Rhythm Pharmaceuticals Announces Positive Interim Results from Phase 2 Clinical Trial Evaluating Setmelanotide in Hypothalamic Obesity
--All evaluable patients (N=11) achieved BMI decrease of more than 5 percent at 16 weeks on setmelanotide therapy--
--17.2 percent mean reduction in BMI at 16 weeks--
--15.8 percent (15.9 kg or 35.1 lb) mean weight reduction achieved at 16 weeks--
--Mean change in hunger score of -2.7--
--Management to host conference call at
“Therapeutic options are very limited for patients with hypothalamic obesity, which is the result of damage to the medial hypothalamic region of the brain where MC4R pathway signaling is impaired due to certain tumors and their treatment. Surgical intervention, radiation treatment or even the growth and position of the tumor itself can leave patients with aggressive, rapid and debilitating weight gain,” said
As of the data cutoff date of
- -17.2 percent mean percentage change in BMI (range: -37.2 percent, -6.7 percent);
- -15.8 percent mean change (range: -34.9 percent, -6.7 percent) in body weight from baseline weight of 107.1 kg (range, 39.0 kg, 141.4 kg) or 236.1 lb;
- -15.9 kg (range, -28.2 kg, -6.7 kg) or -35.1 lb mean weight loss from baseline.
Data highlights from an interim analysis of completers (n=9) include:
- -19.5 mean percent change in BMI (range: -37.2 percent, -10 percent);
- -17.8 mean percent change (range: -34.9 percent, -10.7 percent) in body weight from baseline weight of 107.8 kg (range: 39.0 kg, 141.4 kg) or 236.1 lb;
- -17.8 kg (range: -28.2 kg, -9.5 kg) or -37.7 lb mean weight loss from baseline.
Setmelanotide also achieved a meaningful reduction in hunger scores. The mean change in hunger score for patients older than 12 years old who completed 16 weeks on therapy (n=7) was -2.7 on a scale of 1-10, with 10 being most hungry.
Consistent with prior clinical experience in other rare MC4R pathway diseases, setmelanotide was observed to be generally well tolerated. The most frequently reported treatment-emergent adverse events included nausea, vomiting, COVID-19, diarrhea, injection site reaction and abdominal pain.
“We are highly encouraged by these initial results, which reinforce the importance of the MC4R pathway in regulating hunger, caloric intake, energy expenditure and ultimately body weight, as well as the potential role of setmelanotide in the management of diseases where this pathway is impaired,” said
About the Phase 2 Clinical Trial in Hypothalamic Obesity
The Phase 2 clinical trial is a multi-center, open-label, proof-of-concept study that enrolled 18 patients with hypothalamic obesity who are between 6 and 28 years old. The trial consisted of 16 weeks of treatment with setmelanotide administered once daily by subcutaneous injection, including an initial period of dose titration. The primary endpoint is the percentage of patients who achieve more than 5 percent reduction in BMI from baseline after 16 weeks of treatment compared to a historic control of less than 5 percent in this population.
Of the 18 patients enrolled in this Phase 2 study, three discontinued due to adverse events, each of whom had achieved a reduction in BMI of more than 5 percent at the time they discontinued, and one patient was discontinued due to documented non-compliance to therapy. In total, 14 of 18 patients enrolled in this study remained on setmelanotide therapy as of
About Hypothalamic Obesity
Hypothalamic obesity is a rare, acquired form of extreme obesity that occurs following damage to the hypothalamic region of the brain, which is responsible for controlling physiological functions such as hunger and weight regulation. It most frequently follows the growth or surgical removal of craniopharyngioma, astrocytoma or other rare brain tumors. Patients experience rapid weight gain, a reduction in energy expenditure an increase in hunger in the first six to 12 months following tumor resection, and ultimately develop severe obesity. In addition, people living with hypothalamic obesity may also experience delayed puberty and infertility, decreased physical activity, excessive daytime sleepiness, attention hyperactivity disorder, seizures and psychiatric conditions. Based on an analysis of incidence rates and prevalence reports of certain brain tumor types, as well as survival and obesity rates tied to these brain tumor types, Rhythm estimates there are approximately 5,000-10,000 patients living with hypothalamic obesity in
Conference Call Information
Rhythm will host a live conference call and webcast at
A live webcast of the call will also be available under "Events and Presentations" in the Investor Relations section of the Company’s website at http://ir.rhythmtx.com/. The archived webcast will be available on Rhythm’s website approximately two hours after the conference call and will be available for 30 days following the call.
