Methotrexate (MTX) is the first-line anti-rheumatic drug prescribed to treat newly diagnosed rheumatoid arthritis. However, in only 40% of the patients treated with just methotrexate disease remission is achieved.
Why does methotrexate not work sufficiently in the majority of the patients?
Scientists now understand the reason why. MTX is a prodrug and its clinical efficacy depends on intracellular conversion of MTX into long-chain polyglutamated MTX (MTX-PGn). However, ABCG2 transporter mediated efflux exports MTX from target cells before conversion to MTX-PGn occurs (see animation), slowing down and limiting response to treatment in many patients.
NovoBioJect is a proprietary composition of MTX with an ABCG2 inhibitor, locking the drug inside target cells, allowing increased formation of pharmacologically active MTX-PGn.
NovoBioJect, human biomarker based evidence of efficacy
NovoBioJect delivered a rapid increase in MTX-PGn in the pro-inflammotory cells (PBMCs) in RA patients compared to MTX alone, providing clinical biomarker-based Proof of Principle evidence that NovoBioJect may provide a faster treatment response in a much larger number of patients, compared to currently used methotrexate drug products.
NovoBioJect, combining methotrexate with an ABCG2 inhibitor
NovoBioJect will be marketed as a once a week subcutaneous administration via autoinjector. The ABCG2 inhibitor used in NovoBioJect is novobiocin, a known drug that has been marketed for many years, but not anymore. Novobiocin acts as an ABCG2 inhibitor at a fraction of the dose it was originally registered for. The combination of methotrexate and low dose novobiocin is novel and patents that cover the product, as well as its use, have been granted in US and Europe.