The Antibody Society

the official website of the antibody society

An international non-profit supporting antibody-related research and development.

FDA approves Evkeeza (evinacumab-dgnb) for homozygous familial hypercholesterolemia

by

On February 11, 2021, the US Food and Drug Administration approved Evkeeza (evinacumab-dgnb) injection as an add-on treatment for patients aged 12 years and older with homozygous familial hypercholesterolemia (HoFH), a genetic condition that causes severely high cholesterol. Evkeeza received orphan drug and breakthrough therapy designations for this indication, and the biological license application received a priority review.

Evinacumab is a human IgG4k antibody targeting angiopoietin-like 3 (ANGPTL3), which regulates the metabolism of plasma lipids, including low-density lipoprotein (LDL) cholesterol, high-density lipoprotein cholesterol, and triglycerides. The antibody was derived from Regeneron’s Velocimmune® technology platform, and includes a stabilizing mutation in the hinge region to minimize half-antibody formation.

Data from the Phase 3 ELIPSE trial (NCT03399786) was used as the basis of regulatory submissions. In this study 65 patients were randomized to receive either IV administration of evinacumab 15 mg/kg every four weeks (n=43) or placebo (n=22), plus other lipid-lowering therapies. The primary endpoint was the percent change from baseline in the LDL cholesterol level at Week 24. At baseline, LDL cholesterol was 260 mg/dL in the evinacumab group and 247 mg/dL in the placebo group. The primary endpoint of the study was met. Relative to baseline, the LDL cholesterol level at Week 24 was reduced by 47.1% in the patients administered evinacumab, but increased 1.9% in the placebo group.

Keep up to date on US and EU approvals all year by visiting our website!

The Antibody Society maintains a comprehensive table of approved monoclonal antibody therapeutics and those in regulatory review in the EU or US. The table, which is located in the Web Resources section of the Society’s website, can be downloaded in Excel format.

Evinacumab is the first investigational (i.e., not previously approved for any indication) antibody therapeutic to be granted an approval in the EU or US in 2021. There are currently 17 investigational antibody therapeutics in regulatory review in the EU or US.

FDA issues Emergency Use Authorization for bamlanivimab/etesevimab combination

by

On February 9, 2021, the U.S. Food and Drug Administration issued an emergency use authorization (EUA) for bamlanivimab and etesevimab administered together for the treatment of mild to moderate COVID-19 in adults and pediatric who test positive for SARS-CoV-2 and who are at high risk for progressing to severe COVID-19. Developed by Eli Lilly and Company, bamlanivimab and etesevimab are monoclonal antibodies (mAbs) that target overlapping regions of the SARS-CoV-2 spike protein.

The EUA was based on a randomized, double-blind, placebo-controlled clinical trial in 1,035 non-hospitalized adults with mild to moderate COVID-19 symptoms who were at high risk for progressing to severe COVID-19. Of these patients, 518 received a single infusion of bamlanivimab (2.8 g) and etesevimab (2.8 g) together, and 517 received placebo. The primary endpoint was COVID-19 related hospitalizations or death by any cause during 29 days of follow-up.  Hospitalization or death occurred in 11 (2%) patients treated the mAb combination vs. 36 (7%) patients who received placebo. All 10 deaths (2%) occurred in the placebo group.

The authorized dosage of 700 milligrams bamlanivimab and 1400 milligrams etesevimab administered together is based on analyses of available preclinical, clinical, and virologic data, as well as pharmacokinetic and pharmacodynamic modeling, which, in totality, support that the authorized dosage is expected to have a similar clinical and virologic effect to the dose evaluated in the clinical trial. Use of the mAb combination is not authorized for patients who are hospitalized due to COVID-19 or require oxygen therapy due to COVID-19.

In November 2020, FDA issued an EUA for a single infusion of 700 mg bamlanivimab for the treatment of mild-to-moderate COVID-19 in adult and certain pediatric patients. Since the monotherapy and the combination treatment are expected to benefit patients at high risk of disease progression, both 700 milligrams bamlanivimab alone and the combination of 700 milligrams bamlanivimab and 1,400 milligrams etesevimab administered together will be available under an EUA.

Call for Papers on Biopharmaceutical Informatics

by

As evident from papers published in mAbs in recent years, computation is being increasingly used in the discovery and development of antibody-based biologic drugs. To celebrate the rise of biopharmaceutical informatics directed towards antibody R & D, we invite The Antibody Society members, mAbs readers and the broader scientific community to contribute review articles focused on highlighting how computation has enabled their investigations or led them to new ones. The reviews should narrate the state of the art and speculate on new vistas for computational applications in the field.

We are particularly interested in reviews in the following topics:

  • Analyses of immune repertoires and their role in target validation and drug discovery.
  • Analyses of antibody structure-function relationships with emphasis on therapeutic antibody-based biologics.
  • Structure-based design of antibody fragments (e.g., nanobodies) and antibody-based multi-specific molecular formats.
  • Design of antibody libraries for different display strategies and/or with improved developability.
  • Structure-based affinity maturation and optimization of biologic lead candidates.
  • Molecular simulations of antibodies to understand their solution behaviors, such as aggregation, viscosity and physicochemical degradation.
  • Consideration of developability in biologic drug discovery and design.
  • Developability assessments at early-stage development.
  • Specific and non-specific interactions formed by antibodies in vitro and in vivo.
  • Computation in antibody formulations – design of novel excipients.
  • Applications of artificial Intelligence and machine learning towards antibody discovery, development and manufacturing.
  • Progress and challenges in modeling antibodies and multi-specific formats.
  • Predicting chemical degradation in antibody-based biologic drugs.
  • Optimizing antigens for greater immunization success.