About Rhythm Pharmaceuticals
Rhythm is a commercial-stage biopharmaceutical company committed to transforming the lives of patients and their families living with hyperphagia and severe obesity caused by rare melanocortin-4 receptor (MC4R) pathway diseases. Rhythm’s precision medicine, IMCIVREE (setmelanotide), is approved by the
Setmelanotide is a melanocortin-4 receptor (MC4R) agonist. The MC4R is part of the key biological pathway that regulates hunger, caloric intake and energy expenditure. Variants in genes may impair the function of the MC4R pathway, potentially leading to decreased energy expenditure, hyperphagia and early-onset, severe obesity. Rhythm is developing setmelanotide as a targeted therapy to potentially restore the function of an impaired MC4R pathway and, in so doing, potentially increase energy expenditure, reduce hunger and weight in patients with rare genetic diseases of obesity.
In the EU and Great Britain, IMCIVREE is indicated for the treatment of obesity and the control of hunger associated with genetically confirmed loss-of-function biallelic POMC, including PCSK1, deficiency or biallelic LEPR deficiency in adults and children 6 years of age and above. IMCIVREE should be prescribed and supervised by a physician with expertise in obesity with underlying genetic etiology.
Rhythm’s Type II variation application to the
IMCIVREE® (setmelanotide) Indication
In the United States, IMCIVREE is indicated for chronic weight management in adult and pediatric patients 6 years of age and older with monogenic or syndromic obesity due to:
- Pro-opiomelanocortin (POMC), proprotein convertase subtilisin/kexin type 1 (PCSK1) or leptin receptor (LEPR) deficiency as determined by an FDA-approved test demonstrating variants in POMC, PCSK1 or LEPR genes that are interpreted as pathogenic, likely pathogenic, or of uncertain significance (VUS)
- Bardet-Biedl syndrome (BBS)
Limitations of Use
IMCIVREE is not indicated for the treatment of patients with the following conditions as IMCIVREE would not be expected to be effective:
- Obesity due to suspected POMC, PCSK1 or LEPR deficiency with POMC, PCSK1 or LEPR variants classified as benign or likely benign
- Other types of obesity not related to POMC, PCSK1 or LEPR deficiency, or BBS, including obesity associated with other genetic syndromes and general (polygenic) obesity
WARNINGS AND PRECAUTIONS
Disturbance in Sexual Arousal: Spontaneous penile erections in males and sexual adverse reactions in females have occurred. Inform patients that these events may occur and instruct patients who have an erection lasting longer than 4 hours to seek emergency medical attention.
Depression and Suicidal Ideation: Depression and suicidal ideation have occurred. Monitor patients for new onset or worsening depression or suicidal thoughts or behaviors. Consider discontinuing IMCIVREE if patients experience suicidal thoughts or behaviors, or clinically significant or persistent depression symptoms occur.
Skin Pigmentation and Darkening of Pre-existing
Risk of Serious Adverse Reactions Due to Benzyl Alcohol Preservative in Neonates and Low Birth Weight Infants: IMCIVREE is not approved for use in neonates or infants. Serious and fatal adverse reactions including “gasping syndrome” can occur in neonates and low birth weight infants treated with benzyl alcohol-preserved drugs.
- The most common adverse reactions (incidence ≥20%) included skin hyperpigmentation, injection site reactions, nausea, headache, diarrhea, abdominal pain, vomiting, depression, and spontaneous penile erection.
USE IN SPECIFIC POPULATIONS
Treatment with IMCIVREE is not recommended when breastfeeding. Discontinue IMCIVREE when pregnancy is recognized unless the benefits of therapy outweigh the potential risks to the fetus.
To report SUSPECTED ADVERSE REACTIONS, contact
Please see the full Prescribing Information for additional Important Safety Information.
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements contained in this press release that do not relate to matters of historical fact should be considered forward-looking statements, including without limitation statements regarding the potential, safety, efficacy, and regulatory and clinical progress of setmelanotide, including with respect to the Phase 2 clinical trial evaluating setmelanotide in hypothalamic obesity and the Phase 3 development strategy, our expectations surrounding potential regulatory submissions, approvals and timing thereof, and our business strategy and plans, including regarding commercialization of IMCIVREE. 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 that interim, “topline” and preliminary data from our clinical trials that we announce or publish from time to time may change as more patient data become available and are subject to audit and verification procedures that could result in material changes in the final data risks associated with data analysis and reporting, our ability to successfully commercialize setmelanotide, our liquidity and expenses, the impact of the COVID-19 pandemic on our business and operations, including our preclinical studies, clinical trials and commercialization prospects, and general economic conditions, and the other important factors discussed under the caption “Risk Factors” in our Quarterly Report on Form 10-Q for the quarterly period ended March 31, 2022 and our other filings with the Securities and Exchange Commission. Except as required by law, we undertake no obligations to make any revisions to the forward-looking statements contained in this release or to update them to reflect events or circumstances occurring after the date of this release, whether as a result of new information, future developments or otherwise.
Head of Investor Relations and Corporate Communications
Stern Investor Relations, Inc.
Berry & Company Public Relations
Source: Rhythm Pharmaceuticals, Inc.