Archives for January 2017

Free virtual issue featuring articles on neonatal Fc receptor is online now

January 31, 2017 by Janice Reichert

In a special issue of mAbs, Guest Editor Zita Schneider, D.V.M., Ph.D., Texas A&M Health Science Center, has compiled 12 articles describing recent results obtained about the neonatal Fc receptor, FcRn. All articles can be freely downloaded for a limited time. As a regulator of immunoglobulin G (IgG) and albumin homeostasis and a modulator of immune functions, this receptor has been attracting the interest of the scientific community and has become an unavoidable factor for consideration in the development of IgG- and albumin-based diagnostic and therapeutic reagents.

Burvenich et al. identified important amino acids playing a role in FcRn-IgG interaction, whereas Hironiwa et al. showed efficient antigen drop-off and IgG recycling utilizing calcium-dependent antigen-antibody binding. Ying and colleagues provided a tool to increase the transcytosis and half-life of engineered antibody domains through an FcRn-binding motif, whereas Meyer et al. utilized the albumin-binding characteristics of FcRn to generate IgA molecules with elongated half-life. Adams et al. used an anti-albumin Fv domain to extend the half-life of an Fab fragment, and Davé et al. used this domain to generate an Fab-dsFv bispecific antibody format.

FcRn can also serve as a screening tool for antibody selection as demonstrated by Souders et al. who developed a novel FcRn-binding biolayer interferometry assay, while Fan and colleagues used online peptide immune-affinity chromatography coupled with high resolution mass spectrometry to determine human FcRn expression levels in transgenic (Tg) mice and Avery et al. characterized these human FcRn Tg mice with respect to mAb pharmacokinetics (PK) prediction. Unverdorben et al. provided details of the PK of various Fc fusions compared to IgG molecules, Kelly et al. proved that FcRn-independent antigen-independent nonspecific interactions can also play a role in antibody PK, and Datta-Mannan et al. investigated several properties of mAbs in order to optimize PK parameters.

These articles provide valuable details to explore the possibilities offered by utilizing the functions of FcRn.

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Increased clinical pipeline of Antibody Drug Conjugates in 2016

January 25, 2017 by Joost Melis

The antibody-drug conjugate (ADC) clinical pipeline has continued to grow in 2016. Last month two ADCs entered the clinic: Genmab’s MMAE-conjugated HuMax-AXL-ADC is now in Phase 1/2 development for five different types of solid tumors (ovary, cervix, endometrium, lung and thyroid). Additionally, a PBD-conjugated ADC for multiple myeloma (SGN-CD352A), was added to Seattle Genetics’ clinical pipeline.

In total, 32 clinical trials involving ADCs were initiated in 2016 and a significant progression of the pipeline into Phase 2 and 3 clinical trial was observed that year. During last year, 14 novel ADCs entered Phase 1, now totaling 37 Phase 1 ADCs. Three ADCs initiated Phase 1/2 development in 2016, increasing the total number of ADCs in this stage to 8. Four ADCs (AGS-16C3F, Anetumab Ravtansine, SAR566658, Rova-T) progressed towards Phase 2 (11 ADCs are now in Phase 2) and two drugs (IMGN853, SGN-CD33A) entered Phase 3 trials, doubling the number of ADCs in this clinical phase.

This year, a market approval could become a reality for inotuzumab ozogamicin. Currently, a marketing authorization application for acute lymphocytic leukemia (ALL) is being reviewed by EMA. Another possible approval is the re-approval for Mylotarg using a different dosing regimen.

New guidance available from FDA on nonproprietary naming of biological products

January 13, 2017 by Janice Reichert

The US Food and Drug Administration (FDA) has released new guidance for industry on nonproprietary naming of biological products licensed under the Public Health Service (PHS) Act. The guidance describes FDA’s current thinking on the need for nonproprietary names that include a core name and an FDA-designated suffix. Such ‘proper names’, which are the nonproprietary names designated by FDA in the license for a biological product licensed under the PHS Act, will include a distinguishing suffix that is composed of 4 lowercase letters devoid of meaning attached to a core name with a hyphen. For example, replicamab-cznm and replicamab-hjxf represent proper names for two products sharing one core name (replicamab). The FDA intends to use the adopted name designated by the US Adopted Name (USAN) Council as the core name for the relevant biological when available. FDA’s current thinking is that proper names including the suffix are warranted for originator biological products, related biological products and biosimilar products to facilitate pharmacovigilance and accurate identification by health care practitioners and patients, and to help minimize inadvertent substitution of products not determined to be interchangeable. Prospective naming, retrospective naming and naming of biosimilar products are discussed in the guidance. For prospective naming and naming of biosimilar products, the applicants should propose a suffix; in the case of retrospective naming of licensed products, the biological license application holders may propose a suffix.

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mAb first approvals in 2017 may set a new record

January 10, 2017 by Janice Reichert

A new record for the number of monoclonal antibody (mAb) therapeutics granted their first marketing approval during a single year may be set in 2017. The previous record was set in 2015, when 8 antibody therapeutics were granted first approvals. Remarkably, 11 investigational mAb therapeutics are currently being considered for first marketing approvals that may be granted in 2017. Of these, 4 mAbs are under review as treatments for common immune-mediated disorders such as dermatitis, psoriasis and rheumatoid arthritis (anti-IL-6 sirukumab, anti-IL-6R sarilumab, anti-IL-4Ra dupilumab and anti- IL-23p19 guselkumab), 4 mAbs are under review as treatments for various types of cancer (anti-IL-1 alpha Xilonix, anti-CD22 inotuzumab ozogamicin, anti-PD-L1 avelumab and anti-PD-L1 durvalumab) and 3 mAbs are under review as treatments for other disorders (anti-CD20 ocrelizumab for multiple sclerosis, anti-sclerostin romosozumab for osteoporosis and anti-FGF23 burosumab for X-linked hypophosphatemia). Marketing applications for additional mAb therapeutics may be submitted to regulatory agencies during the first half of 2017, which could allow additional first approvals to occur during 2017.

Additional information on antibody therapeutics in Phase 3 clinical studies, regulatory review and those recently approved can be found in the ‘Antibodies to watch in 2017’ article, which can be freely downloaded.

The Antibody Society will post reports on the progress of mAb therapeutics during 2017, with an emphasis on first marketing application submissions and approvals in the European Union, United States and Japan. The Society maintains a comprehensive table of approved antibody therapeutics and those in regulatory review in the EU or US. Please log in to access the table, located in the Members Only section.

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