adintrevimab (ADG20) / Invivyd, Biocon - LARVOL DELTA

EVADE: Evaluation of ADG20 for the Prevention of COVID-19 (clinicaltrials.gov) - P2/3 | N=2582 | Terminated | Sponsor: Invivyd, Inc. | N=5951 ➔ 2582

Enrollment change • Infectious Disease • Novel Coronavirus Disease

Monoclonal Antibody Therapies Against SARS-CoV-2: Promises and Realities. (PubMed, Curr Top Microbiol Immunol) - "Unfortunately, the Omicron variant of concern has completely reset all achievements so far in mAb therapy for COVID-19. Despite the intrinsic limitations of this strategy, future developments such as respiratory delivery of further engineered mAb cocktails could lead to improved outcomes."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Preliminary Results for Solid Organ Transplant Patients Enrolled in CANOPY, a Phase 3 Study to Evaluate Efficacy and Safety of VYD222, an IgG1 Monoclonal Antibody for Prevention of COVID-19 (ATC 2024) - P2/3 | "VYD222 is a re-engineered version of adintrevimab, an Fc-modified mAb that has a robust safety data package and demonstrated clinically meaningful results in Phase 2/3 clinical trials for both treatment and prevention of COVID-19 (NCT04805671, NCT04859517).* CANOPY included 2 cohorts. A single dose of VYD222 4500 mg IV was well tolerated in a subset of adult solid organ transplant recipients including those on active therapy post-transplant."

Clinical • P3 data • P3 data: top line • Back Pain • Cardiovascular • Infectious Disease • Movement Disorders • Musculoskeletal Pain • Novel Coronavirus Disease • Pain • Respiratory Diseases • Solid Organ Transplantation • Transplantation

COVID-19 update: An EUA for pemivibart (Pemgarda) for pre-exposure prophylaxis. (PubMed, Med Lett Drugs Ther) - No abstract available

Journal • Infectious Disease • Novel Coronavirus Disease

Emerging anti-spike monoclonal antibodies against SARS-CoV-2. (PubMed, Expert Opin Biol Ther) - "Strategies to potentially mitigate this are discussed. Based on prior successful experience, immunocompromised patients will certainly benefit from the utilization of mAbs for the prevention and treatment of COVID-19; thus, we need to design potential interventions to ensure the sustained activity of these agents."

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

Prevention of COVID-19 Following a Single Intramuscular Administration of Adintrevimab: Results From a Phase 2/3 Randomized, Double-Blind, Placebo-Controlled Trial (EVADE). (PubMed, Open Forum Infect Dis) - P2/3 | "A single intramuscular injection of adintrevimab provided prophylactic efficacy against COVID-19 due to susceptible variants without safety concerns. Clinical trial registration. NCT04859517."

Clinical • Journal • P2/3 data • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Efficacy and Safety of Adintrevimab (ADG20) for the Treatment of High-Risk Ambulatory Patients With Mild or Moderate Coronavirus Disease 2019: Results From a Phase 2/3, Randomized, Placebo-Controlled Trial (STAMP) Conducted During Delta Predominance and Early Emergence of Omicron. (PubMed, Open Forum Infect Dis) - P2/3 | "Clinical Trial Registration. NCT04805671."

Journal • P2/3 data • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Safety, Pharmacokinetics, Serum Neutralizing Titers, and Immunogenicity of Adintrevimab, a Monoclonal Antibody Targeting SARS-CoV-2: A Randomized, Double-Blind, Placebo-Controlled, Phase 1 Dose-escalation Study in Healthy Adults. (PubMed, Infect Dis Ther) - "Adintrevimab at doses of 300 mg IM, 500 mg IV, and 600 mg IM was well tolerated in healthy adults. Adintrevimab demonstrated dose-proportional exposure, rapid development of neutralizing antibody titers, and an extended half-life."

