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A randomized, double-blind, Phase 1 study of IN-006, an inhaled antibody treatment for COVID-19

Moench et al., medRxiv, doi:10.1101/2022.08.17.22278748, ACTRN12621001235897

Aug 2022

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Regdanvimab

34th treatment shown to reduce risk in March 2022

^*, now known with p = 0.0000000045 from 10 studies, recognized in 27 countries. Efficacy is variant dependent.

Lower risk for mortality, hospitalization, progression, and recovery.

No treatment is 100% effective. Protocols combine complementary and synergistic treatments. ^* >10% efficacy in meta analysis with ≥3 clinical studies.

4,100+ studies for 60+ treatments. c19early.org

Phase 1 study of 23 healthy adults showing inhaled regdanvimab (IN-006) was well tolerated after single doses of 30mg and 90mg and 7 daily 90mg doses. High concentrations were achieved in nasal fluids and serum, over 1000 times the inhibitory concentration against SARS-CoV-2 for over 24 hours.

Efficacy is variant dependent. In Vitro research suggests a lack of efficacy for omicron BA.2, BA.4, BA.5 Haars, ХВВ.1.9.1, XBB.1.9.3, XBB.1.5.24, XBB.1.16, XBB.2.9, BQ.1.1.45, CL.1, and CH.1.1 Pochtovyi.

1. Haars et al., Prevalence of SARS-CoV-2 Omicron Sublineages and Spike Protein Mutations Conferring Resistance against Monoclonal Antibodies in a Swedish Cohort during 2022–2023, Microorganisms, doi:10.3390/microorganisms11102417.mdpi.com, doi.org.

2. Pochtovyi et al., In Vitro Efficacy of Antivirals and Monoclonal Antibodies against SARS-CoV-2 Omicron Lineages XBB.1.9.1, XBB.1.9.3, XBB.1.5, XBB.1.16, XBB.2.4, BQ.1.1.45, CH.1.1, and CL.1, Vaccines, doi:10.3390/vaccines11101533.mdpi.com, doi.org.

Important missing comments or errors? Let us know.

Moench et al., 21 Aug 2022, Double Blind Randomized Controlled Trial, placebo-controlled, preprint, 17 authors, trial ACTRN12621001235897. Contact: moench@inhalon.com, lai@inhalon.com.

This Paper Regdanvimab All

A randomized, double-blind, Phase 1 study of IN-006, an inhaled antibody treatment for COVID-19

Thomas R Moench, Lakshmi Botta, Brian Farrer, Jason D Lickliter, Hyunah Kang, Yoona Park, Cheolmin Kim, Marshall Hoke, Miles Brennan, Morgan D Mcsweeney, Zachary Richardson, John B Whelan, Jong Moon Cho, Soo Young Lee, Frances Faurot, Jeff Hutchins, Samuel K Lai

doi:10.1101/2022.08.17.22278748

Rationale: Although COVID-19 is predominantly a respiratory tract infection, current antibody treatments are administered by systemic dosing. We hypothesize that inhaled delivery of a mucotrapping monoclonal antibody would provide a more effective and convenient treatment for COVID-19. Objective: We investigated the safety, tolerability, and pharmacokinetics of IN-006, a reformulation of regdanvimab, an approved intravenous treatment for COVID-19, for nebulized delivery by a handheld nebulizer. Methods: A Phase 1 study was conducted in healthy volunteers. Study staff and participants were blinded to treatment assignment, except for pharmacy staff preparing the study drug. The primary outcomes were safety and tolerability. Exploratory outcomes were pharmacokinetic measurements of IN-006 in nasal fluid and serum. Results: Twenty-three participants were enrolled and randomized across two single dose and one multiple dose cohorts. There were no serious adverse events (SAEs). All enrolled participants completed the study without treatment interruption or discontinuation. All treatment-emergent adverse events were transient, non-dose dependent, and were graded mild to moderate in severity. Nebulization was well tolerated and completed in a mean of 6 minutes in the high dose group. Mean nasal fluid concentrations of IN-006 in the multiple dose cohort were 921 µg/g of nasal fluid at 30 minutes after dosing and 5.8 µg/g at 22 hours. Mean serum levels in the multiple dose cohort peaked at 0.55 µg/mL at 3 days after the final dose. Conclusions IN-006 was well-tolerated and achieved concentrations in the respiratory tract orders of magnitude above its inhibitory concentration. These data support further clinical development of

References

Bodier-Montagutelli, Designing inhaled protein therapeutics for topical lung delivery: what are the next steps?, Expert Opin Drug Deliv

Bodier-Montagutelli, Protein stability during nebulization: Mind the collection step!, Eur J Pharm Biopharm

