents, alemtuzumab or cladribine, pediatric patients, and pregnant women with MS could represent the ideal candidates for PrEP with sipavibart."

Journal • Review • CNS Disorders • Infectious Disease • Multiple Sclerosis • Neuromyelitis Optica Spectrum Disorder • Novel Coronavirus Disease • Pediatrics • Rare Diseases • Respiratory Diseases

Dynamics of SARS-CoV-2 variants and mutations in Central Sweden between 2023 and 2024 and their potential implications on monoclonal antibodies pemivibart and sipavibart as PrEP in the region. (PubMed, Infect Dis (Lond)) - "The use of sipavibart or pemivibart as PrEP for COVID-19 in the region may currently not be effective unless new SARS-CoV-2 variants appear not containing these resistance mutations. Further, new mAbs under development as PrEP for COVID-19 can be effectively used by routinely sequencing SARS-CoV-2 in patients to identify variants and resistance mutations."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Preemptive optimization of a clinical antibody for broad neutralization of SARS-CoV-2 variants and robustness against viral escape. (PubMed, Sci Adv) - "Our top candidate, 3152-1142, restores full potency (100-fold improvement) against the more recently emerged XBB.1.5+F456L variant that escaped AZD3152, maintains potency against previous variants of concern, and shows no additional vulnerability as assessed by DMS. This preemptive mitigation demonstrates a generalizable approach for optimizing existing antibodies against potential future viral escape."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Optimized ACE2-Fc With Picomolar Pan-Neutralization of SARS-CoV-2 Variants, Including JN.1 and KP.2 (CROI 2025) - "Using pseudovirus and full virus-based neutralization assays, all candidates were functionally validated and compared to the monoclonal antibody Sipavibart (AZD3152), against a large panel of pre-Omicron and Omicron-derived variants, including JN.1 and KP.2...While the development and validation of traditional monoclonal antibodies is long and costly. ACE2-Fc molecules could provide an off-the-shelf solution ready to protect the immunocompromised and other risk groups against the rapidly evolving SARS-CoV-2 variants and any coronaviruses using ACE2 as receptor."

Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases • Targeted Protein Degradation • ACE2

Study Understanding Pre-Exposure pRophylaxis of NOVel Antibodies (SUPERNOVA) Sub-study: Study Understanding Pre-Exposure pRophylaxis of NOVel Antibodies (SUPERNOVA) Sub-study (clinicaltrials.gov) - P2/3 | N=3882 | Completed | Sponsor: AstraZeneca | Active, not recruiting ➔ Completed

Trial completion • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases • CD4

Sipavibart: when a success changes into a failure. (PubMed, Lancet Infect Dis) - No abstract available

Journal

Efficacy and safety of sipavibart for prevention of COVID-19 in individuals who are immunocompromised (SUPERNOVA): a randomised, controlled, double-blind, phase 3 trial. (PubMed, Lancet Infect Dis) - P2/3 | "The primary analysis showed efficacy and safety of sipavibart in preventing symptomatic COVID-19 in participants who are immunocompromised when susceptible (ie, non-Phe456Leu-containing) variants dominated, although no efficacy was shown against resistant (ie, Phe456Leu-containing) variants that dominate as of November, 2024."

Journal • P3 data • Cardiovascular • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

RQ Bio welcomes positive CHMP opinion on Kavigale for prevention of COVID-19 in immunocompromised individuals (GlobeNewswire) - "RQ Biotechnology Ltd....today welcomes the decision by the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) to recommend the granting of marketing authorisation for the medicinal product Kavigale. Kavigale is intended for the prevention of COVID-19 in immunocompromised individuals- aged 12 years and older and was reviewed under the EMA’s accelerated assessment programme."

CHMP • Novel Coronavirus Disease

Study of AZD3152 Intramuscular Injection or Intravenous Infusion in Healthy Japanese Adult Participants (clinicaltrials.gov) - P1 | N=24 | Completed | Sponsor: AstraZeneca | Active, not recruiting ➔ Completed

Trial completion • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Escape of SARS-CoV-2 Variants KP.1.1, LB.1, and KP3.3 From Approved Monoclonal Antibodies. (PubMed, Pathog Immun) - "AZD3152/Sipavibart neutralized JN.1.1 but lost antiviral efficacy against KP.1.1, LB.1, and KP3.3. Our results highlight the need for a close clinical monitoring of VYD222/Pemivibart and raise concerns about the clinical efficacy of AZD3152/Sipavibart."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Characteristics of the first immunocompromised patients to receive Sipavibart as an early access treatment for COVID-19 pre-exposure prophylaxis in France (IDWeek 2024) - No abstract available

