medwireNews: Add-on treatment with the glucagon receptor antagonist volagidemab may improve glycemic control in people with type 1 diabetes, suggest phase 2 study results.
Speaking at the virtual ADA 81st Scientific Sessions, Jeremy Pettus (University of California, San Diego, USA) explained that the “paradoxical spike” in glucagon levels following glucose challenge contributes to impaired glycemic control in type 1 diabetes, and previous study results showed that a single injection of volagidemab (previously known as REMD-477) decreased insulin requirement and average glucose levels.
The phase 2 study included two trials. In the first, 75 participants with glycated hemoglobin (HbA1c) levels below 10% (86 mmol/mol) underwent unblinded continuous glucose monitoring (CGM), while in the second, 78 participants with HbA1c levels below 10% but above 7% (53 mmol/mol) underwent blinded GCM. People in both trials were randomly assigned to receive once-weekly subcutaneous injections with volagidemab 35 mg, volagidemab 70 mg, or placebo for 12 weeks in addition to continued insulin treatment.
In trial 1, Pettus reported numerically greater reductions in HbA1c from baseline to week 12 among participants treated with volagidemab 35 mg or 70 mg versus placebo, with decreases of 0.67% and 0.66%, respectively, versus 0.43%. Baseline values ranged from 7.42% to 7.58% (58–59 mmol/mol).
There was a similar pattern of results in trial 2, with reductions of 0.64% and 0.60%, respectively, versus 0.11%, from baseline values of 7.74–8.05% (61–64 mmol/mol), with significantly greater decreases among participants treated with either dose of volagidemab compared with placebo.
The presenter said that volagidemab also increased the proportion of participants who achieved target HbA1c levels below 7%, with rates of 58% and 59% for the 35 mg and 70 mg doses, respectively, compared with 28% in the placebo group when data from both trials were combined.
Rates of treatment-emergent adverse events were comparable in the 35 mg, 70 mg, and placebo arms, at 74.5%, 70.6%, and 76.9%, respectively. However, volagidemab-treated individuals were more likely to experience increases in alanine aminotransferase and blood pressure than those in the placebo arm, which Pettus said returned to baseline after treatment discontinuation.
Adverse events of hypoglycemia were reported in 7.8%, 2.0%, and 9.6% of people in the 35 mg, 70 mg, and placebo arms, respectively. The presenter noted that participants in all groups experienced a reduction in the overall proportion of time spent in hypoglycemia in trial 1, whereas there was a “slight increase” with the higher volagidemab dose in trial 2.
Pettus concluded that these findings support further development of volagidemab for type 1 diabetes, and announced that the 35 mg dose will progress into phase 3 trials because it gave rise to “equivalent HbA1c reductions” compared with the higher dose, without a potential signal for hypoglycemia.
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