Rhythm Pharmaceuticals, Inc. (Nasdaq: RYTM),
a commercial-stage biopharmaceutical company committed to
transforming the care of people living with rare genetic diseases
of obesity, today announced that the European Commission (EC) has
granted marketing authorization to IMCIVREE (setmelanotide) in the
European Union (EU) for the treatment of obesity and the control of
hunger associated with genetically confirmed loss-of-function
biallelic pro-opiomelanocortin (POMC), including proprotein
convertase subtilisin/kexin type 1 (PCSK1), deficiency or biallelic
leptin receptor (LEPR) deficiency in adults and children 6 years of
age and above.
“Rhythm’s Phase 3 trials confirmed that treatment with IMCIVREE
may deliver clinically meaningful impacts on obesity and severe
hunger or hyperphagia. Many patients enrolled in these studies
experienced weight loss of a magnitude that is unprecedented in the
natural history of rare genetic diseases of obesity,” said Martin
Wabitsch, M.D., professor of medicine and head of the Division of
Pediatric Endocrinology and Diabetes at Ulm University Medical
Center in Germany. “With this authorization, we are reminded of the
importance of genetic testing, so that we can identify and properly
diagnose patients with POMC, PCSK1 or LEPR deficiency obesity and
offer eligible patients IMCIVREE, a pharmacological therapy
designed to address the underlying cause of their disease.”
“With this authorization now in the EU, IMCIVREE becomes the
first and only treatment option available to patients in EU
countries and other territories including Northern Ireland to
address the underlying cause of obesities driven by certain genetic
defects in the melanocortin-4 (MC4) receptor pathway,” said David
Meeker, M.D., Chair, President and Chief Executive Officer of
Rhythm. “This marks an important milestone for people in the EU
member states living with POMC, PCSK1 or LEPR deficiency obesities,
who now may have access to a therapy that has been shown to reduce
hunger and body weight. We look forward to working closely with
health authorities throughout the EU, as we commence the
country-by-country reimbursement process and work to make IMCIVREE
available to eligible patients as rapidly as possible.”
Obesity due to POMC, PCSK1 or LEPR deficiency is an ultra-rare
disease caused by variants in POMC,
PCSK1 or LEPR genes that impair the MC4R pathway,
which is a pathway in the hypothalamus that is responsible for
regulating hunger, energy expenditure and consequently body
weight.i,ii People living with obesity due to POMC, PCSK1 or LEPR
deficiency struggle with extreme, insatiable hunger beginning at a
young age, resulting in early-onset, severe obesity.iii,iv As an
MC4R agonist, IMCIVREE is designed to restore impaired MC4R pathway
activity arising due to genetic deficits upstream of the MC4
receptor.
The EC authorization of IMCIVREE is based on results from the
largest studies conducted to date in obesity due to POMC, PCSK1 or
LEPR deficiency.v In two Phase 3 clinical trials, 80 percent of ten
patients with obesity due to POMC or PCSK1 deficiency achieved
greater than ten percent body weight loss and 45.5 percent of 11
patients with obesity due to LEPR deficiency achieved greater than
10 percent body weight loss after one year of treatment with
IMCIVREE. Additionally, in both studies, significant decreases in
body mass index (BMI) were demonstrated across patients who were 6
to 17 years old at baseline (n=14).
In clinical trials, IMCIVREE was generally well-tolerated. The
most common adverse events were injection site reaction, skin
hyperpigmentation and nausea. Warnings and precautions include
disturbance in sexual arousal, depression and suicidal ideation,
skin pigmentation and darkening of pre-existing nevi.
IMCIVREE (setmelanotide)
IndicationviIn the EU, IMCIVREE is
indicated for the treatment of obesity and the control of hunger
associated with genetically confirmed loss-of-function biallelic
pro-opiomelanocortin (POMC), including PCSK1, deficiency or
biallelic leptin receptor (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.
In the United States, IMCIVREE is
indicated for chronic weight management in adult and pediatric
patients 6 years of age and older with obesity due to
pro-opiomelanocortin (POMC), proprotein convertase subtilisin/kexin
type 1 (PCSK1), or leptin receptor (LEPR) deficiency. The condition
must be confirmed by genetic testing demonstrating variants
in POMC, PCSK1, or LEPR genes that are
interpreted as pathogenic, likely pathogenic, or of uncertain
significance (VOUS).
