Hua Medicine of Shanghai announced positive results from a China Phase Ib trial of HMS5552 (sinogliatin) among patients with diabetes. The molecule is a novel oral 4th-generation glucokinase activator (GKA) for Type 2 diabetes that Hua in-licensed from Roche (SIX: ROG) in 2011 (see story). In the trial, sinogliatin provided patients with 24-hour glucose control of both fasting plasma glucose (FPG) and post-meal glucose (PMG) levels, something that usually requires two separate drugs. Hua expects to start a China Phase II trial and to complete a US Phase I trial of sinogliatin in 2015.

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. There were no serious adverse effects from the drug in the trial. Earlier versions of GKA drugs successfully lowered blood glucose, but they also caused side effects, especially hypoglycemia.

In January, Hua closed a $25 million Series B financing that will underwrite the China Phase II clinical trial of sinogliatin and the Phase I trial in the US (see story). 

Previously, Hua reported positive data from a Phase Ia trial of the drug. Data from that trial was presented at the 2014 American Diabetes Association conference,

“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,” said 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,” added 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. Hua presented an early description of the results:

• Safety & Tolerability: an 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, sinogliatin'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,” he added.  

Hua has submitted the data from its two Phase I trials to the CFDA for review. It expects to be granted a green light on the Phase II trial in enough time to complete patient enrollment of 280 patients by the end of this year. Top-line data from the 12-week trial will be available in 2Q2016. 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, which Hua hopes will give proof-of-concept for sinogliatin’s novel mechanism of action.

Hua Medicine, which started its corporate existence with a $50 million funding, was co-founded by Dr. Ge Li, the CEO of WuXi PharmaTech (NYSE: WX) and WuXi participated in the first funding round.

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Disclosure: none.