ensovibep (MP0420) / AGC Biologics, Molecular Partners, Novartis - LARVOL DELTA

Long-term outcomes of passive immunotherapy for COVID-19: A pooled analysis of a large multinational platform randomized clinical trial. (PubMed, Clin Microbiol Infect) - P3 | "In our large study of long half-life passive immunotherapy for hospitalized patients with COVID-19, we did not find evidence of a long-term effect on either mortality or rehospitalization."

Clinical • Journal • Retrospective data • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

The Designed Ankyrin Repeat Protein Antiviral Ensovibep for Nonhospitalized Patients With Coronavirus Disease 2019: Results From EMPATHY, a Randomized, Placebo-Controlled Phase 2 Study. (PubMed, Open Forum Infect Dis) - P2/3 | "Two deaths were reported with placebo and none with ensovibep. All 3 doses of ensovibep showed antiviral efficacy and clinical benefits versus placebo and an acceptable safety profile in nonhospitalized patients with COVID-19."

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

Viral Kinetics Model of SARS-CoV-2 Infection Informs Drug Discovery, Clinical Dose, and Regimen Selection. (PubMed, Clin Pharmacol Ther) - "We found good agreement between model predictions and clinical viral load reduction observed with anti-replicative nirmatrelvir/ritonavir (Paxlovid®) and neutralizing biologics bamlanivimab and casirivimab/imdevimab (REGEN-COV®), building confidence in the modeling framework to inform a dose selection...By benchmarking to bamlanivimab predictions, we justified dose levels of 75, 225, and 600 mg ensovibep to be administered intravenously in a Phase 2 clinical investigation. Upon trial completion, we found model predictions to be in good agreement with the observed patient data. These results demonstrate the utility of this modeling framework to guide the development of novel antiviral therapeutics."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

MP0420 for Inpatients With COVID-19 (An ACTIV-3/TICO Treatment Trial) (clinicaltrials.gov) - P3 | N=485 | Completed | Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) | Active, not recruiting ➔ Completed

Trial completion • Infectious Disease • Novel Coronavirus Disease

TICO: ACTIV-3: Therapeutics for Inpatients With COVID-19 (clinicaltrials.gov) - P3 | N=2753 | Completed | Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) | Active, not recruiting ➔ Completed

Trial completion • Infectious Disease • Novel Coronavirus Disease

Ensovibep, a SARS-CoV-2 antiviral DARPin, is safe and well tolerated in healthy volunteers: results of a first-in-human, ascending single-dose Phase 1 study. (PubMed, Br J Clin Pharmacol) - "Ensovibep proved safe in this first-in-human safety study and exhibited pharmacokinetic and pharmacodynamic parameters consistent with the expected treatment period required for acute COVID-19 infection."

Journal • P1 data • Immunology • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases • Vasculitis

MP0420 for Inpatients With COVID-19 (An ACTIV-3/TICO Treatment Trial) (clinicaltrials.gov) - P3 | N=496 | Active, not recruiting | Sponsor: University of Minnesota

New P3 trial • Infectious Disease • Novel Coronavirus Disease

Efficacy and Safety of Ensovibep for Adults Hospitalized With COVID-19. (PubMed, Ann Intern Med) - No abstract available

Journal • Infectious Disease • Novel Coronavirus Disease

Efficacy and Safety of Ensovibep for Adults Hospitalized With COVID-19. (PubMed, Ann Intern Med) - No abstract available

Journal • Infectious Disease • Novel Coronavirus Disease

Efficacy and Safety of Ensovibep for Adults Hospitalized With COVID-19 : A Randomized Controlled Trial. (PubMed, Ann Intern Med) - P3 | "Compared with placebo, ensovibep did not improve clinical outcomes for hospitalized participants with COVID-19 receiving standard care, including remdesivir; no safety concerns were identified. National Institutes of Health."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Viral clearance, pharmacokinetics and tolerability of ensovibep in patients with mild to moderate COVID-19 - a phase 2a, open-label, single dose escalation study. (PubMed, Br J Clin Pharmacol) - "Single-dose intravenous administration of 225 and 600 mg ensovibep appeared safe and well tolerated in patients with mild-to-moderate COVID-19. Ensovibep showed favourable pharmacokinetics in patients and the pharmacodynamic results warrant further research in a larger phase 2/3 randomized-controlled trail."

