Hutchison MediPharma Limited (HMP) released the outcome of its Phase I clinical trial of HMPL-523. The first-in-human study was a dose-escalating trial to assess the safety, tolerability, and side effects of single and multiple doses of HPML-523, a potent small molecule inhibitor that targets spleen tyrosine kinase, also known as Syk, a crucial component in B-cell receptor signaling.
The study began in June 2014 in healthy volunteers in Australia with single dose cohorts. In April 2015, the multiple ascending dose cohort began. With eight patients per cohort, the dosage varied from 5mg to 800mg single dose, and from 200mg to 400mg multiple dose. This study concluded that at 400mg a day the drug is believed to be above its efficacious point, and no further escalation would be done in a healthy study population.
This initial research phase found no off-target toxicities, like hypertension or severe diarrhea. HMPL-523 showed a linear pharmacokinetic profile and predictable supression of B-cell activation, depending on dosage, and full study results will be published 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,” Christian Hogg, CEO of Chi-Med, said in a news release.
HMP is the drug R&D subsidiary of Hutchison China MediTech Limited, or Chi-Med.
More about HMPL–523
B-cells are at the epicenter of several immune system-related diseases, like the autoimmune diseases rheumatoid arthritis and systemic lupus, as well as hematological cancers — also known as B-cell malignancies — including lymphoma and leukemia. Similar targeted B-cell receptor signaling therapies have already proven to be efficient when fighting rheumatoid arthritis (RA) as well as B-cell malignancies.
HMPL-523 targets Syk (spleen tyrosine kinase) in an oral small molecule therapy. The authors of this research believe that, if proven safe and effective, HMPL-523 can become an attractive therapy in comparison to other intravenous B-cell receptor blocking drugs. The authors further claim that oral small molecules are not only more convenient for the patient, but also easier to process by the human body, reducing the risk of infections.
Investigators believe HMPL-523 has shown the potential for positive effects on tissue-oriented autoimmune diseases, with research results displaying relevant effects in RA and lupus pre-clinical models with relatively low plasma concentrations. Therefore, this study will evaluate HMPL-523 as a treatment for lupus in addition to the already planned global Phase II development in RA. Furthermore, as B-cell receptor signaling therapy has proven its advantages in hematological cancers as well, the investigators intend to initiate a Phase I trial hematological cancer patients in Australia in late 2015.