Clinical • Infectious Disease • Novel Coronavirus Disease

Dose Exploration Intramuscular/Intravenous Prophylaxis Pharmacokinetic Exposure Response Study (clinicaltrials.gov) - P1 | N=98 | Completed | Sponsor: AstraZeneca | Active, not recruiting ➔ Completed

Trial completion • Infectious Disease • Novel Coronavirus Disease

Characteristics of the first immunocompromised patients to receive sipavibart as an early access treatment for COVID-19 pre-exposure prophylaxis in France. (PubMed, Hum Vaccin Immunother) - "The first patients to receive Sipavibart had different profiles, but they were all highly immunocompromised with frequently associated hypogammaglobulinemia and other chronic conditions. No adverse event was reported."

Journal • Infectious Disease • Novel Coronavirus Disease

AZD3152 neutralizes SARS-CoV-2 historical and contemporary variants and is protective in hamsters and well tolerated in adults. (PubMed, Sci Transl Med) - P2/3 | "In the phase 1 sentinel safety cohort of the ongoing SUPERNOVA study (ClinicalTrials.gov: NCT05648110), a single 600-mg intramuscular injection of AZD5156 (containing 300 mg each of AZD3152 and cilgavimab) was well tolerated in adults through day 91. Observed serum concentrations of AZD3152 through day 91 were similar to those observed with cilgavimab and consistent with predictions for AZD7442, a SARS-CoV-2-neutralizing antibody combination of cilgavimab and tixagevimab, in a population pharmacokinetic model. On the basis of its pharmacokinetic characteristics, AZD3152 is predicted to provide durable protection against symptomatic coronavirus disease 2019 caused by susceptible SARS-CoV-2 variants, such as JN.1, in humans."

Journal • Infectious Disease • Inflammation • Novel Coronavirus Disease • Respiratory Diseases

Sipavibart EMA regulatory submission accepted under accelerated assessment for COVID-19 prevention (AstraZeneca Press Release) - "AstraZeneca’s Marketing Authorisation Application (MAA) for sipavibart has been accepted under an accelerated assessment procedure by the European Medicines Agency (EMA), for the pre-exposure prophylaxis (prevention) of COVID-19 in immunocompromised patients...The MAA is based on positive results from the SUPERNOVA Phase III trial which demonstrated sipavibart’s safety and efficacy in preventing symptomatic COVID-19 in immunocompromised patients, compared to control, in a variant landscape in which COVID-19 cases captured over the course of the trial were caused by several different SARS-CoV-2 variants."

EMA filing • Infectious Disease • Novel Coronavirus Disease

Study Understanding Pre-Exposure pRophylaxis of NOVel Antibodies (SUPERNOVA) Sub-study: Study Understanding Pre-Exposure pRophylaxis of NOVel Antibodies (SUPERNOVA) Sub-study (clinicaltrials.gov) - P2/3 | N=3882 | Active, not recruiting | Sponsor: AstraZeneca | Trial primary completion date: Sep 2023 ➔ Mar 2024

Trial primary completion date • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases • CD4

NOVELLA: Study Will Assess the Safety, Neutralizing Activity and Efficacy of AZD3152 in Adults With Conditions Increasing Risk of Inadequate Protective Immune Response After Vaccination and Thus Are at High Risk of Developing Severe COVID-19 (clinicaltrials.gov) - P2 | N=116 | Completed | Sponsor: AstraZeneca | Active, not recruiting ➔ Completed

Trial completion • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

An update on the anti-Spike monoclonal antibody pipeline for SARS-CoV-2. (PubMed, Clin Microbiol Infect) - "The anti-Spike monoclonal antibody clinical pipeline is currently limited to few agents (most being single antibodies) with unknown efficacy against the dominant JN.1 sublineage. The field of antibody-based therapies requires boosting by both manufacturers and institutions."

Journal • Review • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Pharmacokinetics and safety of the SARS-CoV-2 monoclonal antibody AZD3152 are consistent with those of tixagevimab/cilgavimab (ECCMID 2024) - No abstract available

Clinical • Late-breaking abstract • PK/PD data • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Sentinel cohort safety of AZD5156/AZD3152 from the phase 1/3 SUPERNOVA trial for COVID-19 prevention in participants with immune impairment (ECCMID 2024) - No abstract available

Clinical • P1 data • Infectious Disease • Novel Coronavirus Disease