Survodutide, Formerly BI 456906, Impresses in Phase 2 Dose-Finding Trial

Article

Data from a phase 2 dose-finding trial from ADA 2023 suggests use of survodutide was associated with a mean body weight reduction of 14.9% at 46 weeks, with 67% of people using survodutide 4.8 mg losing 15% or more of their baseline body weight.

Carel Le Roux, MD, PhD | Credit: Twitter

Carel Le Roux, MD, PhD
Credit: Twitter

New data from the 83rd Scientific Sessions of the American Diabetes Association (ADA 2023) suggests use of survodutide, formerly known as BI 456906, was associated with a mean body weight reduction of 14.9%, with more than 65% of those receiving the 4.8 mg dose experiencing body weight reductions of 15% or greater.

A glucagon/GLP-1 receptor dual agonist being developed through a collaborative partnership between Boehringer Ingelheim and Zealand Pharma, results of the phase 2 trial offer insight into the effects of 4 doses of survodutide administered over a 46-week treatment course in people with overweight or obesity without type 2 diabetes.

“Given the prevalence of obesity and its many disease-related complications, there is a dire need for treatments that can help treat the disease of obesity effectively,” said principal investigator Carel le Roux, MD, PhD, professor at University College in Dublin, Ireland. “Current treatments for obesity mainly focus on weight loss by reducing energy intake. By activating both the glucagon and GLP-1 receptors, survodutide may both inhibit appetite and improve energy expenditure, thereby helping to treat the disease of obesity. These encouraging data support the further study of survodutide in larger Phase III trials.”

Although the phase 2 trial was presented on the first day of ADA 2023, the community had looked forward with anticipation of the data since Boehringer Ingelheim and Zealand Pharma announced topline data in May 2023. Designed as a randomized, double-blind, parallel-group, dose-finding study, the phase 2 trial enrolled a population of 387 and randomized them in a 1:1:1:1:1 ratio to weekly subcutaneous survodutide in 0.6 mg, 2.4 mg, 3.6 mg, or 4.8 mg dose or placebo therapy.

Per trial protocol, the first 20 weeks of treatment were a dose-escalating phase, with bi-weekly dose escalation, which was followed by a 26-week maintenance period. The primary outcome of interest for the study was the percent of body weight change from baseline to week 46. Secondary outcomes of interest for the study include the proportion of patients achieving 5% or more, 10% or more, and 15% or more of total body weight loss at week 46.1

Of the 387 patients who underwent randomization, 384 were included in the full analysis set. At baseline, those included in the full analysis set had a mean age of 49.1 years, mean body weight of 105.7 kg, mean BMI of 37.1 kg/m2, and 31.8% were male.1

Upon analysis, results indicated use of survodutide provided benefit in a non-flat dose response curve of body weight change from baseline to week 46. The mean body weight reduction over 46 weeks of the study were -6.2% with 0.6 mg survodutide, -12.5% with 2.4 mg survodutide, -13.2% with 3.6 mg survodutide, -14.9% with 4.8 mg survodutide, and -2.8% with placebo therapy.1

Analysis of secondary outcomes of interest suggested the weight loss threshold of 5% or more, 10% or more, and 15% or more were achieved by 82.8%, 68.8%, and 54.7% of 4.8 mg survodutide groups compared to 25.9%, 11.1%, and 5.6% of those receiving placebo therapy. Investigators highlighted the mean body weight loss at 46 weeks achieved by those reaching and staying on 4.8 mg survodutide was 18.7%.1

When assessing safety outcomes, results of the study suggested adverse events occurred among 90.9% of those randomized to survodutide and 75.3% of those receiving placebo therapy, with most of these events being gastrointestinal in nature. Investigators pointed out the rate of discontinuation was 24.6% with survodutide and 3.9% with placebo therapy, with the majority of those discontinuing survodutide doing so during dose escalation.1

“With our long heritage in researching and developing new treatments for cardiovascular, renal, and metabolic conditions, we are extremely encouraged by these robust and compelling Phase II data,” said Carinne Brouillon, head of Human Pharma with Boehringer Ingelheim.2 “Survodutide may become the first anti-obesity medication to reduce appetite while increasing energy expenditure through the liver. We look forward to furthering our discussions with health authorities to advance this dual receptor agonist into Phase III trials as we aim to help fill a treatment gap in this disease area.”

In addition to examining the agent in obesity management, Boehringer Ingelheim and Zealand Pharma are also evaluating survodutide in a phase II study in adults with NASH and liver fibrosis, with this trial expected to be completed prior to the end of 2023.3

References:

  1. Le Roux CW, Steen O, Lucas KJ, et al. A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Dose-Finding Study of BI 456906 in People with Overweight/Obesity. Paper presented at: the 83rd Scientific Sessions of the American Diabetes Association. June 23 – 26, 2023.
  2. Data shows nearly 19% weight loss in people with overweight or obesity in Boehringer Ingelheim and Zealand Pharma Phase II trial with survodutide (BI 456906). Boehringer Ingelheim. June 23, 2023. Accessed June 23, 2023. https://www.boehringer-ingelheim.com/human-health/metabolic-diseases/obesity/phase-ii-clinical-trial-weight-loss-results.
  3. Campbell P. Bi 456906 shows promise, reducing body weight up to 14.9%, in phase 2 trial. HCP Live. May 10, 2023. Accessed June 23, 2023. https://www.hcplive.com/view/bi-456906-shows-promise-reducing-body-weight-in-phase-2-trial.
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