NICE Recommends Rhythm’s ▼IMCIVREE® (setmelanotide) for Treating Obesity and Controlling Hunger Caused by POMC or LEPR Deficiency
- IMCIVREE will be funded and available for use within 90 days in the National Health Service -
POMC and LEPR deficiencies are caused by genetic variants that disrupt signaling of the MC4R pathway, a system in the hypothalamus that regulates hunger, satiety and energy expenditure. Disrupted MC4R signaling causes hyperphagia and early-onset, severe obesity. People living with obesity due to POMC or LEPR deficiency struggle with insatiable hunger, also known as hyperphagia, and extreme obesity beginning at a young age.1,2 These diseases severely affect the quality of life of people living with them, as well as that of their families and caregivers, with many reporting a significant psychological burden, which can manifest as poor mental health, low self-esteem or depression. NICE concluded that obesity caused by POMC or LEPR deficiency is a debilitating condition associated with multiple comorbidities.
“The effects of rare MC4R pathway diseases, including POMC and LEPR deficiency, go far beyond a patients’ weight and hunger, severely affecting their ability to maintain a normal quality of life beginning in childhood,” said
The final NICE recommendation is aligned to the European Marketing Authorization (EMA) and
“We are delighted by this positive NICE recommendation, which makes available the first therapeutic option for patients with POMC or LEPR deficiency in
The full text of the NICE recommendation can be found at: https://www.nice.org.uk/guidance/hst21/chapter/1-Recommendations.
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
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 POMC, PCSK1 or 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) or Bardet-Biedl syndrome (BBS).
Limitations of Use
IMCIVREE should be prescribed and supervised by a physician with expertise in obesity with underlying genetic etiology.
WARNINGS AND PRECAUTIONS
Skin Monitoring: Setmelanotide may lead to generalised increased skin pigmentation and darkening of pre-existing naevi because of its pharmacologic effect. Full body skin examinations should be conducted annually to monitor pre-existing and new skin pigmentary lesions before and during treatment with setmelanotide.
Heart rate and blood pressure monitoring: Heart rate and blood pressure should be monitored as part of standard clinical practice at each medical visit (at least every 6 months) for patients treated with setmelanotide.
Prolonged penile erection: Spontaneous penile erections have been reported in clinical trials with setmelanotide. Patients who have a penile erection lasting longer than 4 hours should be instructed to seek emergency medical attention for potential treatment of priapism.
Depression: In clinical trials, depression has been reported in patients treated with setmelanotide. Patients with depression should be monitored at each medical visit during treatment with IMCIVREE. Consideration should be given to discontinuing IMCIVREE if patients experience suicidal thoughts or behaviours.
Paediatric Population: The prescribing physician should periodically assess response to setmelanotide therapy. In growing children, the impact of weight loss on growth and maturation should be evaluated. The prescribing physician should monitor growth (height and weight) using age- and sex-appropriate growth curves.
Excipients: This medicinal product contains 10 mg benzyl alcohol in each ml. Benzyl alcohol may cause allergic reactions. Patients who are pregnant or breastfeeding should be advised of the potential risk from the excipient benzyl alcohol, which might accumulate over time and cause metabolic acidosis. This medicinal product should be used with caution in patients with hepatic or renal impairment, because of the potential risk from the excipient benzyl alcohol which might accumulate over time and cause metabolic acidosis.
The most frequent adverse reactions are hyperpigmentation (51%), injection site reaction (39%), nausea (33%), and headache (26%).
USE IN SPECIFIC POPULATIONS
There are no data from the use of setmelanotide in pregnant women. Animal studies do not indicate direct harmful effects with respect to reproductive toxicity. However, administration of setmelanotide to pregnant rabbits resulted in decreased maternal food consumption leading to embryo-foetal effects. As a precautionary measure, IMCIVREE should not be started during pregnancy or while attempting to get pregnant as weight loss during pregnancy may result in fetal harm. If a patient who is taking setmelanotide has reached a stable weight and becomes pregnant, consideration should be given to maintaining setmelanotide treatment as there was no proof of teratogenicity in the nonclinical data. If a patient who is taking setmelanotide and still losing weight gets pregnant, setmelanotide should either be discontinued, or the dose reduced while monitoring for the recommended weight gain during pregnancy. The treating physician should carefully monitor weight during pregnancy in a patient taking setmelanotide.
It is unknown whether setmelanotide is excreted in human milk. A nonclinical study showed that setmelanotide is excreted in the milk of nursing rats. No quantifiable setmelanotide concentrations were detected in plasma from nursing pups. A risk to the newborn/infant cannot be excluded. A decision must be made whether to discontinue breastfeeding or to discontinue/abstain from IMCIVREE therapy taking into account the benefit of breastfeeding for the child and the benefit of therapy for the mother.
No human data on the effect of setmelanotide on fertility are available. Animal studies did not indicate harmful effects with respect to fertility
To report SUSPECTED ADVERSE REACTIONS, contact Rhythm Pharmaceuticals at +1 (833) 789-6337.
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, and our expectations surrounding potential regulatory submissions, approvals and timing thereof, and our business strategy and plans, including regarding commercialization of IMCIVREE in the United Kingdom, the United States and other international regions, including expectations surrounding funding and availability of IMCIVREE in the National Health Service and related timing. 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, the ability to obtain or maintain coverage and adequate reimbursement for IMCIVREE or our other product candidates, risks associated with data analysis and reporting, 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 quarter 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
+44 020 8106 7891
1 Ayers KL, Glicksberg BS, Garfield AS, et al. Melanocortin 4 receptor pathway dysfunction in obesity: patient stratification aimed at MC4R agonist treatment. J Clin Endocrinol Metab. 2018;103(7):2601-2612.
2 Krude H, Biebermann H, Luck W, Horn R, Brabant G, Grüters A. Severe early-onset obesity, adrenal insufficiency and red hair pigmentation caused by POMC variants in humans.
Source: Rhythm Pharmaceuticals, Inc.