Biotie reports positive top-line data from clinical study with its third generation oral PDE4 inhibitor - ELB353 is well tolerated and shows clear pharmacological activity Biotie today reported that it has successfully completed a Phase I trial with its orally administered phosphodiesterase 4 (PDE4) inhibitor ELB353, intended for the treatment of chronic obstructive pulmonary disease (COPD).
The study evaluated the safety, tolerability, pharmacokinetic characteristics and pharmacodynamic effects of repeated oral doses of ELB353 in 48 healthy male volunteers. ELB353 was generally well tolerated, and no serious or severe adverse events were reported in any of the study subjects. The pharmacokinetic characteristics of ELB353 demonstrated its suitability for a once daily dosing regimen. Robust and statistically highly significant biomarker responses confirmed the pharmacological activity of well tolerated doses of ELB353 in man.
“We are very pleased with the properties of ELB353 seen in this study”, said Timo Veromaa, President and CEO of Biotie Therapies Corp. “These data, combined with the recommendation for approval of the first PDE4 inhibitor in the EU last week, confirm our commitment to move forward with a Phase II program in COPD patients and may also provide an interesting entry point for a partner into the development program.”
About Study BTT70-CD018
Study BTT70-CD018, conducted within the EU, was a randomized, placebo-controlled, double-blind multiple ascending dose study conducted in 6 sequential cohorts of 8 healthy male volunteers. Within each cohort, 6 patients were randomized to receive active drug and 2 patients to receive placebo under double-blind conditions. Study drugs were administered orally for 10 days, and the highest studied dose of ELB353 was 100 mg/day.
Safety and tolerability were evaluated with clinical assessments, adverse event inquiries, comprehensive laboratory analyses and Holter ECGs. Pharmacological activity was determined with a biomarker assay. This assay, which is performed with whole blood samples collected from the study subjects, measured the ability of ELB353 to inhibit lipopolysaccharide (LPS) -induced tumor necrosis factor alpha (TNFa) release from blood cells. Inhibition of LPS-induced TNFa release ex vivo is considered a clinically relevant and reliable biomarker of PDE4 inhibition.
As expected in an ascending dose design, the highest studied dose levels were associated with mild to moderate adverse events in some study subjects, but a maximum tolerated dose (MTD) was not reached. In the biomarker assay, TNFa release was decreased by up to 45% from baseline with well tolerated doses of ELB353, whereas no decrease from baseline occurred with placebo.
About ELB353
ELB353 stems from Biotie’s proprietary PDE technology platform. It is a third generation orally administered PDE4 inhibitor with therapeutic potential in chronic inflammatory disorders, particularly in COPD, a serious respiratory disorder with major unmet medical need. In preclinical models, ELB353 demonstrated a broader therapeutic window than other PDE-4 inhibitors and was free of central nervous system related side effects at therapeutically relevant doses. This is likely due to hepatic conversion of ELB353 to a major active metabolite which exhibits low brain penetration.
About Biotie Therapies
Biotie is a drug discovery and development company focused on central nervous system and inflammatory diseases. It has a broad range of innovative small molecule and biological drug candidates at different stages of clinical and pre-clinical development. Biotie’s products address diseases with high unmet medical need and significant market potential, including addiction and psychotic disorders, rheumatoid arthritis, psoriasis and chronic obstructive pulmonary disease (COPD). The most advanced product, nalmefene for alcohol dependence, is currently in phase III clinical development by licensing partner H. Lundbeck A/S.
The commercial value of the pipeline has been demonstrated through existing alliances with top-tier global pharmaceutical companies such as Lundbeck, Roche and Pfizer. Biotie has operations in Turku, Finland and Radebeul, Germany. Biotie shares are listed on NASDAQ OMX Helsinki Ltd.
