Rhythm Pharmaceuticals, Inc. (Nasdaq: RYTM) is delighted to announce that the French National Agency for Medicines and Health Products Safety (ANSM) and French National Authority for Health (HAS) have granted pre-marketing early access authorization, also known as AP1 (Autorisation d’Accès Précoce). IMCIVREE® (setmelanotide), their MC4R agonist, is available for patients with lesional hypothalamic obesity. This groundbreaking decision will help to transform the lives of patients and their families living with hyperphagia and severe obesity caused by rare melanocortin-4 receptor (MC4R) pathway diseases.
The French National Agency for Medicines and Health Products (ANSM), in coordination with Health Authority (HAS), recently gave setmelanotide, an innovative therapy developed by Rhythm, early access in France before European regulatory approval. This was possible due to the Positive Benefit/Risk Ratio recognized by the ANSM and HAS, as well as the fact that no other therapeutic alternatives were available. Patients participating in this Access With Prior Authorization 1 (AP1) program are fully covered and Rhythm will be reimbursed for any treatments.
Melanotide, a revolutionary treatment for Bardet-Biedl Syndrome (BBS), has been available to French patients since July 2022 through an innovative program. This newfound access to this advanced form of medical aid is helping to improve the daily lives of those affected by the debilitating disorder.
Today, we are thrilled and honoured to announce a major milestone in our mission to provide global access to setmelanotide for patients with hypothalamic obesity. Setmelanotide has been granted the unique AP1 status by the French regulatory authorities, recognizing the severity of this unmet medical need. We are committed to working with French experts to make sure patients can access this life-saving treatment.
Hypothalamic obesity is an incredibly rare acquired form of extreme obesity that arises when the neural pathways in the hypothalamic region of the brain are damaged. These pathways, known as the MC4R pathway, have the critical responsibility of managing hunger and weight. This type of obesity is chiefly seen to follow the growth and surgical removal of craniopharyngioma, astrocytoma or other rare brain tumors.
After such a traumatic event, patients typically observe accelerated weight gain, an abrupt decrease in energy expenditure and a newfound sense of hunger. In France, around 500 to 2,000 people live with hypothalamic obesity, with an estimate of 50 to 200 new cases reported each year. The prevalence of this disorder in the United States is estimated to belong in the range of 5,000 to 10,000 people annually, with about 500 new patients addressing its burden.
Rhythm’s Phase 3 trial for the treatment of hypothalamic obesity is underway, as results from the Phase 2 trial illustrated promising progress in weight loss for those with hypothalamic obesity. Of the 18 patients enrolled in Phase 2, 16 (89%) achieved a BMI reduction of at least 5% after 16 weeks of setmelanotide treatment. On average, patients experienced a 14.5% decrease in BMI at Week 16 from the start of the trial.
Patients suffering from hypothalamic obesity are left without any effective or approved therapeutic options – traditional lifestyle changes have been proven to be insufficient in controlling their weight and appetite. Professor Christine Poitou, Professor of Nutrition at the Pitié-Salpêtrière University Hospital in Paris, is determined to address this significant unmet need for patients with severe obesity and hyperphagia with the first approved therapy. This is a major breakthrough for people with hypothalamic obesity.
About Rhythm Pharmaceuticals
Rhythm is a biopharmaceutical company dedicated to transforming the lives of those living with rare melanocortin-4 receptor (MC4R) caused diseases like severe obesity and hyperphagia. Our leading asset, IMCIVREE (setmelanotide) has been approved by the U.S. FDA, the European Commission, and the UK’s MHRA, and is ready for use in accordance with product labeling.
Furthering our commitment to improving rare MC4R pathway diseases, Rhythm is currently engaged in a broad clinical development program for setmelanotide and a suite of preclinical investigational candidates designed to treat congenital hyperinsulinism. We are proud to be headquartered in Boston, MA and are excited to be leading the charge on these transformative treatments.
Setmelanotide Indication
Setmelanotide, now approved by the FDA in the United States, is a revolutionary treatment option for adults and children aged 6 and above with genetic or syndromic obesity resulting from mutations in genes such as POMC, PCSK1, or LEPR. Test results that detect pathogenic, likely pathogenic, or uncertain significance (VUS) or BBS variants in these genes can help identify the right candidates for setmelanotide and help them achieve sustainable weight management.
For adults and children 6 and over, Setmelanotide has been approved in the European Union for the management of obesity and the alleviation of hunger associated with confirmed Bardet-Biedl Syndrome (BBS), as well as confirmed two-gene disruptions in Proopiomelanocortin, PCSK1 or Leptin Receptor (LEPR) genes.
Setmelanotide offers hope for those with obesity caused by Bardet-Biedl Syndrome (BBS), genetically-confirmed biallelic pro-opiomelanocortin, proprotein convertase subtilisin/kexin type 1, or leptin receptor deficiency. Approved for use by Health Canada, this medication provides an answer for adults and children age six and older, allowing them to finally take control of their lives.
