Setmelanotide Receives FDA’s Orphan Drug Status for Alström Syndrome

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by Inês Martins PhD |

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Alström syndrome studied

The U.S. Food and Drug Administration (FDA) has granted orphan drug status to Rhythm Pharmaceuticalssetmelanotide for the treatment of people who have Alström syndrome, a rare genetic disorder of obesity.

Orphan drug designation is given to medicines with potential to be safe and effective treatments for rare conditions affecting no more than 200,000 people in the U.S. It is expected to provide regulatory support and financial benefits to help accelerate the clinical development of setmelanotide, and to ensure a seven-year period of marketing exclusivity if granted regulatory approval.

The recently granted status follows breakthrough therapy designation, also from the FDA, for the treatment of genetic obesity disorders associated with the MC4R pathway, which include Alström syndrome, Bardet-Biedl syndromePOMC deficiency, and LEPR deficiency.

“Individuals and families living with Alström syndrome face a high disease burden, which often adversely affects their daily lives, and yet there are currently no treatment options available to address this serious unmet need,” Murray Stewart, MD, chief medical officer at Rhythm, said in a press release.

“Orphan drug designation from the FDA reinforces the urgency of our work with setmelanotide in Alström syndrome, as we advance our pivotal Phase 3 trial to topline data expected by the end of this year or early next year,” Stewart said.

Rare genetic disorders of obesity such as Alström syndrome are typically due to genetic variants that interrupt signals in the MC4R pathway, causing insatiable hunger and severe, early-onset obesity.

Setmelanotide is an activator of MC4R signals, and was developed for patients with genetic defects that impair the MC4R pathway. By restoring MC4R signaling, the therapy has the potential to reduce hunger and help patients lose weight.

The investigational treatment is being studied in multiple clinical trials, including in a Phase 3 trial (NCT03746522) for people with moderate-to-severe obesity due to Alström syndrome and BBS.

After including 32 BBS patients and six individuals with Alström, the trial reached full enrollment in its pivotal group of participants. It will, however, continue recruitment for a supplemental group to meet patient demand. More information about contacts and study locations here.

The trial includes an initial period of 14 weeks during which patients randomly receive setmelanotide or a placebo, both given as an under-the-skin injection, followed by 38 weeks in which all participants will be given setmelanotide.

The trial’s main goal is to determine the proportion of patients who lose at least 10% of their body weight after 52 weeks of treatment.

A second 14-week period of treatment with setmelanotide will follow, after which participants may enroll in a separate extension trial to continue studying the safety and effectiveness of setmelanotide.

Two Phase 3 trials also are testing setmelanotide in people with POMC deficiency (NCT02896192) and LEPR deficiency (NCT03287960).

After both trials met their primary goals — with 80% of the participants with POMC deficiency and 45.5% of those with LEPR deficiency losing at least 10% of their weight after one year of treatment — Rhythm announced its intention to file a new drug application with the FDA seeking setmelanotide’s approval for these two rare genetic obesity disorders. The company also is planning to seek approval for these indications in the European Union.

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