Gan & Lee Pharma Unveils Positive Weekly Insulin GZR4 Results at EASD 2024

Gan & Lee Pharmaceuticals has unveiled the clinical outcomes from two Phase I trials of their novel once-weekly insulin analog, GZR4. These results were presented at the 60th Annual Meeting of the European Association for the Study of Diabetes (EASD 2024). The trials assessed the safety, tolerability, and efficacy of GZR4 in both healthy individuals and patients with Type 2 diabetes mellitus (T2DM).

The Phase Ia study was a randomized, placebo-controlled, and active-comparator-controlled trial conducted at a single center. The study involved a single dose of GZR4 administered subcutaneously to healthy adult male participants. The dose-escalation design began with lower doses and increased progressively. Cohorts 1-4 received GZR4 doses ranging from 1 to 12 nmol/kg, while cohort 5 received 0.4 U/kg of insulin degludec (IDeg) as an active comparator. A glucose clamp procedure was performed on days 2 and 7 post-GZR4 administration for cohorts 2-4, and on day 1 for cohort 5.

The results demonstrated that GZR4 had a favorable safety and tolerability profile among healthy subjects, with no serious adverse events reported. The pharmacodynamic results showed that the glucose-lowering effect of GZR4 persisted for up to one week, as indicated by the glucose infusion rate (GIR). On day 7, the GIR was about 80% of that on day 2 for the 12 nmol/kg dose group. Additionally, the area under the GIR-time curve for the 6 nmol/kg dose of GZR4 was comparable to that of IDeg, suggesting that GZR4 has a similar glucose-lowering effect to IDeg at a 2.5-fold greater potency.

The Phase Ib study was a randomized, open-label, active-controlled, multi-center trial involving 36 T2DM patients previously treated with basal insulin. Participants were divided into groups receiving either a fixed once-weekly dose of GZR4 (6, 8, or 12 nmol/kg) or once-daily IDeg for six weeks.

Pharmacokinetic data indicated a dose-dependent increase in the maximum plasma concentration (Cmax) of GZR4, with a time to maximum concentration (Tmax) of approximately 32 hours and a half-life of around 135 hours at steady state. Pharmacodynamic data showed that GZR4 led to dose-dependent reductions in fasting blood glucose (FBG) levels by week 6, outperforming the IDeg group. Specifically, the 6 nmol/kg GZR4 group exhibited an HbA1c reduction of 0.76%, compared to just 0.13% in the IDeg group.

Throughout the Phase Ib study, GZR4 was safe and well-tolerated, with no serious adverse events. The most commonly reported side effect was hypoglycemia, though no severe cases occurred.

Gan & Lee Pharmaceuticals also announced the commencement of a multicenter, randomized, open-label Phase 2 study, aimed at evaluating the efficacy and safety of once-weekly GZR4 in T2DM patients inadequately controlled with oral antidiabetic drugs. The study includes insulin-naïve patients and those on basal insulin. With 179 participants, preliminary results have been promising, further supporting the Phase I findings.

Dr. Gan Zhong-ru, Chairman of Gan & Lee Pharmaceuticals, highlighted the potential of weekly insulin preparations like GZR4 to improve patient adherence and glycemic control. He noted that the Phase I trials confirm GZR4’s capability to maintain stable blood sugar levels for a week with a single dose, while also reducing the required weekly insulin dosage and the risk of hypoglycemia.

Gan & Lee Pharmaceuticals is committed to expanding its insulin product portfolio and enhancing its presence in both domestic and international markets. The company aims to develop new treatments for metabolic and cardiovascular diseases, reinforcing its mission to become a world-class pharmaceutical entity.