Limitations of
UseviIMCIVREE should be prescribed and
supervised by physicians with expertise in obesity with underlying
genetic etiology. 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, including obesity associated with other genetic
syndromes and general (polygenic) obesity.
Important Safety
Informationvi
WARNINGS AND
PRECAUTIONS
Disturbance in Sexual
Arousal: Sexual adverse reactions may occur in
patients treated with IMCIVREE. Spontaneous penile erections in
males and sexual adverse reactions in females occurred in clinical
studies with IMCIVREE. Instruct patients who have an erection
lasting longer than 4 hours to seek emergency medical
attention.
Depression and Suicidal
Ideation: 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
behaviors.
Skin Pigmentation and
Darkening of Pre-Existing Nevi: Setmelanotide may
lead to generalized increased skin pigmentation and darkening of
pre-existing nevi 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.
Pediatric
Population: IMCIVREE is not approved for use
in neonates or infants. The safety and efficacy of setmelanotide in
children less than 6 years of age has not yet been established. No
data are available.
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.
ADVERSE REACTIONS
- The most common adverse reactions (incidence ≥23%) were
injection site reactions, skin hyperpigmentation, nausea, headache,
diarrhea, abdominal pain, back pain, fatigue, vomiting, depression,
upper respiratory tract infection, and spontaneous penile
erection.
USE IN SPECIFIC
POPULATIONS
PregnancyThere 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-fetal 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.
Breast-feedingIt 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.
FertilityNo 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 the national reporting system listed in
http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc.
See Full Product
Information for IMCIVREEvi.
About Rhythm
PharmaceuticalsRhythm is a commercial-stage
biopharmaceutical company committed to transforming the treatment
paradigm for people living with rare genetic diseases of obesity.
The Company’s precision medicine, IMCIVREE (setmelanotide), was
approved in November 2020 by the U.S. Food and Drug Administration
(FDA) for chronic weight management in adult and pediatric patients
6 years of age and older with obesity due to POMC, PCSK1 or LEPR
deficiency confirmed by genetic testing and by the European
Commission (EC) in July 2021 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 is the first-ever FDA-approved and EC-authorized
therapy for these rare genetic diseases of obesity. Rhythm is
advancing a broad clinical development program for setmelanotide in
other rare genetic diseases of obesity. The Company is leveraging
the Rhythm Engine and the largest known obesity DNA database - now
with approximately 37,500 sequencing samples - to improve the
understanding, diagnosis and care of people living with severe
obesity due to certain genetic deficiencies. The company is based
in Boston, MA.
Forward-Looking
StatementsThis 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, our expectations
surrounding potential regulatory submissions, approvals and timing
thereof, and our business strategy and plans, including regarding
commercialization of setmelanotide. 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,
the impact of our management transition, 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, 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,
2021 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.
Corporate Contact:David ConnollyHead of
Investor Relations and Corporate CommunicationsRhythm
Pharmaceuticals, Inc.857-264-4280dconnolly@rhythmtx.com
Investor Contact:Hannah DeresiewiczStern
Investor Relations,
Inc.212-362-1200hannah.deresiewicz@sternir.com
Media Contact:Adam DaleyBerry & Company
Public Relations212-253-8881adaley@berrypr.com
US-SET-2100029 07/2021
__________________________i Huvenne H, Duberne B, Clément K,
Poitou C. Rare genetic forms of obesity: clinical approach and
current treatments in 2016. Obes Facts. 2016;9(3):158-173.ii
Ellacott KL, Cone RD. The role of the central melanocortin system
in the regulation of food intake and energy homeostasis: lessons
from mouse models. Philos Trans R Soc Land B Biol Sci.
2006;361(1471):1265-1274.iii 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.iv 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. Nat Genet. 1998;19(2):155-157.v Clément, K., et
al. Efficacy and safety of setmelanotide, an MC4R agonist, in
individuals with severe obesity due to LEPR or POMC deficiency:
single-arm, open-label, multicentre, phase 3 trials. The Lancet
Diabetes & Endocrinology. Online first (2020).
https://doi.org/10.1016/S2213-8587(20)30364-8vi For the full
product information, please see the Summary of Product
Characteristics that can be found on www.ema.europa.eu.
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