In a recent press release, biopharmaceutical company Rhythm Pharmaceuticals (“Rhythm”) announced positive data from a Phase 3 clinical trial. During the trial, Rhythm evaluated setmelanotide for patients with Bardet-Biedl syndrome (BBS) and/or Alstrom syndrome. Although the trial met its secondary endpoints for patients with Alstrom syndrome and BBS, none of the patients with Alstrom syndrome ultimately achieved primary endpoints on their own.
Setmelanotide
Within the clinical trial, researchers evaluated setmelanotide (IMCIVREE), a MC4R agonist. Typically, Alstrom syndrome and BBS cause insatiable hunger. Normally, the MC4 receptor (MC4R) plays a role in the bodily pathway that regulates energy, caloric intake, and hunger. Thus, setmelanotide is designed to lower hunger and promote weight loss. The drug is currently approved for patients with genetic-related obesity caused by POMC, PCSK1, or LEPR deficiency. Additionally, setmelanotide received Breakthrough Therapy and Priority Medicines designations.
38 patients enrolled in the clinical trial. Of these, 6 had Alstrom syndrome and 32 had Bardet-Biedl syndrome. Over a 52-week period, patients first received either a placebo or setmelanotide for 14-weeks. Following the initial 14 weeks, all patients received setmelanotide. Key findings include:
- No patients with Alstrom syndrome lost at least 10% of their body weight. However, 11 patients with BBS achieved this endpoint.
- 60.2% of participants saw at least a 25% reduction in hunger.
- The mean body weight loss was -6.2% and the mean hunger loss was -30.8%.
- Setmelanotide was generally well-tolerated. Side effects included nausea, vomiting, and injection site reactions.
Alstrom Syndrome
Mutated ALMS1 genes cause Alstrom syndrome, a rare genetic disorder. Because the mutation is inherited in an autosomal recessive pattern, someone must receive one defective copy from each parent in order to inherit this condition. Symptoms vary in severity, even within members of the same family. Additionally, symptoms appear in infancy for some, and in adolescence or adulthood for others. Symptoms include:
- Hearing and vision loss
- Type 2 diabetes
- Enlarged heart
- Changes in organ function
- Short stature
- Obesity
- Acanthosis nigricans, or the darkening and thickening of skin in body folds
Learn more about Alstrom syndrome.
Bardet-Biedl Syndrome (BBS)
In most cases, Bardet-Biedl syndrome (BBS) is caused by a BBS1 gene mutation. However, 12 different genes have been linked to this rare disorder. BBS impacts many body systems. Primarily, it impacts cilia function, where cilia usually play a role in health and development. Symptoms vary in appearance and severity, but include:
- Impaired coordination
- Learning difficulties
- Obesity
- Progressive vision loss
- Rapid eye movements
- Cataracts
- Extra fingers or toes
- Glaucoma
- Webbed fingers and toes
- Short, wide, and flat feet
- Delayed puberty
- Anxiety and depression
- High blood pressure
