Following up on its impressive Phase 1a trial data presented at last year's American Diabetes Association conference, Hua Medicine, an innovative, clinical-stage biotechnology company in Shanghai, announced positive results from its recently completed multicenter, multi-dose Phase 1b Trial in Diabetes. HMS5552 (also known as sinogliatin) is a novel 4th-Generation glucokinase activator (GKA) for Type 2 Diabetes which demonstrated excellent 24-hour glucose control of both fasting plasma glucose (FPG) and post-meal glucose (PMG) levels in diabetic patients. In addition, sinogliatin showed robust glucose-stimulated insulin release (GSIR), and sustained dose-proportional glucose lowering with very low risk of hypoglycemia throughout the trial. The Phase 1a clinical data were previously presented at the 74th American Diabetes Association Conference in San Francisco in June 2014, while these current Phase 1b trial results will also shortly be submitted for publication.
"In addition to the excellent pharmokinetic and safety profile demonstrated in this trial, we are very excited by sinogliatin's potential to control glucose all-day in diabetic patients with only a single oral agent. Most oral diabetes therapies primarily can control either a patient's fasting glucose (for example, using metformin) or their post-meal glucose levels. However, few can safely provide both FPG and PMG, 24-hour control in a single agent, and that's what makes these results with sinogliatin so unique," stated Hua Medicine's Head of Clinical Development, Dr. Yi Zhang.
"It's important to realize how difficult it is for most diabetes patients to control their blood glucose levels throughout the entire day whether working, eating, or sleeping," said Dr. John Baldwin, Chair of Hua Medicine's Portfolio Advisory Board. "Diabetes is a scourge affecting over 380 million patients world-wide, and over 100 million in China alone. If left untreated, diabetes leads to devastating consequences including heart disease, nerve damage, kidney failure and blindness. Therefore, developing a therapy such as sinogliatin that can help patients maintain 24-hour glucose control is critical."
The Phase 1b study of sinogliatin was a randomized, double-blind, placebo-controlled, multiple ascending dose study in 53 diabetic patients. The study was designed to assess the safety, tolerability, PK/PD, and preliminary efficacy of the drug. Sinogliatin was evaluated in five ascending doses ranging from 25, 50, 100, 150 and 200 mg, with each dose group having 9-12 randomized patients per group (2 placebo, 7-10 on drug) and receiving multiple oral doses during the 8-day treatment period. The trial demonstrated:
-Safety & Tolerability: excellent safety profile with low risk of hypoglycemia. Sinogliatin was well tolerated for all doses up to the maximum tolerated dose (MTD) of 200 mg. All adverse events (AE) were mild with no severe AEs, deaths, or any significant laboratory, lipids, vital sign, or ECG abnormalities
-Pharmacokinetics: excellent linear correlation between drug dose and plasma exposure, dose-proportional AUC and Cmax across all 5 dose groups, no apparent food effect on PK, or PK gender differences between male and female subjects, no drug accumulation, and no major metabolites were seen in plasma on all tested dose groups
-Pharmacodynamics & Efficacy: dose proportional decreases in FPG, PMG and 24-hour glucose levels with low risk of hypoglycemia. Robust and dose proportional increases in post-meal C-peptide and insulin without increasing pre-meal insulin levels, validating the glucose-sensing selectivity of sinogliatin
"We are very gratified with the clinical results of sinogliatin (HMS5552). Earlier generations of GKAs entering into clinical studies have suffered from significant alternations in glucose-sensing enzyme kinetics and from unexpected human metabolites that impacted safety and efficacy. Comparatively, sinogiatin's chemistry was specifically engineered to more closely follow the natural GK enzyme's kinetic properties in order to eliminate these negative effects, and has robustly demonstrated all the desirable properties that support its development into a novel oral medicine for T2D patients," explained Dr. Li Chen, CEO of Hua Medicine. "Additionally, HMS5552 generates no major metabolites in humans nor in the multiple animal species tested, which leads to excellent correlations in the PK/PD results generated between animal and human subjects. This further decreases the uncertainty in future human clinical studies, increasing the chance of success in Phase 2 and 3 trials."
"Hua Medicine recently closed a $25 million Series B financing round in January in order to initiate Phase 2 trials for this very promising diabetes therapy," said Daniel Auerbach, Managing Partner of Fidelity Growth Partners Asia. "These excellent clinical data validate our confidence in the therapeutic potential of sinogliatin, and we are very pleased to help the company make further progress on its pipeline."
After China's CFDA regulatory agency completes its review of both the Phase 1a and Phase 1b results, the company will initiate a multicenter Phase 2 trial in diabetic patients that is expected to complete patient enrollment by YE 2015, with topline results available by 2Q2016. Concurrently, the company is filing a US IND this quarter, and will complete Phase 1 trials in the US by YE 2015. The Phase 2 multi-center trial in China will be a 12-week, randomized, double-blind, placebo-controlled trial in approximately 280 diabetic adult male and female patients. In addition to evaluating sinogliatin's safety and efficacy (as determined by HbA1c lowering at the end of 12-weeks), the trial will evaluate potential improvements in associated hormones and biomarkers of beta-cell health. These results are expected to further support sinogliatin's novel mechanism of action and give guidance for trial design and optimal patient selection in future Phase 3 trials.
About Hua Medicine
Hua is a leading, innovative drug development company in China focused on novel therapies for the treatment of diabetes and CNS disorders. Founded by an experienced group of entrepreneurs and international investment firms, Hua currently has world-wide rights to two novel assets. The most advanced program is a first-in-class, oral drug for the treatment of Type 2 Diabetes that will shortly initiate Phase 2 trials in China. The company has also internally developed earlier-stage compounds focused on a highly validated CNS target for multiple indications including Parkinson's Disease associated dyskinesia and Depressive Disorder. Hua's strategy is to leverage the cost-efficient and high-quality drug discovery capabilities available in China, while partnering or licensing the most promising drug assets from the US and abroad. Through these efforts, Hua intends to be the driving force behind China's evolution into a global innovation center for drug development. For more information: www.huamedicine.com