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Alternative Routes of Administration for Therapeutic Antibodies-State of the Art

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Intra-articular delivery of full-length antibodies through the use of an in situ forming depot

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Summary: Monoclonal antibodies have high therapeutic potential for cancer or autoimmune diseases, but intravenous administration can lead to off-target effects. Utilizing a local controlled-delivery approach with in situ forming depot technology can help address this issue.

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Efficacy, durability, and safety of intravitreal faricimab up to every 16 weeks for neovascular age-related macular degeneration (TENAYA and LUCERNE): two randomised, double-masked, phase 3, non-inferiority trials

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Summary: The primary results of two Phase 3 trials show that faricimab can effectively improve visual acuity for patients with nAMD at intervals of up to 16 weeks, with comparable safety profile to aflibercept. This suggests that faricimab has the potential to reduce treatment burden by extending the time between injections while maintaining efficacy.

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Antibodies to watch in 2022

Helene Kaplon et al.

Summary: This article provides a summary of key events in the development of commercial antibody therapeutics in 2021 and a glimpse into potential events in 2022. The regulatory review process for antibody therapeutics targeting the SARS-CoV-2 coronavirus has been expedited, leading to emergency use authorizations and full approvals in multiple countries. Additionally, the late-stage commercial clinical pipeline for antibody therapeutics, excluding those for COVID-19, has seen significant growth over the past year.
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2021 FDA approvals

Asher Mullard

Summary: The FDA approved 50 novel drugs in 2021, including the first KRAS inhibitor for cancer and the first anti-amyloid antibody for Alzheimer's disease.

NATURE REVIEWS DRUG DISCOVERY (2022)

Review Pharmacology & Pharmacy

Therapeutic antibodies - natural and pathological barriers and strategies to overcome them

Yara Al Ojaimi et al.

Summary: Antibody-based therapeutics have become an important class of drugs, with over 120 recombinant antibodies approved or under review. The field of antibody therapy is expected to grow rapidly in 2021-2022, fueled by the global response to the SARS-CoV2 pandemic and the disclosure of numerous anti-SARS-CoV2 antibodies. In addition to intravenous delivery, alternative routes of administration have been developed to enhance therapeutic efficacy and patient comfort. Understanding the barriers antibodies face upon entering the body is essential for optimizing their delivery and improving treatment outcomes.

PHARMACOLOGY & THERAPEUTICS (2022)

Article Pharmacology & Pharmacy

KSI-301: an investigational anti-VEGF biopolymer conjugate for retinal diseases

Hudson D. Stern et al.

Summary: KSI-301 is an intravitreal anti-VEGF agent with potential as a durable therapy. Despite varied results in studies for nAMD, ongoing clinical trials will provide additional evidence on its efficacy, duration, and safety profiles.

EXPERT OPINION ON INVESTIGATIONAL DRUGS (2022)

Review Oncology

Intratumoral Immunotherapy and Tumor Ablation: A Local Approach with Broad Potential

Zachary J. Senders et al.

Summary: The goal of immuno-oncology is to enhance the antitumor immune response. The tumor microenvironment presents challenges to current therapies. Combining intratumoral immunotherapy with tumor ablation addresses these challenges. This review evaluates the data and suggests that combination therapy can enhance the immune response and should be further studied in clinical practice.

CANCERS (2022)

Article Pharmacology & Pharmacy

Aggregates Associated with Instability of Antibodies during Aerosolization Induce Adverse Immunological Effects

Thomas Secher et al.

Summary: The study investigated the impact of aggregates produced during the aerosolization of therapeutic antibodies on the immune system. It was found that aggregated antibodies led to immune cell activation and subsequent cell death.

PHARMACEUTICS (2022)

Review Oncology

Intratumoral Immunotherapy: From Trial Design to Clinical Practice

Stephane Champiat et al.