Limitations of Use
Setmelanotide is not indicated to treat certain medical conditions as its potential to be effective in those circumstances is simply not present. Therefore, it is imperative to ensure that you have the correct treatment before assuming setmelanotide will be effective.
- Are you struggling with obesity and suspect that it may be caused by a deficiency in POMC, PCSK1 or LEPR? Variants of these genes that are classified as ‘benign’ or ‘likely benign’ could be to blame.
- Other forms of obesity not linked to POMC, PCSK1 or LEPR deficiency, or BBS are also prevalent, including obesity related to other genetic syndromes, as well as the increasingly commonplace polygenic obesity.
In Europe, Setmelanotide should be carefully prescribed and monitored by qualified specialists with substantial experience in treating obesity with underlying genetic origins.
WARNINGS AND PRECAUTIONS
Setmelanotide can cause your skin to darken and produce more pigment. That’s why we recommend that you get a full body skin examination every year to keep an eye on any existing and new pigmentary lesions before and while using setmelanotide. Keeping an eye on your skin is an important part of your health routine!
Heart health is an essential part of overall wellness, and as part of routine medical care, monitoring heart rate and blood pressure is especially important for patients being treated with setmelanotide. At least every six months, healthcare providers should check these vital signs in order to ensure that the patient’s health is maintained.
Setmelanotide has been found to cause unexpected penile erections in some clinical trials. If men experience an erection for more than four hours, they should seek medical help immediately to prevent the dangerous condition of priapism.
Depression can be an unfortunate side effect of setmelanotide treatment. That’s why at every medical visit during your setmelanotide treatment, your physician will be monitoring for signs of depression. If any thoughts of suicide arise, it’s important to address them with your doctor right away. Treatment with setmelanotide may have to be discontinued if a patient’s depression continues to worsen.
Prescribing physicians should monitor their pediatric patients’ response to setmelanotide therapy. It is important to assess the impact of weight loss on their growth and maturation, for which height and weight should be monitored in comparison to age- and sex-appropriate growth curves. Keeping a close eye on this progress will help ensure the best care for growing children.
This medicinal product contains 10 mg of benzyl alcohol in each ml, posing potential risks to pregnant or breastfeeding patients. Metabolic acidosis caused by the accumulation of benzyl alcohol over time is a major concern in individuals with hepatic or renal impairment. It is important to exercise caution when using this product to ensure the safety of these patients.
This health supplement has less than 1 mmol of sodium (equivalent to 23 mg) per dose, meaning essentially “sodium-free.” A great choice for those looking to reduce their salt consumption and manage their health!
ADVERSE REACTIONS
The most common side effects of this medication are hyperpigmentation (51%), injection site reaction (39%), nausea (33%), and headache (26%). In some cases, patients may experience discolored skin, tenderness at the injection site, queasiness, and a throbbing ache in their heads.
USE IN SPECIFIC POPULATIONS
Pregnancy
Pregnant women have not used setmelanotide, but animal studies do not suggest any significant direct reproductive harm. However, when given to pregnant rabbits, setmelanotide caused reduced food consumption in mothers, leading to possible embryo-fetal effects. Out of caution, women who are pregnant or trying to become pregnant should not take the medication, as weight loss during pregnancy can be detrimental to the fetus.
If a woman gets pregnant while already taking setmelanotide and has reached a stable weight, the drug can be maintained. However, pregnant women who are still losing weight should either reduce their dose or completely stop taking setmelanotide, while being monitored for the recommended weight gain during pregnancy. Everyone taking this medication should have their weight closely monitored throughout pregnancy.
Breast-feeding
Setmelanotide has been found to be excreted in the milk of nursing rats, but its presence in human milk remains unknown. Although a nonclinical study has not detected quantifiable setmelanotide concentrations in the plasma of nursing pups, it is impossible to entirely rule out the risk of exposure for newborn and infant children.
Thus, when considering the various benefits of both breastfeeding for the child and setmelanotide therapy for the mother, the ultimate decision should be made between discontinuing breastfeeding or discontinuing/abstaining from setmelanotide therapy.
Fertility
No adverse effects on fertility have been noted in animal studies of setmelanotide, although no data is available regarding its effects in humans. To ensure the safety of individuals, European national reporting systems have been established to record and respond to any adverse reactions to the drug.
Forward-looking Statements
Rhythm Pharmaceuticals, Inc. is pleased to announce its forward-looking statements regarding setmelanotide, its potential, safety, efficacy, and progression, potential regulatory submissions, approvals and timing, and overall business strategy and plans. This includes the planned commercialization of IMCIVREE in France, the United States, and other international regions.
These plans are subject to numerous risks and uncertainties that should be taken into consideration, including our liquidity and expenses, clinical trials, regulatory approvals, data analysis and reporting, product liability lawsuits, and third-party reimbursement practices.
No guarantees have been made about the success of these plans and any related assurances should be taken with caution. Regardless, Rhythm Pharmaceuticals is excited to bring these potential treatments to its consumers and hopes that their plans can help improve the lives of many people.