REMD Biotherapeutics’ Phase II study of volagidemab has revealed improvements in glycemic control. The results revealed that volagidemab was associated with meaningful improvements in glycemic control, measured by haemoglobin A1c (HbA1c) and CGM parameters, in type 1 diabetes (T1D) patients after 12 weeks of treatment.
While full results have not yet been announced, the Phase I trial indicated that patients were able to reduce daily insulin use by 26% (12 units). Participants received CGM for eight weeks after inpatient observation, and the average daily glucose assessed by CGM was 20–31mg / dL lower in volagidemab-treated patients compared with the placebo arm. Given the long-acting nature and persistent blood concentrations of volagidemab, it is likely that patients may be dosed once per week.
The study enrolled around 150 patients across 11 clinical sites in the US. The study consisted of two parts. Part A included unblinded continuous glucose monitoring (CGM) and inpatient stays, and Part B included blinded CGM and no inpatient stays. The study aimed to determine whether volagidemab could decrease daily insulin requirements and improve glycemic control after 12 weeks of treatment in subjects diagnosed with T1D with an initial fasting C-peptide of less than 0.7ng / mL.
The topline results are promising because their potential impacts on lowering blood glucose levels, reducing patient insulin dose requirements and reducing the risk of complications will be imperative for T1D disease management.
Experts interviewed by GlobalData stressed the importance of glycemic control in managing T1D, as only about 20–30% of T1D patients meet their glycemic targets, putting them at greater risk of metabolic syndrome and other complications.
The results do not include information about volagidemab’s impact on weight loss, which is a large unmet need in diabetes. GlobalData’s Epidemiology forecasts have found that 47% of T1D patients are overweight or obese, so weight loss will be a critical benchmark for volagidemab to meet. It is not known if this will be investigated in future trials.
Volagidemab is an injectable, which will make it difficult to penetrate the adjunct therapeutic market in a T1D patient population currently overwhelmed by injectable insulin treatments. Volagidemab will need to be affordable, assist with glycemic control (as adjunctive therapy to insulin), and confer weight loss in order for physicians to justify prescribing yet another injectable therapeutic and allow volagidemab to compete against the oral TTP-399, which has a similar glycemic impact.
GlobalData expects that REMD Biotherapeutics will focus on the US market, as SGLT inhibitors are not approved in the US, providing the company with an accessible market for its potential weekly injectable.
Currently, AstraZeneca’s Symlin (pramlintide) is the only approved adjunct therapeutic in the US for T1D. The T1D markets in Europe and Japan also include two sodium-glucose linked transporter (SGLT) inhibitors each. In Europe, AstraZeneca’s Forxiga (dapagliflozin) and Lexicon Therapeutics’ Zynquista (sotagliflozin) have been approved, while Forxiga and Astellas’ Suglat (ipragliflozin) have been approved in Japan. In the pipeline, vTv Therapeutics’ TTP399, an oral liver-selective glucokinase activator, has also been shown to improve HbA1c, reduce insulin doses, and not increase the risk of hypoglycemia or diabetic ketoacidosis.
Volagidemab, originally developed by Amgen, is a human monoclonal antibody that functions as a glucagon receptor agonist. In May 2013, REMD Biotherapeutics licensed volagidemab from Amgen for research and clinical development.