Summary: Intratumoral immunotherapies have shown promising effects by stimulating the immune system through the injection of immune stimulatory products in certain solid tumor types. This approach can transform cold tumors into hot tumors, enhance the response rates to cancer immunotherapies, and reduce side effects, leading to improved long-term survival rates for patients.

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Article Critical Care Medicine

Nebulised ALX-0171 for respiratory syncytial virus lower respiratory tract infection in hospitalised children: a double-blind, randomised, placebo-controlled, phase 2b trial

Steve Cunningham et al.

Summary: This study evaluated the safety and antiviral activity of nebulised ALX-0171 in children hospitalized with RSV lower respiratory tract infection. Results showed faster viral load reduction with ALX-0171 treatment compared to placebo, but no significant improvement in clinical outcomes. Safety profile was similar between ALX-0171 and placebo groups. Future RSV antiviral studies should consider earlier intervention and more precise measurement of objective outcomes.

LANCET RESPIRATORY MEDICINE (2021)

News Item Biotechnology & Applied Microbiology

2020 FDA drug approvals

Asher Mullard

Summary: In 2020, the FDA approved 53 novel drugs, the second highest count in over 20 years.

NATURE REVIEWS DRUG DISCOVERY (2021)

Article Medicine, General & Internal

REGN-COV2, a Neutralizing Antibody Cocktail, in Outpatients with Covid-19

D. M. Weinreich et al.

Summary: Recent data indicate that complications and death from Covid-19 may be related to high viral loads. In this trial involving nonhospitalized patients, a cocktail of two neutralizing monoclonal antibodies (REGN-COV2) reduced viral load, with a greater effect in patients with no immune response or high viral load at baseline. Safety outcomes were similar between REGN-COV2 dose groups and the placebo group.

NEW ENGLAND JOURNAL OF MEDICINE (2021)

Review Pharmacology & Pharmacy

Challenges and opportunities for antiviral monoclonal antibodies as COVID-19 therapy

Carlos Cruz-Teran et al.

Summary: The article discusses the global efforts to combat the COVID-19 pandemic with potent neutralizing mAbs and highlights the challenges faced by current antiviral mAbs. It also presents evidence supporting inhaled delivery of antiviral mAbs as an early intervention against COVID-19.

ADVANCED DRUG DELIVERY REVIEWS (2021)

Review Pharmacology & Pharmacy

Penetration Enhancers for Topical Drug Delivery to the Ocular Posterior Segment-A Systematic Review

Abhinav Thareja et al.

Summary: There is a clinical need for efficient eye drop formulations to treat posterior ocular segment diseases non-invasively. Cell penetrating peptides (CPPs), TAT, and penetratin are inferred as the most efficient penetration enhancers for drug delivery to the fundus oculi via topical eye drop instillation, but further high-quality experimental studies are needed for quantitative efficacy confirmation.

PHARMACEUTICS (2021)

Review Chemistry, Medicinal

A review of formulations of commercially available antibodies

Robert G. Strickley et al.

Summary: This review examines 126 commercially available antibodies approved globally between 1986 and February 2021, including various formulations, routes of administration, and formulation components. The number of approved antibodies per year has increased significantly after 2014. Most antibody products are packaged in single-dose units, with different routes of administration and formulation components.

JOURNAL OF PHARMACEUTICAL SCIENCES (2021)

News Item Biotechnology & Applied Microbiology

FDA approves 100th monoclonal antibody product

Asher Mullard

Summary: After 35 years since the FDA approved the first monoclonal antibody, these biologics now make up nearly one fifth of the agency's new drug approvals each year.

NATURE REVIEWS DRUG DISCOVERY (2021)

Article Oncology

Efficacy, Safety, and Immunogenicity of HLX04 Versus Reference Bevacizumab in Combination with XELOX or mFOLFOX6 as First-Line Treatment for Metastatic Colorectal Cancer: Results of a Randomized, Double-Blind Phase III Study

Shukui Qin et al.

