Rhythm Pharmaceuticals, Inc. (Nasdaq: RYTM), a commercial-stage
biopharmaceutical company focused on transforming the lives of
patients and their families living with hyperphagia and severe
obesity caused by rare melanocortin-4 receptor (MC4R) pathway
diseases, today announced positive interim results from a Phase 2
clinical trial evaluating setmelanotide, the Company’s MC4R
agonist, for the treatment of severe obesity and hyperphagia in
people living with hypothalamic obesity. Based on the encouraging
results observed, the Company intends to proceed to Phase 3
clinical development following consultation with regulatory
agencies.
“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 M. Jennifer Abuzzahab, M.D.,
McNeely Pediatric Diabetes Center and Endocrine Clinic, Children’s
Minnesota and an investigator on the Phase 2 trial. “I believe
these interim results for setmelanotide represent a major milestone
for the hypothalamic obesity community. In this 16-week trial,
patients receiving setmelanotide achieved a remarkable reduction in
body weight, suggesting this precision therapy has the potential to
transform the care of this rare, acquired obesity.”
As of the data cutoff date of May 6, 2022, 11 patients were
evaluable for assessment, including nine patients who completed 16
weeks of treatment and two patients who discontinued early due to
treatment-related adverse events. Data highlights from an interim
analysis of the full analysis set (N=11) include:
- -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 David Meeker, M.D.,
Chair, President and Chief Executive Officer of Rhythm. “We look
forward to engaging with regulatory agencies to finalize our Phase
3 development plans in the months ahead, as we aim to expand our
reach and make setmelanotide available to the approximately 5,000
to 10,000 people living with hypothalamic obesity in the United
States.”
About the Phase 2 Clinical Trial in Hypothalamic
ObesityThe 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 July 11, 2022.
Rhythm plans to present the full data from the 18 patients enrolled
in this Phase 2 clinical trial at an upcoming medical meeting in
the fall of 2022.
About Hypothalamic ObesityHypothalamic 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 the United States with
approximately 500 new cases each year.
Conference Call InformationRhythm will host a
live conference call and webcast at 8:00 a.m. ET today to discuss
these data. Participants may register for the conference call here.
While not required, it is recommended that participants join the
call ten minutes prior to the scheduled start.
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 PharmaceuticalsRhythm 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 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 living 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.
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 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 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 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 to evaluate setmelanotide in children between the ages of 2
and younger than 6 years old and a Phase 3 trial evaluating a
weekly formulation of setmelanotide in patients actively receiving
daily setmelanotide treatment.
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.
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 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.
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
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