A Novartis investigational product called Bimagrumab recently raised attention in the obesity research community. The human monoclonal antibody was designed to treat muscle loss and weakness but unfortunately failed in Phase 2b/3 clinical trials testing for sporadic inclusion body myositis. By 2019, the sponsor verified the investigational product could target obesity. Now, recent study results reveal the experimental antibody may provide a novel pharmacologic approach for managing patients with type 2 diabetes and excess adiposity.
This recent Phase 2 clinical trial (NCT03005288) was formally called “A Randomized, Subject-and Investigator-blinded, Placebo Controlled Study to Assess the Safety, Pharmacokinetics and Efficacy of Intravenous Bimagrumab in Overweight and Obese Patients with Type 2 Diabetes.”
This non-confirmatory study investigated a 48-week treatment the investigational drug and included two (2) treatment arms in a ration of 1:1 including 1) Bimagrumab 10 mg/kg up to maximum 1200 mg, every 4 weeks (12 doses) till week 44 and 2) Placebo every 4 weeks (12 doses) till week 44. The study consisted of a screening baseline of 3 weeks, 48 week treatment period and final follow-up period taking 8 weeks. The sponsor set up visits with the patient every 4 weeks till week 44. The investigators administered the drug via infusion over 30 minutes followed by flushing 15 minutes as described in the sponsor’s clincialtrials.gov disclosure. During visits the investigator and staff evaluated for safety, tolerability, PK and efficacy.
The study’s primary endpoint involved measuring a change from baseline total body fat mass by dual energy X-ray absorptiometry (DXA) at study week 48. The study involved several secondary endpoint measures.
According to a recent Obese Society press release, a total of 75 patients with type 2 diabetes, body mass index between 28 and 40 and glycated hemoglobin A1c levels between 6.5 percent and 10 percent were selected for the Phase 2 randomized study. The research actually took place over a two year span from 2017 to 2019 involving trial sites in both America and the United Kingdom.
Researchers found by the end of the study that almost 21 percent decrease in body fat in the Bimagrumab group as compared to 0.5 percent in the placebo group. The results also revealed the investigational product group gained 3.6 percent of lean mass compared with a loss of 0.8 percent in the placebo group. By combining loss in body fat and gain in lean mass, the investigators calculations led to a net 6.5 reduction in body weight in patients receiving the investigational drug as compared to 0.8 percent weight loss in the subjects in the placebo group.
The authors shared that the study had some limitations including the small sample size of 75 participants. They also shared participant gender imbalance as more women were randomized to Bimagrumab and more men to the placebo as a possible study limitation. Partial results of the study were shared during ObesityWeek® in 2019. The study results were published earlier this month in JAMA Network Open.
The study authors did report nine serious adverse events in six patients which can be reviewed here. Adverse events were reported by 31 of 37 (83.8%) in the Bimagrumab group and 31 of 38 (81.6%) in the placebo group. Follow the link for more details.
Investigator Point of View
Steve Heymsfield, MD, FTOS, past president of The Obesity Society and corresponding author of this study, shared recently, “These exciting results suggest that there may be a novel mechanism for achieving weight loss with a profound loss of body fat and an increase in lean mass, along with other metabolic benefits.” Dr. Heymsfield is a professor and director of the Metabolism and Body Composition Laboratory at the Pennington Biomedical Research Center located in Baton Rouge, LA.
Trial Site Leads
Novartis Institutes for Biomedical Research (NIBR) and Pennington Biomedical Research Center were lead trial sites for this study. Other trial site locations included QPS-Miami Research Associates, Panax Clinical Research and Advent Health Research Institute in Orlando, Florida. Note, this latter site is the research institute of Advent Health, the largest not-for-profit Protestant health care provider in the United States and one of the largest non-profit health systems in America.
Based in Cambridge, MA, NIBR is considered the innovation engine for the Swiss-based Novartis. Long ago, Novartis understood the valuable potential of setting up research centers facilitating collaboration across scientific and organizational boundaries. Emphasizing new technologies associated with therapeutic possibilities and breakthroughs for patients, the company’s NIBR center involves at least 5,600 researchers and support staff dedicated to discovery.
Part Louisiana State University (LSU), Pennington Biomedical Research Center is at the forefront of medical discovery as it relates to understanding the causes of obesity, diabetes, cardiovascular disease, cancer and dementia. This trial site center conducts the full suite of research from basic and clinical to population studies. The center includes about 63 faculty and more than 18 post-doctoral fellows who comprise a network of 44 laboratories supported by lab technicians, nurses, dietitians and support personnel, as well as 13 highly specialized core service facilities. The center’s 450 employees perform research activities in the state-of-the-art facilities on the 222-acre Baton Rouge campus.
In the press release disclosure of interests, it turns out author Laura Coleman PhD, RD (NIBR Cambridge), and Ronenn Roubenoff, MD, MHS (NIBR Basel), both disclosed that they authored a patent for PAT058683 pending with Novartis. Moreover, Daniel S. Rooks, PhD (NIBR Cambridge) and Dr. Coleman disclosed that they are co-authors of a patent for the use of Bimagrumab in other indications no longer under study. Novartis did pay one of the investigators—Bret H Goodpaster, PhD, with Advent Research Health Institute.
About The Obesity Society
The Obesity Society recently released the trial results update via EurekAlert! A non-profit group consisting of leading scientists and health professionals devoted to understanding and reversing the epidemic of obesity and its adverse health, economic and societal effects.
Laura A Coleman, PhD, RD, Novartis Institutes for BioMedical Research, Cambridge, MA
Ram Miller, MD, Novartis Institutes for BioMedical Research, Basal, Switzerland
Other authors can be viewed at the source.