Phase I Trial of Lupus Oral Inhibitor Meets Safety, Tolerability Targets

Hutchison China MediTech Limited (Chi-Med) recently announced that its R&D subsidiary Hutchison MediPharma (HMP) has completed its Phase I study of HMPL-523, a potential global first-in-class oral inhibitor targeting the spleen tyrosine kinase Syk, a key protein involved in B-cell signaling. Modulation of the B-cell signaling pathway has proven to significantly advance treatment of certain chronic immune diseases, such as lupus and rheumatoid arthritis.

The Phase I clinical trial evaluating the drug agent was a dose-escalating study that assessed the tolerability, safety, and pharmacokinetics of both single and repeat HMPL-523 doses in healthy Australian volunteers. The trial, which began in June 2014, successfully completed 10 single dose clinical groups ( eight participants per group) of 5mg through 800mg single dose. The multiple ascending dose section of the study began in April, with HMPL-523 administered to study participants once daily for a period of 14 consecutive days.

This section has now completed four dose cohorts, again with eight participants per cohort, from a multiple dose of 200mg through to 400mg.  At 400mg per day, drug exposures are thought to be above the expected efficacious dose level, and no further dosage escalation is intended in healthy participants.

The preliminary safety profile of HMPL-523 was reported to be in line with the company’s predictions, with HMPL-523 found not to cause off-target toxicities, including hypertension and severe diarrhea. In terms of pharmacokinetics, the drug agent was found to have a linear pharmacokinetic profile and a dose dependent suppression of B-cell activation.  The company expects to announce the full results soon.

“We have now established what we believe is a dose range for the further development of HMPL-523. This will now allow Chi-Med to move this important, potentially first-in-class compound into global Phase II proof-of-concept studies against multiple indications both in autoimmune diseases and oncology,” said Christian Hogg, CEO of Chi-Med, in a press release.