The FDA approved Rhythm Pharmaceutical’s Imcivree (setmelanotide) for patients with Bardet-Biedl syndrome.
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The U.S. Food and Drug Administration has approved Boston-based Rhythm Pharmaceutical’s Imcivree (setmelanotide) for patients with Bardet-Biedl syndrome (BBS), a rare genetic disease with a wide range of symptoms, including severe obesity.
Imcivree is already approved by the European Commission (EC) and Great Britain’s Medicines & Healthcare Products Regulatory Agency (MHRA) for obesity and control of hunger linked with genetically confirmed loss-of-function biallelic proopiomelanocortin (POMC), including PCSK1, deficiency or biallelic LEPR deficiency in adults and children six years of age and older. The drug is a melanocortin-4 receptor (MC4R) agonist. MC4R plays a key role in the biological pathway that regulates hunger, caloric intake and energy expenditure.
“This FDA approval represents a significant milestone for Rhythm, validating our strategy of developing Imcivree for people with hyperphagia and severe obesity caused by rare MC4R-pathway diseases and allowing us to provide our precision therapy to an established community of patients living with BBS and their families who are eagerly awaiting a new treatment option,” Dr. David Meeker, M.D., chair, president and chief executive officer of Rhythm, said in a statement.
“Leveraging the robust infrastructure we put in place following the initial approval of Imcivree for obesity due to biallelic POMC, PCSK1 or LEPR deficiency and our new high-touch patient support services to assist patients throughout the journey from diagnosis to ongoing treatment, we are able to make Imcivree available for BBS immediately,” he added.
On Monday, the company presented data from its long-term extension study of the drug in BBS syndrome, or POMC or LEPR deficiency obesity receiving the therapy between 18 months and three years. The presentation took place at the Endocrine Society Annual Meeting & Expo (ENDO) held in Atlanta. Forty-two patients with BBS treated with setmelanotide in Phase II or Phase III continued into the long-term extension. As of the data cutoff, 30 and 19 patients received at least 18 and 24 months of the drug, respectively. The mean percent change in body mass index (BMI) across all patients was -9.5% and -14.3% at 18 and 24 months, respectively.
BBS affects about 1,500 to 2,500 people in the U.S. They may experience insatiable hunger (hyperphagia), with severe obesity starting early in life. Other symptoms include retinal degeneration, decreased kidney function, extra fingers or toes (polydactyly), hypogonadism and learning disabilities.
The approval was based on data from the company’s pivotal Phase III trial. The drug demonstrated early, significant and sustained weight reduction, hitting its primary endpoint and all key secondary endpoints. The mean percentage change in BMI was -7.9% without diet and exercise. There was a statistically significant mean change in hunger score of -2.1 at 52 weeks in patients 12 years of age and older who could self-report their hunger.
Dropped toward the end of the announcement, the company indicated the FDA had issued a complete response letter (CRL) for the sNDA for setmelanotide in Alström syndrome.
Alström syndrome is also a rare disease affecting a broad range of body systems. It is marked by a progressive loss of vision and hearing, a type of heart disease that enlarges and weakens the heart muscle called dilated cardiomyopathy, obesity, type 2 diabetes and short stature. It ranges greatly in severity. It is caused by mutations in the ALMS1 gene.
Meeker said, “We appreciate the FDA’s careful review of our sNDA for Imcivree for the treatment of Alström syndrome but are disappointed in this outcome. We are tremendously grateful to the Alström syndrome patients, caregivers and physicians who participated in our clinical development efforts and look forward to providing an update regarding our path forward.”
The company also announced it had entered into a Revenue Interest Financing Agreement with HealthCare Royalty Partners for an investment of up to $100 million. Rhythm plans to use the proceeds and its cash on hand to support worldwide commercialization activities for Imcivree and ongoing clinical programs. Under the deal, it will receive an initial investment of $37.5 million due to Thursday’s approval.
