New Trial Data Available on Setmelanotide for Bardet-Biedl Syndrome

The 59th Annual European Society for Paediatric Endocrinology (ESPE) Meeting is taking place virtually from September 22-26, 2021. During the Meeting, researchers are discussing best practices and treatments, as well as new research, within the field of pediatric endocrinology. According to a news release from biopharmaceutical company Rhythm Pharmaceuticals, Inc. (“Rhythm”), the company presented data from Phase 2 and 3 clinical trials evaluating setmelanotide for patients with Bardet-Biedl syndrome (BBS).


To begin, what exactly is setmelanotide? Approved under the brand name IMCIVREE, setmelanotide is described as:

a melanocortin-4 (MC4) receptor agonist developed for the treatment of obesity arising from proopiomelanocortin (POMC), proprotein convertase subtilisin/kexin type 1 (PCSK1), or leptin receptor (LEPR) deficiency. The drug has received its first approval in the USA for chronic weight management in patients 6 years and older with obesity caused by POMC, PCSK1 and LEPR deficiency and has been granted PRIority MEdicines (PRIME) designation by the European Medicines Agency for the treatment of obesity and the control of hunger associated with deficiency disorders of the MC4 receptor pathway.

The treatment helps with chronic weight management and hunger control in patients with these conditions. To learn more about how Rhythm is developing setmelanotide, and for what conditions, check out the company’s website.

Oral Presentation Findings

During the course of the meeting, Rhythm is presenting 3 oral presentations. While I will explain these in part below, you can learn more about the presentations and findings here.

In one oral presentation, researchers explored data from a Phase 3 clinical trial evaluating setmelanotide for patients with BBS. Altogether, this trial lasted 52 weeks (approximately 1 year), preceded by a 14-week double-blind treatment period. Findings include:

  • Patients who received setmelanotide showed significantly more weight loss and less hunger than patients receiving a placebo.
  • Those receiving treatment reduced their body mass index (BMI) by an average of 3.8% compared to those receiving a placebo.

In the next oral presentation, researchers evaluated data from the Phase 2 Basket clinical trial. Altogether, 30 patients enrolled. Those who enrolled had obesity caused by SRC1 gene mutations and POMC deficiencies. Findings include:

  • 9 patients lost 5%+ weight within 3 months of receiving setmelanotide treatment. Approximately 66% of these patients were adults (aged 18+), with 33% being pediatric patients (aged under 18).
  • Those who responded well to treatment lost significantly more weight than those who did not respond. However, even those who did not respond well to treatment lost a mean weight of approximately 2.3%.

Finally, the third oral presentation focused on setmelanotide safety and efficacy data in patients with 16p11.2 deletion syndrome and SH2B1 gene mutations. Altogether, 35 patients enrolled. Findings include:

  • Adult patients who responded to treatment saw a mean body weight loss of 7.2%, with pediatric patients seeing a mean BMI reduction of 0.25.
  • Approximately 36.4% of adult patients lost 5%+ weight within 3 months of treatment.

Poster Presentations on Setmelanotide

Outside of the oral presentations, Rhythm researchers also presented four separate posters.

In the first poster, Dr. Bhavik Shah, PhD, shared insights into the Phase 2 DAYBREAK clinical trial. During the trial, researchers explored setmelanotide in relation to patients with specific gene mutations. Specifically, researchers were evaluating the drug’s impact on 31 gene mutations which could affect the MC4R pathway. Dr. Cecilia Scimia, MD, PhD, also shared a poster presentation on the DAYBREAK trial, although her poster focused more on the overall trial design.

Next, Dr. Jennifer Miller, MD, shared efficacy and safety data on setmelanotide for patients with POMC or LEPR deficiencies. She found that 85.7% of patients with POMC achieved over 10% weight loss within a 52-week period, as well as 53.3% of patients with LEPR deficiency.

Finally, Dr. Ida Moeller, ScD, ScM, MMSc, discussed data from the Uncovering Rare Obesity genetic testing program. Using genetic samples sourced from 7,826 severely obese patients within the U.S., researchers discovered that 25% (1957 patients) had MC4R pathway gene mutations.

Setmelanotide Safety

Although setmelanotide was found to be relatively safe and well-tolerated, some adverse reactions or side effects did occur. These include:

  • Injection site reactions
  • Fatigue
  • Depression or suicidal ideation
  • Diarrhea
  • Headache
  • Abdominal and back pain
  • Spontaneous erections (in males)
  • Skin hyperpigmentation
  • Nausea and vomiting

Bardet-Biedl Syndrome (BBS)

One of the conditions researchers were evaluating setmelanotide for was Bardet-Biedl syndrome (BBS), a rare inherited disorder. BBS1 gene mutations are most commonly attributed to BBS. However, there are 12 distinct genes linked to BBS. In each case, the affected gene is associated with cilia, which play a role in our health. When these gene mutations occur, they prevent the cilia from acting normally, causing health issues. Because BBS is inherited in an autosomal recessive pattern, patients must receive one defective gene from each parent.

BBS is characterized by many changes throughout the body, such as truncal obesity, retinal deterioration, and even learning difficulties. Symptoms and severity vary between patients. Symptoms may include:

  • High blood pressure
  • Delayed puberty
  • Behavioral difficulties (obsessive-compulsive disorder, anxiety, depression)
  • Abnormal gait
  • Loss of smell
  • Extra finger or toe
  • Impaired coordination (ataxia)
  • Visual impairment
    • Deteriorating cones and rods, tunnel vision, rapid eye movements, crossed eyes, cataracts, glaucoma
  • Delayed speech
  • Webbed fingers or toes
  • Short, wide, and flat feet
  • Truncal obesity (obesity centered around the abdomen)
Jessica Lynn

Jessica Lynn

Jessica Lynn has an educational background in writing and marketing. She firmly believes in the power of writing in amplifying voices, and looks forward to doing so for the rare disease community.

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