Although these topics are especially of interest, we welcome well-written reviews in related areas as well.

Publication charges will be waived for six of the best review articles selected from pre-submission inquiries, which should consist of the title, abstract and general outline of the intended review article.

The deadline for the pre-submission enquiries is February 15, 2021, and the deadline for submission of the completed review articles is June 30, 2021.

Please send pre-submission inquiries to Assistant Editor Dr. Sandeep Kumar (skumarmabs@gmail.com) and Editor-in-Chief Dr. Janice Reichert (reichert.biotechconsulting@gmail.com), and contact us if you have any questions.

Antibodies to Watch in 2021 is now online!

by

Click here to download this newly published mAbs article!

In this 12th annual installment of the Antibodies to Watch article series, we discuss key events in antibody therapeutics development that occurred in 2020 and forecast events that might occur in 2021. The coronavirus disease 2019 (COVID-19) pandemic posed an array of challenges and opportunities to the healthcare system in 2020, and it will continue to do so in 2021. Remarkably, by late November 2020, two anti-SARS-CoV antibody products, bamlanivimab and the casirivimab and imdevimab cocktail, were authorized for emergency use by the US Food and Drug Administration (FDA) and the repurposed antibodies levilimab and itolizumab had been registered for emergency use as treatments for COVID-19 in Russia and India, respectively.

Despite the pandemic, 10 antibody therapeutics had been granted first approval in the US or EU in 2020, as of November, and 2 more (tanezumab and margetuximab) may be granted approvals in December 2020.* In addition, prolgolimab and olokizumab had been granted first approvals in Russia and cetuximab saratolacan sodium was first approved in Japan.

The number of approvals in 2021 may set a record, as marketing applications for 16 investigational antibody therapeutics are already undergoing regulatory review by either the FDA or the European Medicines Agency. Of these 16 mAbs, 11 are possible treatments for non-cancer indications and 5 are potential treatments for cancer.

Based on the information publicly available as of November 2020, 44 antibody therapeutics are in late-stage clinical studies for non-cancer indications, including 6 for COVID-19, and marketing applications for at least 6 (leronlimab, tezepelumab, faricimab, ligelizumab, garetosmab, and fasinumab) are planned in 2021. In addition, 44 antibody therapeutics are in late-stage clinical studies for cancer indications. Of these 44, marketing application submissions for 13 may be submitted by the end of 2021.

*Note added in proof on key events announced during December 1-21, 2020: margetuximab-cmkb and ansuvimab-zykl were approved by FDA on December 16 and 21, 2020, respectively; biologics license applications were submitted for ublituximab and amivantamab.

Keep up to date on US and EU approvals all year by visiting our website!

The Antibody Society maintains a comprehensive table of approved monoclonal antibody therapeutics and those in regulatory review in the EU or US. The table, which is located in the Web Resources section of the Society’s website, can be downloaded in Excel format.

Successful AIRR Community Meeting V

by

The fifth AIRR Community meeting (#AIRRC5) was held virtually Dec 8–10, 2020. The theme of this meeting was “Zooming in to the AIRR Community” connecting the global AIRR research community despite the pandemic for a series of Working Group & Sub-committee presentations, scientific sessions, interactive poster sessions, software tool demonstrations and networking events.

AIRR Community meetings are the premier event for research on adaptive immune-receptor repertoires. They are also the primary location where the AIRR-Community’s Working Groups and Sub-committees come together in one location to discuss how to push standardization in AIRR-sequencing (AIRR-seq) data and analysis forward.  All video recordings can be found here https://www.youtube.com/airrcommunity. All presentations can be found in the AIRR Community Resources section of the website. 

Just as the biology of AIRR is high-dimensional, this meeting’s success was as well!  We gathered some of the numbers that best describe the success of the #AIRRC5 meeting.

  • 1 Keynote speaker: Ignacio Sanz (Emory University School of Medicine, USA)
  • 3 Basic Science Presentations, 3 Biomedical Science Presentations
  • Attendees from 18 countries and 6 continents
  • 161 Registrants 
  • 5 Sponsors 
  • 6 Invited Speakers 
  • 2 Judging Panels 
  • 4 Short Talk Presenters 
  • 28 Poster Presenters 
  • 4 Software Demonstrators 
  • 9 Moderators 
  • 19 Community Presenters 
  • This was the second time a twitter hashtag was used for an AIRR Community Meeting (#AIRRV)
  • We achieved the milestone of more than 100 subscribers for the AIRRC YouTube channel thus enabling a custom YouTube URL: https://www.youtube.com/airrcommunity 
  • In addition to the main meeting, two free pre-meetings were held with over 175 participants
    • Pre-meeting 1: “AIRR-seq in the Pandemic” co-hosted by the AIRR Community and Tsinghua University in China which took place on December 5th/6th
    • Pre-meeting 2 “AIRR-seq Biological Standards and Workflows“ which was hosted by the Biological Resources Working Group on December 7th.