Rhythm Pharmaceuticals Provides Update on Research and Development Programs
-- Four new MC4R pathway obesity indications added to Phase 2 Basket Study and enrolling patients --
-- Genetic sequencing of 13,567 individuals with severe obesity yields 11.7 percent (1,584 individuals) who have a rare genetic variant within MC4R pathway eligible for Phase 2 Basket Study --
-- Sequencing results supports ultra-rarity of POMC and LEPR deficiency obesity --
-- Sequencing results suggest U.S. prevalence estimates for four new indications of greater than 60,000 --
-- Updated data from continuing patients with Bardet-Biedl syndrome in Phase 2 Basket trial demonstrate 22.2 percent mean weight loss following approximately two years on therapy --
-- Rhythm R&D event in
During the event, the Company will provide a comprehensive overview of the four new melanocortin-4 receptor (MC4R) pathway-driven disorders that it has added to its Phase 2 Basket Study, as well as updated U.S. prevalence estimates for all of the MC4R pathway-driven rare genetic disorders of obesity for which it is currently evaluating setmelanotide. The Company also will share updated data from its Phase 2 Basket Study of setmelanotide in Bardet-Biedl syndrome (BBS) and Alström syndrome and provide details on ongoing community building and patient-finding efforts related to those two indications. Together, the presentations will highlight how the Rhythm Engine is working to discover disease-causing genetic variants and sequence patients to identify those living with MC4R pathway-driven disorders of obesity and potentially provide these patients with the first disease-modifying therapeutic option.
“In collaboration with partners, patients and health care providers, Rhythm is advancing toward our goal of changing the paradigm for rare genetic disorders of obesity,” said
Expansion of the Rhythm Basket Study into Four Additional Indications
Rhythm is expanding its Phase 2 Basket Study into four new indications: SRC1 deficiency obesity, SH2B1 deficiency obesity, MC4R deficiency obesity and Smith-Magenis syndrome obesity. The Company is evaluating setmelanotide for the treatment of severe obesity and unrelenting hunger, or hyperphagia, associated with these diseases.
- SRC1 deficiency obesity: SRC1 is a transcriptional coactivator that drives pro-opiomelanocortin (POMC) expression.
- SH2B1 deficiency obesity: SH2B1 is an adapter protein that regulates leptin receptor (LEPR) activity.
- MC4R deficiency obesity: The MC4R is the receptor for POMC ligands, and is responsible for the satiety effects of α/β-MSH. The Company plans to focus its development efforts on patients with potentially rescuable variants in the MC4R.
- Smith-Magenis syndrome (SMS) obesity: SMS is caused by dysfunction of the RAI1 gene, a transcription factor for a number of MC4R pathway genes, which affects POMC expression.
“We are taking an exciting step toward our foundational goal of translating our understanding of the MC4R pathway into treatments for people living with rare genetic disorders of obesity,” said
Genetic Sequencing Provides Updated U.S. Prevalence Estimates for Genetically-identified MC4R Pathway-driven Indications
Rhythm has been collaborating with partners to advance its own initiatives to sequence individuals living with early-onset, severe obesity to uncover more rare genetic disorders of obesity, and develop a better understanding of those disorders currently under study in its pivotal trials and Phase 2 Basket Study. As of
Rhythm’s genetic sequencing results have identified samples from 29 patients with POMC or LEPR deficiency obesity. This result supports that these conditions are ultra-rare, even among the portion of the population with severe, early-onset obesity. These results are consistent with Rhythm’s clinical epidemiology estimates of 100-500 POMC deficiency obesity and 500-2,000 LEPR deficiency obesity patients living in the U.S.
Additionally, Rhythm believes the sequencing yield in this cohort supports the Company’s prior estimates of greater than 20,000 people living with high-impact heterozygous obesity of the POMC, PCSK1 or LEPR genes in the U.S.
For the genetically-defined MC4R pathway indications that the Company has not previously included in prior clinical trials, the Company applied well-established functional and computational filtering processes to refine this yield and provide estimated U.S. prevalence1:
|Indication||Estimated U.S. Prevalence|
|SRC1 deficiency obesity||>23,000|
|SH2B1 deficiency obesity||>24,000|
|MC4R deficiency obesity||>10,000|
Syndromic conditions, such as SMS, BBS and Alström syndrome, are often clinically identified and confirmed by genetic testing. Rhythm estimates that there are greater than 2,400 people living with severe obesity and SMS in the U.S.
Update on Clinical Data from Phase 2 Basket Study in BBS and Alström Syndrome, and
Rhythm provided an update on data from its Phase 2 Basket Study of setmelanotide in patients with BBS and Alström syndrome. As previously disclosed in
In patients with Alström syndrome, the three patients on treatment at the Company’s last update in
“Rhythm is working to build a community to better understand the substantial, long-term burden of rare genetic and syndromic disorders of obesity on the lives of patients and their families. Both BBS and Alström syndrome are typically diagnosed via clinical presentation, which requires an informed healthcare-provider community, capable of recognizing and managing the care of these patients,” said
The live audio webcast of today’s R&D event can be accessed under “Events & Presentations” in the Investors & Media section of the Company’s website at www.rhythmtx.com. A replay of the webcast will be available on the Rhythm website for 30 days following the event.
Rhythm is a biopharmaceutical company focused on the development and commercialization of therapies for the treatment of rare genetic disorders of obesity. The company recently announced positive topline results from pivotal Phase 3 clinical trials of setmelanotide, its MC4R agonist, in patients with POMC deficiency obesity and LEPR deficiency obesity, and Rhythm expects to share the full data in forthcoming publications and medical meeting presentations. The company plans to complete its first rolling new drug application (NDA) submission to the
This press release contains certain statements that are forward-looking within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended, and that involve risks and uncertainties, including statements regarding Rhythm’s anticipated timing for enrollment of patients in clinical trials and submission of an NDA, its ongoing efforts related to patient identification, estimates of treatable patient populations, the timing of the release of results of clinical trials, the efficacy of setmelanotide in patients with POMC deficiency obesity, LEPR deficiency obesity, Bardet-Biedl Syndrome, Alström Syndrome, POMC heterozygous deficiency obesity, or POMC epigenetic disorders, as well as new indications that we may pursue. Statements using word such as “expect”, “anticipate”, “believe”, “may”, “will” and similar terms are also forward looking statements. Such statements are subject to numerous risks and uncertainties, including but not limited to, our ability to enroll patients in clinical trials, the design and outcome of clinical trials, the impact of competition, the ability to achieve or obtain necessary regulatory approvals, risks associated with data analysis and reporting, and expenses, and other risks as may be detailed from time to time in our Annual Reports on Form 10-K and quarterly reports on Form 10-Q and other reports we file with the
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1 SRC1 and SH2B1 deficiency obesity epidemiology estimates include patients with high-impact loss-of-function variants, screened through three computational algorithms applied for newly-observed variants. These calculations assume a U.S. population of 327 million, of which 1.7% have early-onset, severe obesity (Hales et al in Jama –
Source: Rhythm Pharmaceuticals, Inc.