Journal • P2a data • PK/PD data • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

CLINICAL AND VIROLOGIC EFFICACY OF MP0420, A DARPIN THERAPEUTIC, IN AMBULATORY PATIENTS WITH COVID-19: RESULTS FROM THE PHASE 2 PLACEBO-CONTROLLED EMPATHY STUDY (CHEST 2022) - No abstract available

Clinical • P2 data • Infectious Disease • Novel Coronavirus Disease

Ensovibep antiviral activity in ambulatory patients with COVID-19 is independent of baseline anti-SARS-CoV-2 antibodies and exhibits minimal selective pressure – Results from the placebo-controlled EMPATHY trial (IDWeek 2022) - No abstract available

Clinical • Infectious Disease • Novel Coronavirus Disease

Faster clinical recovery with ensovibep compared to placebo in patients with mild-to-moderate COVID-19: interim results from the EMPATHY Phase 2 trial (ERS 2022) - P2/3 | "The cumulative proportion of patients with sustained clinical recovery by Day 15 were 44%, 54%, 55% and 36% in 600mg, 225mg, 75mg, and placebo arms, respectively. Conclusions Ensovibep administration was associated with earlier sustained clinical recovery versus placebo."

Clinical • P2 data • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Current and future therapeutic options for COVID-19 (PubMed, Ned Tijdschr Geneeskd) - "The anti-inflammatory agents dexamethasone (corticosteroid), and tocilizumab and sarilumab (IL6-inhibitors) are effective in the treatment of late COVID-19. Other anti-inflammatory agents, like anakinra (IL1-inhibitor), baricitinib and tofacitinib (JAK-inhibitors) and lenzilumab (GM-CSF-inhibitor) have also shown positive results in late COVID-19...Virus-inhibitors, like remdesivir, molnupiravir and nirmatrelvir/ritonavir decrease the risk of hospitalization and the development of severe COVID-19 by patients with early symptoms. Monoclonal antibodies have shown limited or no efficacy against the omicron-variant of SARS-CoV-2. Fluvoxamine, l-arginine, AT-527 and ensovibep are considered as potential promising new therapies for the treatment of early COVID-19."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases • CSF2

"What about ensovibep? Its a shame how fda acts to protect pfizers interests" (@Mex37553606)

TICO: ACTIV-3: Therapeutics for Inpatients With COVID-19 (clinicaltrials.gov) - P3 | N=2753 | Active, not recruiting | Sponsor: University of Minnesota | N=10000 ➔ 2753

Enrollment change • Infectious Disease • Novel Coronavirus Disease

"Do you still see a chance for ensovibep?" (@Mex37553606)

TICO: ACTIV-3: Therapeutics for Inpatients With COVID-19 (clinicaltrials.gov) - P3 | N=10000 | Active, not recruiting | Sponsor: University of Minnesota | Trial completion date: Jul 2022 ➔ Jul 2023

Trial completion date • Infectious Disease • Novel Coronavirus Disease

"Corresponding author Michael Stumpp goes #behindthepaper on the DARPin ensovibep, a potent, trispecific spike inhibitor designed to neutralize most SARS-CoV-2 variants https://t.co/OzGx8utFb2" (@NatureBiotech)

Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

The trispecific DARPin ensovibep inhibits diverse SARS-CoV-2 variants. (PubMed, Nat Biotechnol) - "When used as a single agent in viral passaging experiments in vitro, ensovibep reduced the emergence of escape mutations in a similar fashion to the same mAb cocktail. These results support further clinical evaluation of ensovibep as a broad variant alternative to existing targeted therapies for Coronavirus Disease 2019 (COVID-19)."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

EMPATHY: A Dose Finding, Efficacy and Safety Study of Ensovibep (MP0420) in Ambulatory Patients With Symptomatic COVID-19 (clinicaltrials.gov) - P2/3 | N=407 | Terminated | Sponsor: Novartis Pharmaceuticals | Due to the evolving landscape of treatments for COVID-19, the placebo-controlled Phase 3 design will not proceed. No patients were actively participating at the time of termination.

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

SARS-CoV-2 Omicron And Pan-variant Neutralization Activity Of Ensovibep: A DARPin Therapeutic Candidate For Treatment Of Covid-19 (ASM Microbe 2022) - "Ensovibep’s pan-variant in vitro activity against omicron and other variants of concern supports its continued clinical development. The clinical benefit of ensovibep is being evaluated in the Phase 2b/3 EMPATHY trial.Table >"

Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Therapeutic innovations in COVID-19: anti-spike biologics with pan-variant activity (ECCMID 2022) - "Organised by: Novartis To inform ECCMID delegates and the wider scientific and medical community of the mode of action and clinical data on ensovibep, a Designed Ankyrin Repeat Protein (DARPin) anti-spike biologic therapeutic, for the treatment of COVID-19."

Infectious Disease • Novel Coronavirus Disease

Interim results from the randomised, controlled EMPATHY phase II/III study evaluating ensovibep, a DARPin therapeutic, in patients with mild-to-moderate COVID-19 (ECCMID 2022) - No abstract available

Clinical • Late-breaking abstract • P2/3 data • Infectious Disease • Novel Coronavirus Disease