Hanmi, LG Highlight Diabetes Pipeline Progress At EASD
This article was originally published in PharmAsia News
Executive Summary
South Korea’s Hanmi Pharmaceutical and LG Life Sciences presented progress across their diabetes pipelines at the recent annual EASD meeting, with both firms unveiling promising results from a range of studies.
SEOUL – Hanmi Pharmaceutical Co. Ltd. unveiled clinical progress in its Quantum Project, taking a step closer to developing long-acting diabetes and obesity therapies, while LG Life Sciences Ltd. released new clinical data for Zemiglo (gemigliptin) at the recent annual meeting of the European Association for the Study of Diabetes (EASD) held in Stockholm.
Hanmi’s Quantum Project includes efpeglenatide (HM11260C, long-acting Exendin-4 analog), LAPS Insulin 115 (HM12470, long-acting insulin analog) and LAPS Insulin Combo (long-acting Insulin 115/Exendin-4 combination). The final result of a Phase IIb study for efpeglenatide, the only once-a-month therapy among GLP-1 diabetes therapies at present, has reaffirmed its potential in this dosing regimen, Hanmi said.
A total of 209 subjects with type 2 diabetes were administered 8mg, 12mg or 16mg of efpeglenatide for 16 weeks and all showed improvement in glycemic control, with HbA1c falling to 7% or below, and had reduced weight when compared to placebo.
Hanmi also presented a Phase IIb study of efpeglenatide as a weekly treatment and in obesity patients without diabetes. In the once-a-week formulation study, glucose levels and body weight of the subjects dropped after administration of 3mg and 4mg of efpeglenatide, with a total of 254 subjects with type 2 diabetes participating in the trial.
In a study in 297 obesity patients without diabetes, the subjects were administered 4mg and 6mg of efpeglenatide once a week, and 6mg and 8mg of efpeglenatide once every two weeks. The study confirmed safety and outstanding weight reduction effect compared to placebo, the firm said.
LAPS Promise
In addition, Hanmi released the outcome of preclinical trials for LAPS Insulin 115 and LAPS Insulin Combo. At present, the company is conducting a Phase I study of LAPS Insulin115 in the US and has finished a preclinical study of the LAPS Insulin Combo. It is designing a Phase I study which could take place in South Korea or multiple countries, said a Hanmi official.
The study of LAPS Insulin 115 confirmed its potential development as a long-acting insulin which has lowered dosage volume by controlling binding of insulin receptors versus existing insulin products in animal tests. LAPS Insulin Combo, which is a combination of efpeglenatide and LAPS Insulin, is a first-in-class, once-a-week diabetes therapy.
When compared to individual therapy of efpeglenatide and LAPS Insulin, LAPS Insulin Combo has shown outstanding effects in reducing glucose levels, curbing weight increase and preserving beta cells that play a part in secretion of insulin, the firm said.
The results of Hanmi’s key Quantum Project were also presented at the annual meeting of American Diabetes Association in June.
Analysts have estimated that the Quantum Project, if Hanmi successfully inks a licensing out agreement for its diabetes candidates, could exceed the value of its recent big licensing deals with Eli Lilly & Co. (Also see "Lilly Signs Major Collaboration With Hanmi For RA Drug" - Scrip, 20 Mar, 2015.) and Boehringer Ingelheim GMBH (Also see "Hanmi Inks Record Korean Deal, With Boehringer For Cancer Therapy" - Scrip, 28 Jul, 2015.).
LG’s Gemigliptin
Separately, LG Life Science held a symposium during the EASD meeting and presented several studies that have shown improvement in glycemic variability and kidney protection effect for its diabetes therapy Zemiglo (gemigliptin), a dipeptidyl peptidase-4 (DPP-4) inhibitor.
In a study to assess the effects of gemigliptin versus sitagliptin or glimepiride on glycemic variability, the company said gemigliptin was more effective than glimepiride and sitagliptin in reducing glucose variability as initial combination therapy with metformin in drug-naive patients with Type 2 diabetes.
A multicenter, open-label, parallel design study was performed in 69 patients with HbA1c greater than 7.5%, in which subjects were randomized (1:1:1)to receive gemigliptin 50mg, sitagliptin 100mg, or glimepiride 2mg pre day for 12 weeks.
A greater decrease in total and LDL-cholesterol and nitrotyrosine was observed for the DPP-4 inhibitor groups versus glimepiride, although there were no significant differences between the groups. In addition, only gemigliptin significantly decreased C-reactive protein levels from baseline. Drug-related adverse events including symptomatic hypoglycemia were reported more frequently in glimepiride group than in other groups.
In a study to evaluate the efficacy and safety of gemigliptin in type 2 diabetes patients with moderate to severe renal impairment, the company said gemigliptin improved glycemic control and provided additional renoprotection in these patients. There was no additional risk of hypoglycemia and no weight gain.
The randomized, double blind, parallel group Phase IIIb study comprised a 12-week, placebo controlled phase followed by a 40-week, double blind active-controlled extension phase (placebo switched to linagliptin).
Another study evaluated the efficacy of gemigliptin on retinal vascular leakage in db/db mice, an animal model for type 2 diabetes and neovascularization in oxygen-induced retinopathy mice, an animal model for ischemic proliferative retinopathy.
The result suggested that gemigliptin has a potent anti-angiogenic activity via its ability to inhibit the pro-angiogenic PAI-1-related signaling pathway and support the direct retinoprotective action of gemigliptin.
Export Plans
LG Life, which launched Zemiglo in South Korea in 2012, plans to export the drug to 105 countries through its partners including Sanofi and Stendhal.
DPP-4 inhibitors, which are used as second- or third-line therapies for patients with type 2 diabetes, have relatively fewer side effects, can be cheaper than other new therapies, and are administered orally. Zemiglo was launched as the fifth DPP-4 inhibitor in South Korea, where the competitive sector is expected to see about nine products vying by the end of this year, according to Samsung Securities.
The brokerage noted that price and marketing strategies will be crucial in differentiating DPP-4 inhibitors as otherwise there aren’t sharp differences in their functions and side effects.