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|Rhythm Pharmaceuticals Announces Promising Clinical Data in MC4R Pathway Heterozygous Obesity and Strategy for Further Development|
-- Stratifying Enrollment of MC4R Pathway Heterozygous (HET) Patients in Phase 2 Basket Study Based on Loss-of-Function (LOF) Variants --
-- Preliminary Data Show Consistent Weight Loss and Decreases in Hunger Observed in Patients with High-Impact LOF Variants --
-- Management to Host Conference Call at
“We are committed to advancing setmelanotide as swiftly as possible, with the goal of addressing the severe, early-onset obesity and relentless hunger experienced by people living with rare genetic disorders of obesity,” said
HET obesity is caused by the mutation of one of two genetic copies of a gene in the MC4R pathway and can include patients with heterozygous mutations in genes such as POMC, PCSK1 and LEPR. While there are numerous individual case histories of HET patients with severe, early-onset obesity and hyperphagia, HET patients have variable penetrance of obesity. Variable penetrance of disease in patients with heterozygous variants is a phenomenon observed in many genetic disease states. In patients with HET obesity, Rhythm believes this variability may be driven by the type of LOF variant, with higher-impact LOF variants more substantially impairing MC4R pathway function and, therefore, increasing the likelihood of developing hyperphagia and, subsequently, severe obesity.
Rhythm’s clinical development efforts are initially focused on achieving proof-of-concept in patients with well-characterized, high-impact LOF variants. Patients with these variants can present clinically with the same severe, early-onset obesity and hyperphagia characteristic of other rare genetic disorders of obesity. Rhythm estimates a prevalence of upwards of 20,000 severely obese people living with high-impact LOF variants in
New Clinical Data from Phase 2 Basket Study in HET Obesity
Today, Rhythm announced preliminary data from 13 HET patients who were treated with setmelanotide, including four patients with high-impact LOF variants and nine patients with other LOF variants:
Consistent with prior clinical experience, setmelanotide continues to be well-tolerated. There were no serious AEs reported and no new discontinuations due to AEs since those reported in
Clinical Development Plans in HET Obesity
Rhythm plans to continue enrolling HET patients in its Phase 2 basket study in cohorts stratified by LOF variant. In addition to pursuing proof-of-concept in high-impact LOF variants, Rhythm also plans to explore setmelanotide’s potential in additional patient cohorts, including patients with partial LOF or newly-characterized variants, patients with more common variants, and patients with composite HET variants. Rhythm expects patient enrollment to continue at least through the remainder of 2019, with updated data to follow in 2020. Rhythm anticipates that these data will help inform the most appropriate strategy to support the potential registration and approval of setmelanotide for the treatment of setmelanotide-responsive subgroups of HET obesity.
In parallel, Rhythm intends to further ongoing efforts to better understand HET obesity and facilitate patient identification. In order to add to the pool of high-impact variants, Rhythm is undertaking a comprehensive effort to screen and classify new and uncharacterized variants in the MC4R pathway, using both computational models for assessing variants and biochemical analysis of variants in POMC, PCSK1, and LEPR to assess functional impact. Rhythm estimates that there are thousands of potential new and uncharacterized HET variants in MC4R pathway genes. Additionally, the company plans to leverage the Rhythm Engine, a portfolio of programs including the GO-ID genotyping study, the TEMPO Registry and the Phase 2 basket study, to identify patients who may be eligible for treatment with setmelanotide, rapidly enroll eligible patients in the ongoing trial, and better characterize the ongoing impact and burden of disease on patients and their caregivers.
Upcoming Milestones Across Broader Setmelanotide Development Program
Rhythm is advancing its development program for setmelanotide toward key 2019 and 2020 milestones. The company expects to:
Conference Call Information
Setmelanotide is a potent, first-in-class, MC4R agonist in development for the treatment of rare genetic disorders of obesity. Setmelanotide activates MC4R, part of the key biological pathway that independently regulates energy expenditure and appetite. Variants in genes within the MC4R pathway are associated with unrelenting hunger and severe, early-onset obesity. Rhythm is currently developing setmelanotide as a replacement therapy for patients with monogenic defects upstream of MC4R, for whom there are no effective or approved therapies. The FDA has granted Breakthrough Therapy designation to setmelanotide for the treatment of obesity associated with genetic defects upstream of the MC4 receptor in the leptin-melanocortin pathway, which includes POMC deficiency obesity, LEPR deficiency obesity, BBS and Alström syndrome. The European Medicines Agency has also granted PRIority MEdicines (PRIME) designation for setmelanotide for the treatment of obesity and the control of hunger associated with deficiency disorders of the MC4R pathway.
Rhythm is a biopharmaceutical company focused on the development and commercialization of therapies for the treatment of rare genetic disorders of obesity. Rhythm is currently evaluating the efficacy and safety of setmelanotide, the company’s first-in-class MC4R agonist, in Phase 3 studies in patients with POMC deficiency obesity, LEPR deficiency obesity, BBS, and Alström syndrome. Rhythm is dedicated to improving the understanding of severe obesity that results from specific genetic disorders. For healthcare professionals, visit www.UNcommonObesity.com for more information. For patients and caregivers, visit www.LEADforRareObesity.com for more information. The company is based in Boston, MA.
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 expectations regarding its estimates of patient population, its efforts to identify patients, anticipated timing for enrollment and design of clinical trials, anticipated timing for submission of New Drug Application filings, and timing of the release of results of clinical trials. Statements using word such as "expect", "anticipate", "believe", "may", "will", "plans" 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 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
1 A genetic variant is a difference in DNA sequences between an individual and the population.
2 Total treatment duration as reported always includes any titration period, which can last 6-12 weeks before reaching a therapeutic dose.