Clinical • Journal • P1 data • PK/PD data • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Comparative Binding Ability of Human Monoclonal Antibodies against Omicron Variants of SARS-CoV-2: An In Silico Investigation. (PubMed, Antibodies (Basel)) - "Furthermore, the cDNA of chimeric mAb was cloned in silico within pET30ax for recombinant production. In conclusion, the present study represents the candidature of human mAbs (beludavimab and adintrevimab) and the therapeutic potential of designed chimeric mAb for treating Omicron-infected patients."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Antibody-mediated protection against symptomatic COVID-19 can be achieved at low serum neutralizing titers. (PubMed, Sci Transl Med) - "Extrapolation of adintrevimab pharmacokinetic data suggests that protection against susceptible variants could be maintained for about 3 years. The results provide a benchmark for the selection of next-generation vaccine candidates and support the use of broad, long-acting monoclonal antibodies as alternatives or supplements to vaccination in high-risk populations."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Prophylactic Administration of the Monoclonal Antibody Adintrevimab Protects against SARS-CoV-2 in Hamster and Non-Human Primate Models of COVID-19. (PubMed, Antimicrob Agents Chemother) - "Adintrevimab is a human immunoglobulin G1 monoclonal antibody engineered to have broad neutralization against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants and other SARS-like coronaviruses with pandemic potential. In both Syrian golden hamster and rhesus macaque models, prophylactic administration of a single dose of adintrevimab provided protection against SARS-CoV-2/WA1/2020 infection in a dose-dependent manner, as measured by significant reductions in lung viral load and virus-induced lung pathology, and by inhibition of viral replication in the upper and lower respiratory tract."

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

EVADE: Evaluation of ADG20 for the Prevention of COVID-19 (clinicaltrials.gov) - P2/3 | N=5951 | Terminated | Sponsor: Invivyd, Inc. | Trial completion date: Mar 2023 ➔ Nov 2022 | Active, not recruiting ➔ Terminated; All primary efficacy data has been collected and analyzed. Based on the safety data gathered to date, it has been determined that continued participation by study subjects would not yield any additional beneficial safety information.

Trial completion date • Trial termination • Infectious Disease • Novel Coronavirus Disease

STAMP: Evaluation of ADG20 for the Treatment of Mild or Moderate COVID-19 (clinicaltrials.gov) - P2/3 | N=417 | Terminated | Sponsor: Invivyd, Inc. | N=1084 ➔ 417 | Trial completion date: Mar 2023 ➔ Nov 2022 | Active, not recruiting ➔ Terminated; All primary efficacy data has been collected and analyzed. Based on the safety data gathered to date, it has been determined that continued participation by study subjects would not yield any additional beneficial safety information.

Enrollment change • Trial completion date • Trial termination • Infectious Disease • Novel Coronavirus Disease

Adintrevimab (ADI) Population Pharmacokinetics (PPK) in Phase 1 and Phase 2/3 COVID-19 Prevention and Treatment Study Participants (IDWeek 2022) - No abstract available

Clinical • P1 data • P2/3 data • PK/PD data • Infectious Disease • Novel Coronavirus Disease

Integrated Quantitative Systems Pharmacology (QSP) Characterizing Viral Dynamics After Intramuscular (IM) Adintrevimab (ADI) Administration in Participants with Mild to Moderate Coronavirus Disease (COVID-19) (IDWeek 2022) - No abstract available

Infectious Disease • Novel Coronavirus Disease

Clinical and Virologic Outcomes with Early Adintrevimab (ADI) Monoclonal Antibody Therapy in Mild and Moderate COVID-19 (IDWeek 2022) - No abstract available

Clinical • Infectious Disease • Novel Coronavirus Disease

Higher Doses of Adintrevimab, an Extended Half-Life Monoclonal Antibody, for the Treatment and Prevention of COVID-19: Preliminary Results from a Phase 1 Single Ascending-Dose Study (IDWeek 2022) - No abstract available

P1 data • Infectious Disease • Novel Coronavirus Disease

A broad and potent neutralization epitope in SARS-related coronaviruses. (PubMed, Proc Natl Acad Sci U S A) - "Here, we show that therapeutic antibody ADG20 is able to neutralize SARS-CoV-2 variants of concern (VOCs) including Omicron (B.1.1.529) as well as other SARS-related coronaviruses...Importantly, antibodies that are able to target this site generally neutralize a broad range of VOCs, albeit with reduced potency against Omicron. Thus, this conserved and vulnerable site can be exploited for the design of universal vaccines and therapeutic antibodies."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Preliminary Results From The Phase 2/3 Randomized, Double-blind, Placebo-controlled Trial To Evaluate The Efficacy And Safety Of Adintrevimab In The Treatment Of Ambulatory Participants With Mild Or Moderate Covid-19 (STAMP) (ASM Microbe 2022) - "A single dose of adintrevimab 300 mg IM provided a statistically significant and clinically meaningful reduction in the risk of COVID-19 related hospitalization and all-cause death compared to placebo in high-risk ambulatory patients with mild to moderate COVID-19. Adintrevimab had a safety profile similar to that of placebo."

