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 U.S. Food and Drug Administration (FDA) has
approved the Company’s supplemental New Drug Application (sNDA) for
IMCIVREE® (setmelanotide), a melanocortin-4 receptor (MC4R)
agonist, for patients with Bardet-Biedl syndrome (BBS).
With today’s approval, IMCIVREE is indicated for chronic weight
management in adult and pediatric patients 6 years old and older
with monogenic or syndromic obesity due to proopiomelanocortin
(POMC), proprotein convertase subtilisin/kexin type 1 (PCSK1) or
leptin receptor (LEPR) deficiency, or BBS.
“This FDA approval represents a significant milestone for
Rhythm, validating our strategy of developing IMCIVREE for people
with hyperphagia and severe obesity caused by rare MC4R-pathway
diseases and allowing us to provide our precision therapy to an
established community of patients living with BBS and their
families who are eagerly awaiting a new treatment option,” said
David Meeker, M.D., Chair, President and Chief Executive Officer of
Rhythm. “Leveraging the robust infrastructure we put in place
following the initial approval of IMCIVREE for obesity due to
biallelic POMC, PCSK1 or LEPR deficiency and our new high-touch
patient support services to assist patients throughout the journey
from diagnosis to ongoing treatment, we are able to make IMCIVREE
available for BBS immediately. We look forward to delivering this
important medicine to the growing community of patients and
families in need of options that can effectively address the
obesity and hyperphagia that affect many people living with
BBS.”
IMCIVREE was initially approved by the FDA in November 2020 for
chronic weight management in adult and pediatric patients 6 years
of age and older with obesity due to POMC, PCSK1 or LEPR
deficiency. IMCIVREE’s label was updated today to include an
FDA-approved test developed under a post-marketing commitment to
confirm variants in POMC, PCSK1 or LEPR genes
that are interpreted as pathogenic, likely pathogenic, or of
uncertain significance (VUS).
IMCIVREE is not indicated for the treatment of patients with
obesity due to suspected POMC, PCSK1 or LEPR deficiency with POMC,
PCSK1 or LEPR variants classified as benign or likely benign, or
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.
In clinical trials, IMCIVREE was generally well-tolerated.
Disturbance in sexual arousal, depression and suicidal ideation,
increased skin pigmentation and darkening of pre-existing nevi, and
benzyl alcohol toxicity in neonates and low birth-weight infants
may occur. The most common adverse reactions were skin
hyperpigmentation, injection site reactions and nausea.
BBS is a rare genetic disease that affects approximately
1,500-2,500 people in the U.S. People living with BBS may
experience insatiable hunger, also known as hyperphagia, and severe
obesity beginning early in life. BBS may also be associated with
cognitive impairment, polydactyly, renal dysfunction, hypogonadism,
and visual impairment.
Robert Haws, M.D., a BBS expert who recently retired from his
role as Director of the Center of Excellence for Bardet-Biedl
Syndrome at the Marshfield Clinic Research Institute in Wisconsin,
said, “This approval marks an important achievement for the entire
BBS community including patients and their families, clinicians and
researchers, as we all have been looking forward to a therapy that
addresses the burdens of hyperphagia and severe obesity that
significantly affect daily lives of patients and caregivers living
with BBS. IMCIVREE achieved significant reductions in weight and
hunger in patients with BBS, providing this community a much needed
and first-ever therapeutic option.”
“It is important to understand that the early-onset, severe
obesity and pathologic hunger experienced by many people living
with BBS can be debilitating, especially when you consider the
impact of food-seeking behavior on families,” said Timothy Ogden,
President, BBS Foundation and Family Association. “Challenges in
managing weight and hunger have dramatically negative effects on
health, well-being, and quality of life for those living with BBS,
and we are thrilled finally to have a new treatment option to
address this significant unmet need.”
Data from Phase 3 trial evaluating IMCIVREE in
BBS The FDA application for IMCIVREE was based on data
from Rhythm’s pivotal Phase 3 clinical trial, which was the largest
and longest interventional clinical trial in BBS. In the clinical
trial, IMCIVREE delivered early, significant and sustained weight
reduction. The trial met its primary endpoint and all key secondary
endpoints, with statistically significant reductions in weight and
hunger at 52 weeks on therapy.
As presented in the label, in patients aged ≥6 years with
obesity due to BBS (N=31):
- Mean percent change in BMI was -7.9% without requirements for
diet and exercise;
- Placebo-adjusted change in BMI was -4.5% in a 14-week
double-blind placebo-controlled stage (IMCIVREE n=22; -4.6% change
in BMI; placebo n=22; -0.1% change in BMI); and
- Statistically significant mean change in hunger score was -2.1
at 52 weeks in patients 12 years and older who were able to
self-report their hunger (n=14).
Rhythm also announced that the FDA issued a complete response
letter for the sNDA for setmelanotide in Alström syndrome. Rhythm
plans to reevaluate potential paths forward in Alström syndrome in
the U.S.
