Clinical Trials

Date: 2017-06-17

Type of information: Presentation of results at a congress

phase: 1

Announcement: presentation of results at the European League Against Rheumatism Annual Congress (EULAR)

Company: Macrogenics (USA - MD)

Product: MGD010

Action mechanism:

• bispecific antibody. MGD010 is a humanized DART compound that simultaneously targets CD32B and CD79B. In pre-clinical studies, MGD010 was shown to modulate the function of human B cells without B-cell depletion. In normal conditions, B cells utilize CD32B as one of the key negative regulators to ensure that tolerance to self is maintained and autoimmune disease does not occur. MGD010 exploits this mechanism and triggers this inhibitory "immune checkpoint" loop for the inhibition of B-cell function, an approach that may be useful for the treatment of patients with autoimmune disorders.
• In May 2014 , MacroGenics entered into an option agreement for the development and commercialization of MGD010 with Takeda. Macrogenics has regained  worldwide rights in September 2016. Takeda's decision comes earlier than the predefined expiration of its option exercise period and follows Takeda's recently announced therapeutic area re-prioritization.

Disease: autoimmune diseases

Therapeutic area: Autoimmune diseases

Country: USA

Trial details:

• The primary goal of this Phase 1 study is to assess the safety and tolerability of one MGD010 intravenous infusion in healthy adult volunteers. (NCT02376036)

Latest news:

• • On June 17, 2017, MacroGenics announced the presentation of updated data from its Phase 1 study of MGD010 at the European League Against Rheumatism (EULAR) Annual European Congress of Rheumatology in Madrid, Spain. In a poster titled "Immunomodulatory Effects of MGD010, a DART® Molecule Targeting Human B-cell CD32B and CD79B," the company highlighted the immunomodulatory impact of MGD010 on the response to hepatitis A vaccination (HAV), a model antigen challenge, in normal healthy subjects. These data demonstrate that by pharmacologically exploiting the activity of the checkpoint molecule CD32B in combination with the B-cell receptor (BCR) CD79B component, a single dose administration of MGD010 at either 3 or 10 mg/kg delivers an immunomodulatory effect that counters B-cell function. In this portion of the Phase 1 study, 23 evaluable healthy subjects received 3 or 10 mg/kg MGD010 or placebo, followed by HAV immunization. There were no CTCAE grade 3 or higher adverse events related to MGD010. Consistent with prior observations, ex vivo flow cytometric analysis confirmed dose-dependent MGD010 binding to peripheral B cells without B-cell depletion, accompanied by decreased surface BCR and CD40 expression as well as a decrease in total serum IgM levels. Compared to the placebo group, reduced HAV seroconversion rates were observed in subjects treated with MGD010, with significantly lower HA-specific IgG levels. MacroGenics reported initial data from a Phase 1 study of MGD010 at EULAR 2016 (see below).
• • On June 10, 2016, MacroGenics announced the oral presentation of clinical data from its Phase 1 study of MGD010 at the Annual European Congress of Rheumatology (EULAR 2016). Naimish Pandya, M.D., Senior Medical Director at MacroGenics, presented "Safety, Tolerability, and Functional Activity of MGD010, a DART® Molecule Targeting CD32B and CD79B, Following a Single Dose Administration in Healthy Volunteers." The objectives of the study were to assess the safety, tolerability, pharmacokinetic and pharmacodynamic activity of MGD010 in healthy volunteers. The Phase 1 study of MGD010 was a first-in-human, double-blind, placebo-controlled study in which a single dose of MGD010 was intravenously (IV) administered to 49 healthy subjects. Data from the study showed that MGD010 was well tolerated at all dose levels and no serious adverse effects were reported. None of the subjects participating in the study had premature discontinuations or infusion reactions, systemic hypersensitivity reactions or injection site reactions.
• In addition, MGD010 demonstrated linear pharmacokinetics and dose-dependent selective binding to B lymphocytes without persistent B-cell depletion. The data also showed: (1) a dose-dependent downregulation of B-cell receptor-induced signaling together with down-modulation of B-cell receptor expression among circulating memory and naïve B cells, (2) a decrease in expression of the costimulatory CD40 molecule and (3) a decrease in circulating immunoglobulin M levels, each consistent with the targeted action of MGD010. These data support the continued research and development of MGD010 in patients with autoimmune and inflammatory disorders.
• • On March 16, 2015, MacroGenics announced the initiation of a Phase 1 study with MGD010, its first Dual-Affinity Re-Targeting (DART®) molecule being developed for patients with autoimmune disorders. As a result of the study initiation, MacroGenics will receive a $3 million milestone payment from its partner, Takeda. The recently-initiated Phase 1 clinical trial is a first-in-human, double-blind, placebo-controlled, single ascending dose study to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and immunogenicity of MGD010 in healthy subjects.

   

Is general: Yes