The Antibody Society

the official website of the antibody society

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

You are here: Home / Archives for Ab news

Antibody Drug Conjugates – Clinical Progress

by

square logo ADCIn the second half of May several companies reported important progress on their therapeutic ADC products. The Dutch pharmaceutical company Synthon initiated the second phase of the ongoing phase I clinical trial with its investigational anti-HER2 ADC SYD985. During the first part patients with solid tumors of any origin were enrolled. Promising results were obtained in this dose-finding part of the trial in 33 cancer patients who were dosed with between 0.3 and 2.4 mg/kg of SYD985 every three weeks. Very high response rates and durable responses were observed  at doses from 1.2 mg/kg onwards in patients whose cancers were refractory to HER2-targeted agents, including Herceptin® and Kadcyla®. The second part will see 48 additional heavily pre-treated patients with HER2-positive breast cancer enrolled into the Phase I trial. This marked a significant next step in the development of SYD985, the frontrunner of the company’s duocarmycin-based ADC platform.

Additionally, Seattle Genetics announced initiation of a pivotal phase III clinical trial, CASCADE, evaluating vadastuximab talirine (SGN-CD33A) in combination with azacitidine (Vidaza) or decitabine (Dacogen) in older patients with newly diagnosed acute myeloid leukemia (AML). SGN-CD33A is an ADC targeting CD33 comprising an engineered cysteine antibody (EC-mAb) stably linked to a pyrrolobenzodiazepine (PBD) dimer. CD33 is expressed on leukemic blasts in nearly all AML patients and expression is generally consistent regardless of age, cytogenetic abnormalities or underlying mutations. Azacitidine and decitabine are hypomethylating agents (HMAs) commonly used in the treatment of older AML patients. The phase III CASCADE study is a randomized, double-blinded, placebo-controlled, global clinical trial. Patients will be randomized on a 1:1 ratio to be treated with an HMA plus SGN-CD33A or an HMA plus placebo. The secondary endpoints include the comparison of composite complete remission rate, event-free and leukemia-free survival, duration of response, safety, and 30- and 60-day mortality rates. This phase III trial will enroll approximately 500 patients globally.

Atezolizumab: 4th mAb granted a first approval in 2016

by

20150625-example-imageOn May 18, 2016, anti-PD-L1 atezolizumab (Tecentriq®) was approved by the Food and Drug Administration (FDA) as a treatment for patients with locally advanced or metastatic urothelial carcinoma. The marketing application for atezolizumab had received breakthrough therapy designation, priority review status and accelerated approval for this indication. A PD-L1 (SP142) assay complementary diagnostic to detect PD-L1 protein expression levels on the tumor-infiltrating immune cells of patients was also approved. An FDA action on a second application for use of atezolizumab as a treatment for patients with non-small cell lung cancer is expected by October 2016. Atezolizumab is the fourth antibody that inhibits an immune checkpoint to be granted a marketing approval. Two anti-PD1 antibodies, nivolumab (Opdivo®) and pembrolizumab (Keytruda®), were approved in 2014 in the US (2015 in the EU), and one anti-CTLA4 antibody, ipilimumab (Yervoy®), was approved in the US and EU in 2011. Atezolizumab is the fourth antibody product to be granted a first marketing approval in 2016.

Six additional antibody therapeutics (bezlotoxumab, sarilumab, brodalumab, Xilonix, begelomab, olaratumab) are now undergoing their first regulatory review in the European Union and the United States. If these antibodies are approved by the end of the year, the number of first approvals for antibody products in 2016 will set a new record (10 products), exceeding by 1 the previous record set in 2015. The Antibody Society maintains a comprehensive table of approved antibody therapeutics and those in regulatory review in the European Union and the Unites States. The antibody’s target, format and year of first approval are included. Please log in to access the table, located in the Members Only section.

Not a member? Please join!