Clinical • P2/3 data • Immunology • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Population pharmacokinetics (PPK) of ADG20, an extended half-life monoclonal antibody being developed for the treatment and prevention of COVID-19 (ECCMID 2022) - No abstract available

Clinical • PK/PD data • Infectious Disease • Novel Coronavirus Disease

ADG20, a half-life–extended monoclonal antibody in development for the prevention and treatment of COVID-19, demonstrates potent neutralisation against SARS-CoV-2 variants (ECCMID 2022) - No abstract available

Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Adagio Therapeutics Provides Update on Timing of Adintrevimab EUA Request (GlobeNewswire) - "The Omicron BA.2 variant, which has shown reduced in vitro susceptibility to monoclonal antibodies, has recently emerged as the current predominant variant of SARS-CoV-2 in the U.S. Adintrevimab....Based on feedback from the U.S. Food and Drug Administration (FDA) regarding adintrevimab’s lack of neutralizing activity against the BA.2 variant, Adagio is pausing the submission of an EUA request. Adagio intends to continue engaging with the FDA and monitor the evolution of SARS-CoV-2 and the in vitro activity of adintrevimab against predominant variants in the U.S. to determine the optimal timing for its planned EUA request....Adagio is on-track to have more than one million doses of adintrevimab secured in 2022, in preparation of its potential utility as a prophylaxis and treatment option for COVID-19 in the future."

Commercial • FDA event • Infectious Disease • Novel Coronavirus Disease

Why Adagio Therapeutics Stock Is Soaring Today (Business Insider) - "Adagio Therapeutics...is trading higher Wednesday after the company announced its investigational drug adintrevimab (ADG20) was the first monoclonal antibody to meet primary endpoints with statistical significance across pre- and post-exposure prophylaxis and treatment for COVID-19. The company plans to seek U.S. Emergency Use Authorization....The stock was up 39.5% at $5.39 at time of publication..."

P2/3 data • Stock price • Infectious Disease • Novel Coronavirus Disease

Adagio Therapeutics Announces ADG20 (adintrevimab) is the First Monoclonal Antibody to Meet Primary Endpoints with Statistical Significance Across Pre- and Post-exposure Prophylaxis and Treatment for COVID-19 and Plans to Seek U.S. Emergency Use Authorization (GlobeNewswire) - P2/3 | N=6,412 | EVADE (NCT04859517) | N=1,084 | STAMP (NCT04805671) | Sponsor: Adagio Therapeutics, Inc. | "...Adagio plans to engage with the U.S. Food and Drug Administration (FDA) and to submit an Emergency Use Authorization (EUA) application in the second quarter of 2022 for adintrevimab for both the prevention and treatment of COVID-19....In the primary efficacy analysis in the PEP cohort, adintrevimab met statistical significance and was associated with a lower incidence of symptomatic COVID-19 through day 28 compared with placebo (3/173, 1.7% vs. 12/175, 6.9%, respectively)....demonstrating a 75% relative risk reduction in favor of adintrevimab through 28 days....Adintrevimab was associated with a statistically significant lower incidence of COVID-19 related hospitalization or all cause death through day 29 compared with placebo (8/169, 4.7% vs. 23/167, 13.8%)...demonstrating a 66% relative risk reduction in favor of adintrevimab."

FDA event • P2/3 data • Infectious Disease • Novel Coronavirus Disease

Insights on the mutational landscape of the SARS-CoV-2 Omicron variant receptor-binding domain. (PubMed, Cell Rep Med) - "Since our initial modeling following the identification of Omicron, these predictions have been realized by experimental findings of Omicron neutralization escape from therapeutic antibodies ADG20, AZD8895, and AZD1061. Importantly, the AAI predicted escape resulting from indirect epitope perturbations was not captured by previous sequence or point mutation analyses. Finally, for several Omicron RBD mutations, we find evidence for a plausible role in enhanced transmissibility via disruption of RBD-down conformational stability at the RBD-RBD interface."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases