Phase 1 trial results of an investigative selective inhibitor drug demonstrated that single or multiple oral doses of the therapy are safe and well tolerated by healthy subjects.
These results may prompted for future Phase 2 clinical studies of HMPL-523 for the treatment of autoimmune diseases, including rheumatoid arthritis.
The drug HMPL-523, developed by Hutchison China MediTech Limited (Chi-Med), is a highly selective oral inhibitor that targets the enzyme Syk (spleen tyrosine kinase). Syk is a key player in the immune response of B-cells, which has been proven to be beneficial in chronic immune diseases such as rheumatoid arthritis.
Scientists had been unable to develop inhibitors targeting Syk that could be approved to treat chronic immune diseases. This was largely due to severe off-target side effects and elevated toxicity. HMPL-523 was specifically designed to overcome these toxicity issues.
Also, this new drug structure allows it to be easily cleared from the system, reducing the risk of infection due to its inhibitory effects on immune cells.
The Phase 1 clinical trial of HMPL-523 (NCT02105129) assessed the safety and tolerability of the drug in healthy male volunteers. A total of 118 healthy adult men were enrolled who were given different dosages of HMPL-523, up to a maximum of 800 mg, or a placebo control.
A total of 83 treatment emergent adverse events (TEAEs) were reported during the study, of which 38.9% were in the HMPL-523 group and 32.1% were in the placebo group. The majority of TEAEs were mild events and only two serious adverse events were reported. The overall results demonstrated the low toxicity and safety of HMPL-523.
These results were recently presented at the American College of Rheumatology (ACR)/Association of Rheumatology Health Professionals (ARHP) Annual Meeting, in a poster presentation titled “A Phase I, Randomized, Double Blind, Placebo-Controlled, Dose Escalating Study of the Safety, Tolerability and Pharmacokinetics and Pharmacodynamics of Single and Multiple Doses of Hmpl‑523 in Australian Male Healthy Subjects.”
“Overall, the safety and laboratory data suggests that the single and multiple doses of HPML-523 were generally well tolerated. A multiple-dose regimen of 300 mg or less of HMPL-523, administered once daily, is recommended for future Phase II clinical trials for autoimmune diseases,” the authors wrote.