Summary: HLX04, a potential biosimilar to bevacizumab, demonstrated equivalent efficacy, safety, and immunogenicity profiles compared to reference bevacizumab in treating patients with recurrent/metastatic CRC. This supports the development of HLX04 as an alternative treatment option for patients.

BIODRUGS (2021)

Correction Pharmacology & Pharmacy

Aducanumab: First Approval (vol 81, pg 1437, 2021)

Sohita Dhillon

Review Biochemistry & Molecular Biology

Principles and Current Clinical Landscape of Multispecific Antibodies against Cancer

Mariam Elshiaty et al.

Summary: The field of multispecific therapeutic antibodies is growing rapidly, with over 140 different molecules currently in clinical testing and excellent results in recent clinical trials. Strategies for enhancing anticancer efficacy are focused on disrupting multiple surface antigens and redirecting cytotoxic lymphocytes, with a trend towards more target antigens and increased valency in newer constructs. Exciting prospects include targeting intracellular neoantigens using T-cell receptor fusion proteins or TCR-mimic antibody fragments, offering hope for cure of advanced cancers in the near future.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2021)

Article Immunology

Rabies virus neutralizing activity, pharmacokinetics, and safety of the monoclonal antibody mixture SYN023 in combination with rabies vaccination: Results of a phase 2, randomized, blinded, controlled trial

J. Bruce McClain et al.

Summary: The study compared SYN023 and HyperRab in terms of rabies virus neutralizing activity and safety. Results showed that SYN023 recipients had higher RVNA levels compared to HyperRab recipients and maintained adequate levels throughout the relevant period. Both treatment regimens exhibited similar safety profiles with no serious adverse events observed.

VACCINE (2021)

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Central Nervous System Delivery of Antibodies and Their Single-Domain Antibodies and Variable Fragment Derivatives with Focus on Intranasal Nose to Brain Administration

Arghavan Soleimanizadeh et al.

Summary: Antibodies play a crucial role in drug delivery, but their size and penetrative abilities limit their applications in tissues. Smaller antibody formats offer advantages such as reduced production costs and potential for targeted drug delivery.

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Review Biochemistry & Molecular Biology

Development and application of therapeutic antibodies against COVID-19

Lin Ning et al.

Summary: The global health crisis caused by the COVID-19 pandemic continues, with many therapeutic antibody treatments in development and authorized for emergency use by the FDA. Ongoing clinical trials worldwide have shown therapeutic antibody therapies to be a crucial part of COVID-19 treatment.

INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES (2021)

Review Ophthalmology

KSI-301: antibody biopolymer conjugate in retinal disorders

Priya R. Chandrasekaran et al.

Summary: KSI-301, a novel intravitreal anti-VEGF antibody biopolymer conjugate, has shown promising results in retinal vascular diseases with extended duration, durability, safety, and efficacy, potentially addressing treatment burden and improving outcomes.

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Faricimab: expanding horizon beyond VEGF

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Off-label use of bevacizumab for wet age-related macular degeneration in Europe

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Predicting bioavailability of monoclonal antibodies after subcutaneous administration: Open innovation challenge

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Drug Delivery to the Posterior Segment of the Eye: Biopharmaceutic and Pharmacokinetic Considerations

Ruben Varela-Fernandez et al.

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Monoclonal Antibodies in Cancer Therapy

David Zahavi et al.

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Subcutaneous tocilizumab: recent advances for the treatment of rheumatoid arthritis

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Inhaled Therapy in Respiratory Disease: The Complex Interplay of Pulmonary Kinetic Processes

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Palivizumab Prophylaxis for Respiratory Syncytial Virus: Examining the Evidence Around Value

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Pharmacokinetic aspects of retinal drug delivery

Eva M. del Amo et al.

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Mi Lan Kang et al.

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Subcutaneous Administration of Monoclonal Antibodies in Oncology

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