Wednesday, June 18, 2014: HMP today announces that it has initiated the first-in-human Phase I clinical trial of HMPL-523 in Australia. HMPL-523 is a novel, highly selective and potent small molecule inhibitor targeting spleen tyrosine kinase, also known as Syk, a key component in B-cell receptor signaling. HMPL-523 is HMP’s second active immunology program in clinical development. The first drug dose was administered on June 17, 2014.
As one of the major cellular components of the immune system, B-cells play pivotal roles in autoimmune diseases. Targeted B-cell receptor signaling therapy has been proven to be clinically effective for the treatment of rheumatoid arthritis (“RA”) and B-cell malignancies, leading to scientific and commercial success. Syk is an essential enzyme involved in B-cell receptor signaling pathway and a novel target for investigational therapies in immunology and oncology.
HMPL-523 is being developed as an oral formulation for the treatment of autoimmune diseases such as RA and lupus. In preclinical studies, HMPL-523 demonstrated superior potency and kinase selectivity, a reversal of the progression of joint inflammation and bone erosion along with a reduced production of multiple pro-inflammatory cytokines, as well as a favorable safety margin in both rodent and non-rodent toxicology studies.
The first-in-human trial aims to establish the safety profile of HMPL-523. This randomized, double blind, placebo-controlled, dose-escalating study of the safety, tolerability and pharmacokinetics of single and repeat doses of HMPL-523 will be conducted in healthy volunteers. Initial results are expected around the end of this year.
“For these chronic inflammatory conditions, it is critically important to understand if the high Syk selectivity and very good pharmacokinetic properties of HMPL-523 in preclinical studies bear out into a good human safety profile,” said Christian Hogg, CEO of HMP’s majority shareholder Chi-Med. “Should this be proven in this Phase I trial, this drug candidate will have potential as an effective oral treatment for patients with debilitating autoimmune diseases, for whom many existing treatments are limited or only modestly efficacious at safe doses,” he added.
About rheumatoid arthritis
Rheumatoid arthritis (“RA”) is an autoimmune disease that affects many tissues and organs, but principally attacks flexible joints. Treatment of RA includes both painkillers and anti-inflammatory drugs, such as steroids, which relieve the symptoms but do not stop or slow down the disease progression. Disease-modifying anti-rheumatic drugs (DMARDs), including TNF-blocking biologics, are able to slow or halt the disease progression. The market for RA drugs is predicted to reach US$38.5 billion in 2017, according to Visiongain.
Lupus, or systemic lupus erythematous, is a systemic autoimmune disease that can affect any part of the body, particularly the heart, joints, skin, lungs, blood vessels, liver, kidney, and nervous system. Lupus can be fatal, and there is currently no cure for lupus. Patients with mild lupus are often prescribed with non-steroidal anti-inflammatory drugs (“NSAIDs”) while patients with more severe lupus may require corticosteroids or immunosuppressants.