New Data on Setmelanotide for Bardet-Biedl Syndrome

Long-term extension (LTE) data is now available for setmelanotide, which is a treatment for rare causes of obesity, such as Bardet-Biedl syndrome (BBS) and POMC or LEPR deficiency. Data on all of these is being shared at the Endocrine Society Annual Meeting & Expo (ENDO) from June 11th until the 14th. You can learn more about this Atlanta-based event here.

New Data on Setmelanotide

Rhythm Pharmaceuticals developed this drug for rare and genetic forms of obesity. They’ve been studying setmelanotide for a while, and now have data that shows reductions in body mass index (BMI) and weight continue for up to three years.

Data for BBS Patients

42 patients with BBS from the phase 2 and 3 trials of this therapy were enrolled in the LTE study, 30 of whom were treated for at least 18 months, and 19 of which were treated for a minimum of 24 months. Data from this long-term study includes:

  • Those over the age of 18 achieved a weight change of -8.6% after 18 months
    • The weight change was -14.9% after 24 months
  • Out of 15 patients, six reached a weight reduction of more than or equal to 10% after 18 months
    • Five of these six then went on to hold this statistic after 24 months
  • The average change in BMI across all ages was -9.5% after 18 months, and -14.3% after 24 months
  • Patients under the age of 18 achieved an average change in BMI Z score of -0.83 after 18 months and -0.72 after 24 months
    • Every participant under age 18 saw a reduction in BMI Z score of ≥0.2 points
      • 12 of these 13 participants experienced a reduction of ≥0.3 points after 18 months of treatment
        • Nine of these 12 went on to see the same reduction after 24 months

At the time that the data were cut off, 38 patients were continuing with setmelanotide therapy, whereas four had discontinued.

You can find more data in the poster presentation, which is titled “Long-term Efficacy of Setmelanotide in Patients with Bardet-Biedl Syndrome.”

Data for POMC and LEPR Deficiency Patients

24 participants sourced from the phase 2 and 3 trials, 21 of whom received at least 24 months’ worth of treatment, and 15 of whom completed 36 months of therapy. Data includes:

  • Throughout all participants, the average change in BMI was -16.7% after 24 months and -17.5% after 36 months
  • Those younger than age 18 saw an average BMI Z score change of −0.94 after 24 months and −0.73 after 36 months
    • Eight of the ten young patients achieved a reduction in BMI Z score of ≥0.3 points after 24 month
      • Two of four patients continuing at 36 months saw a continued reduction of at least 0.3 points
  • The average mean change in body weight for patients over the age of 18 was −16.7% after 24 months and −13.5% after 36 months
    • Seven of ten patients achieved at least a 10% reduction in weight after 24 months
      • Five of eight patients saw this same reduction after 36 months
  • No new safety concerns were seen, and the safety profile remained consistent with prior research

At the time of the cutoff of data, 24 patients were still being treated with setmelanotide. Three had discontinued.

If you want to read more about this portion of the LTE trial, you should check out the poster presentation titled, “Long-term Efficacy of Setmelanotide in Patients With POMC or LEPR Deficiency Obesity.” Additionally, all of Rhythm Pharmaceutical’s presentations can be found on their website. The source article can be found right here for more information as well.

About BBS

Bardet-Biedl syndrome, once thought to be the same as Laurence-Moon syndrome, is an autosomal recessive disorder that primarily affects cells that receive light. Cone and rod cells in the retina deteriorate when one has this syndrome. There are twelve separate genes that can cause Bardet-Biedl syndrome, but the most common one is the BBS1 gene. The similarity between these cells is that they all affect cilia, which cover nearly all cells in the body. Cilia are responsible for normal health and development. Because these genes affect the function of the cilia, nearly all of the symptoms are due to this dysfunction. These symptoms can vary greatly from person to person, but they are characterized by visual impairments. People’s vision worsens as they age, and they can experience tunnel vision, night-blindness, or complete blindness. Along with the worsening of vision, people can experience crossed eyes, rapid eye movement, cataracts, or glaucoma.

Beyond visual impairments, symptoms can include an additional toe or finger, obesity, short digits, webbing of the fingers or toes, short, wide, or flat feet, delayed puberty, speech impediments, behavioral issues, abnormalities in gait, high blood pressure, trouble with smelling, and ataxia. After these symptoms are noticed by a doctor, a clinical examination or genetic testing can diagnose Bardet-Biedl syndrome. No cure for this syndrome currently exists, but there are treatments that can help to treat symptoms. Surgery can help to correct webbing of the fingers or toes and extra digits, and lifestyle changes can help to manage obesity. For other symptoms, healthcare professionals recommend finding a specialist to monitor and manage them.

About POMC and LEPR Deficiency

Let’s start with proopiomelanocortin (POMC) deficiency. As the name suggests, a mutated POMC gene causes this condition, and it is inherited in an autosomal recessive pattern. This genetic alteration causes obesity caused by insatiable hunger, pale skin, and adrenal insufficiency, which causes cholestasis, low blood sugar, and seizures. Unfortunately, there are no treatments specifically for POMC deficiency (at the time of this article), so doctors focus on the patient’s specific symptoms.

Turning to LEPR deficiency, this rare genetic disorder is very similar to POMC deficiency. The main difference is its genetic cause – a mutated LEPR gene. This gene is needed to produce the leptin receptor protein. When this protein is mutated, it cannot correctly receive the hormone leptin, which is responsible for telling our brain that we’re full. So when the receptor is not working properly, affected individuals never receive the “I’m full” message, leading to the main characteristic of this disease: insatiable hunger causing obesity. Another symptom is a delay in the onset of puberty.

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