Chen, SARS-CoV-2 shedding dynamics across the respiratory tract, sex, and disease severity for adult and pediatric COVID-19, eLife

Cruz-Teran, Challenges and opportunities for antiviral monoclonal antibodies as COVID-19 therapy, Adv Drug Deliv Rev

Dall'acqua, Kiener, Wu, Properties of human IgG1s engineered for enhanced binding to the neonatal Fc receptor (FcRn), J Biol Chem

Darquenne, Aerosol deposition in health and disease, Journal of aerosol medicine and pulmonary drug delivery

Emma, Short and Long Term Repeatability of Saccharin Transit Time in Current, Former, and Never Smokers, Front Physiol

Han, Safety and Efficacy of CR6261 in an Influenza A H1N1 Healthy Human Challenge Model, Clin Infect Dis

Hart, Preclinical efficacy and safety of mepolizumab (SB-240563), a humanized monoclonal antibody to IL-5, in cynomolgus monkeys, J Allergy Clin Immunol

Hou, SARS-CoV-2 Reverse Genetics Reveals a Variable Infection Gradient in the Respiratory Tract, Cell

Jia, ACE2 receptor expression and severe acute respiratory syndrome coronavirus infection depend on differentiation of human airway epithelia, J Virol

Lai, Mcsweeney, Pickles, Learning from past failures: Challenges with monoclonal antibody therapies for COVID-19, J Control Release

Lee, ACE2 localizes to the respiratory cilia and is not increased by ACE inhibitors or ARBs, Nature Communications

Lim, Modeling the early temporal dynamics of viral load in respiratory tract specimens of COVID-19 patients in Incheon, the Republic of Korea, International Journal of Infectious Diseases

Liu, Striking antibody evasion manifested by the Omicron variant of SARS-CoV-2, Nature

Loira-Pastoriza, Todoroff, Vanbever, Delivery strategies for sustained drug release in the lungs, Adv Drug Deliv Rev

Mayor, Inhaled antibodies: formulations require specific development to overcome instability due to nebulization, Drug Deliv Transl Res

Mcsweeney, Stable nebulization and muco-trapping properties of Regdanvimab/IN-006 supports its development as a potent, dose-saving inhaled therapy for COVID-19, bioRxiv

Nagy, Safety, Pharmacokinetics, and Immunogenicity of Obiltoxaximab After Intramuscular Administration to Healthy Humans, Clinical pharmacology in drug development

Pinto, Ultrastructural insight into SARS-CoV-2 entry and budding in human airway epithelium, Nature Communications

Ram-Mohan, SARS-CoV-2 RNAemia Predicts Clinical Deterioration and Extrapulmonary Complications from COVID-19, Clin Infect Dis

Respaud, Nebulization as a delivery method for mAbs in respiratory diseases, Expert Opin Drug Deliv

Rodrigues, Particularities and Clinical Applicability of Saccharin Transit Time Test, Int Arch Otorhinolaryngol

Sims, SARS-CoV replication and pathogenesis in an in vitro model of the human conducting airway epithelium, Virus Res

Suri, The use of human deoxyribonuclease (rhDNase) in the management of cystic fibrosis, BioDrugs

Syed, Regdanvimab: First Approval, Drugs

Van Der Straten, Optimization of Anti-SARS-CoV-2 Neutralizing Antibody Therapies: Roadmap to Improve Clinical Effectiveness and Implementation, Front Med Technol

Wang, Detection of SARS-CoV-2 in Different Types of Clinical Specimens, Jama

Zhang, Infection of ciliated cells by human parainfluenza virus type 3 in an in vitro model of human airway epithelium, J Virol

Zhang, Respiratory syncytial virus infection of human airway epithelial cells is polarized, specific to ciliated cells, and without obvious cytopathology, J Virol

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Exploratory outcomes were pharmacokinetic measurements ' 'of IN-006 in nasal fluid and ' 'serum.ResultsTwenty-three ' 'participants were enrolled and randomized across two single dose and one multiple dose ' 'cohorts. There were no serious adverse events (SAEs). All enrolled participants completed the ' 'study without treatment interruption or discontinuation. All treatment-emergent adverse ' 'events were transient, non-dose dependent, and were graded mild to moderate in severity. ' 'Nebulization was well tolerated and completed in a mean of 6 minutes in the high dose group. ' 'Mean nasal fluid concentrations of IN-006 in the multiple dose cohort were 921 µg/g of nasal ' 'fluid at 30 minutes after dosing and 5.8 µg/g at 22 hours. Mean serum levels in the multiple ' 'dose cohort peaked at 0.55 µg/mL at 3 days after the final ' 'dose.ConclusionsIN-006 was ' 'well-tolerated and achieved concentrations in the respiratory tract orders of magnitude above ' 'its inhibitory concentration. 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