Antibody Drug Conjugates – Acquisitions and Partnering

by

 
AbbVie dominated the news in the last weeks of April after announcing the acquisition of Stemcentrx including the company’s late-stage rovalpituzumab tesirine (Rova-T) for $5.8bn. Furthermore, AbbVie partnered up with CytomX to jointly develop and commercialize a probody-drug conjugate (PDC) against CD71.

Stemcentrx’ Rova-T, also known as SC16LD6.5, is addressing small cell lung cancer (SCLC) and other neuroendocrine cancers such as large cell neuroendocrine carcinoma. Rova-T has received orphan drug designation from the FDA for treatment of small cell lung cancer. Rova-T targets delta-like protein 3 (DLL3), which is expressed in >80% SCLC patient tumors and is not present on healthy tissue. Rova-T comprises a D6.5 pyrrolobenzodiazepine (PBD) payload conjugated to cysteine residues on the SC16 antibody, a maleimide-containing linker with an eight-carbon polyethylene glycol spacer, cathepsin B–cleavable valine-alanine dipeptide, and self-immolating group, with an average drug-to-antibody ratio (DAR) of 2. Rova-T represents a multi-billion dollar peak revenue opportunity with expected commercialization in 2018. The acquisition expands AbbVie’s oncology pipeline with four additional early-stage clinical compounds in solid tumor indications and Stemcentrx’ portfolio of preclinical assets.

 

Together with CytomX, AbbVie will co-develop a PDC against CD71. PDCs contain a masking peptide designed to decreasing target binding to healthy tissue and remain inactive until the molecules are activated proteolytically in the tumor microenvironment, thereby minimizing toxicities. The target, transferrin receptor 1 (TfR1), also known as CD71, is ubiquitously expressed on dividing, normal or healthy cells plus a number of hematologic and solid malignant cancer cells. CD71 mediates transferrin-iron complex uptake, an essential process for cell division and therefore also for tumors. CD71 is homogeneously and highly expressed (3+ expression assessed by IHC) in almost all tumor types, including metastatic tumors. The current PDC approach should avoid targeting the many healthy cell types that also express CD71.

 

Additionally, Regeneron Pharmaceuticals and MedImmune (wholly owned subsidiary of  AstraZeneca) entered into a licensing agreement under which Regeneron will use MedImmune’s PBD-based payload and linker technology to develop ADCs against a number of cancer targets. MedImmune will have the option to develop and commercialize certain products created with this technology in territories outside of the United States.

Reslizumab: Third mAb approved in 2016

by

On March 23, reslizumab (Cinqair®) became the third new monoclonal antibody product to be approved in 2016. Reslizumab targets IL-5, and it was approved by the Food and Drug Administration for use with other asthma medicines for the maintenance treatment of severe asthma in patients aged 18 years and older who have a history of severe asthma attacks (exacerbations) despite receiving their current asthma medicines. A marketing application for reslizumab is undergoing review by the European Medicines Agency.

WHO’s Open Session on INN to be held on April 12, 2016

by

The World Health Organization (WHO) recently introduced new definitions for the assignment of antibody international nonproprietary names (INN). Linear protein sequence is now used to define humanness, which is a substantial change in the method by which therapeutic antibodies were previously classified as chimeric, humanized or human. The new definitions are scientifically flawed, provide results that are inconsistent with names of many existing antibody therapeutics, and do not consider advances in antibody technology and antibody development experience.

The Antibody Society will represent the Antibody Community at large at the WHO’s Open Session at the 62nd consultation on INN for pharmaceutical substances in Geneva on April 12, 2016, and we will request modifications that address the problems with the new system.
To be able to influence the WHO, we need your support. Please support our effort by agreeing to the statement here, and provide your name and contact information.

The Antibody Society’s presentation at the WHO’s Open Session on April 12, 2016 is available to Society members. Please log in to access the presentation, located on the Presentations page in the Members Only section.

Not a member? Please join!