“We appreciate the FDA’s careful review of our sNDA for IMCIVREE
for the treatment of Alström syndrome, but are disappointed in this
outcome,” added Dr. Meeker. “We are tremendously grateful to the
Alström syndrome patients, caregivers and physicians who
participated in our clinical development efforts and look forward
to providing an update regarding our path forward.”
Rhythm InTune offers personalized support to patients,
caregivers and physiciansToday, the Company also announced
the launch of Rhythm InTune, a program that provides personalized
support for individuals living with rare genetic diseases of
obesity. Rhythm InTune provides education and resources tailored to
fit each patient’s unique need, with a dedicated patient education
manager as a single point of contact. Rhythm InTune is designed to
provide ongoing treatment support to patients who opt in by
educating patients and their health care providers, navigating
insurance coverage as they start treatment, providing injection
support and offering education on what to expect. For more
information, contact patientsupport@rhythmtx.com.
Conference call informationRhythm
Pharmaceuticals will host a live conference call and webcast at
5:00 p.m. ET today to discuss the FDA approval of IMCIVREE for
patients with BBS. The conference call may be accessed by dialing
(844) 498-0570 (domestic) or (409) 983-9726 (international) and
referring to conference ID 2782343. A webcast of the call will be
available under "Events and Presentations" in the Investor
Relations section of the Rhythm Pharmaceuticals website at
http://ir.rhythmtx.com/. The archived webcast will be available on
Rhythm Pharmaceuticals’ website approximately two hours after the
conference call and will be available for 30 days following the
call.
About SetmelanotideSetmelanotide 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 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 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 European Medicines
Agency (EMA) for the treatment of obesity and control of
hyperphagia in adult and pediatric patients 6 years of age and
older with BBS is under review. The Company is also continuing to
advance the most comprehensive clinical research program ever
initiated in MC4R pathway diseases, including the pivotal Phase 3
EMANATE clinical trial evaluating setmelanotide in four independent
sub-studies in patients with obesity due to POMC insufficiency
caused by heterozygous variants in the POMC or PCSK1 genes, LEPR
insufficiency caused by heterozygous variants in the LEPR gene,
SRC1 deficiency caused by a variant in the NCOA1 gene, and SH2B1
deficiency caused by a variant in the SH2B1 gene or 16p11.2
deletion encompassing the SH2B1 gene. The Phase 2 DAYBREAK trial is
evaluating setmelanotide in patients with severe obesity and
hyperphagia caused by rare variants associated with 10 prioritized
MC4R-relevant genes. Rhythm has also initiated a Phase 3 pediatric
trial and a Phase 3 trial evaluating a weekly formulation of
setmelanotide.
IMCIVREE®
(setmelanotide) IndicationIn 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 UseIMCIVREE 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
Nevi: Generalized increased skin pigmentation and
darkening of pre-existing nevi have occurred. Perform a full body
skin examination prior to initiation and periodically during
treatment to monitor pre-existing and new pigmentary lesions.
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.
ADVERSE REACTIONS
- 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 POPULATIONSTreatment 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 Rhythm
Pharmaceuticals at 833-789-6337 or FDA at 1-800-FDA-1088 or
www.fda.gov/medwatch.
Please see the full Prescribing Information for
additional Important Safety Information.
About Rhythm PharmaceuticalsRhythm is a
commercial-stage biopharmaceutical company committed 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 U.S. Food and Drug
Administration (FDA) 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 confirmed
by genetic testing, or patients with a clinical diagnosis of
Bardet-Biedl syndrome (BBS). The European Commission (EC) and Great
Britain’s Medicines & Healthcare Products Regulatory Agency
(MHRA) have authorized IMCIVREE 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- and
MHRA-authorized therapy for patients with these rare genetic
diseases of obesity. The Company submitted a Type II variation
application to the European Medicines Agency seeking regulatory
approval and authorization for setmelanotide to treat obesity and
control of hunger in adult and pediatric patients 6 years of age
and older with BBS in the European Union. Additionally, Rhythm is
advancing a broad clinical development program for setmelanotide in
other rare genetic diseases of obesity and is leveraging the Rhythm
Engine and the largest known obesity DNA database -- now with
approximately 45,000 sequencing samples -- to improve the
understanding, diagnosis and care of people living with severe
obesity due to certain genetic deficiencies. Rhythm’s headquarters
is 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, including with
respect to our ongoing DAYBREAK, EMANATE, Phase 3 pediatric trials
and Phase 3 weekly switch trials, our expectations surrounding
potential regulatory submissions, approvals and timing thereof,
including from the U.S. FDA and EMA, our business strategy and
plans, including regarding commercialization of IMCIVREE, and our
participation in upcoming events and presentations. 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 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, 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.
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
A photo accompanying this announcement is available at
https://www.globenewswire.com/NewsRoom/AttachmentNg/ab80a1b3-b17d-409d-9943-2d4737f91ae7
Rhythm Pharmaceuticals (NASDAQ:RYTM)
Historical Stock Chart
From Sep 2024 to Oct 2024
Rhythm Pharmaceuticals (NASDAQ:RYTM)
Historical Stock Chart
From Oct 2023 to Oct 2024