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 data that showed meaningful weight loss
was sustained and progressed in patients with hypothalamic obesity
treated with setmelanotide for six months as part of the long-term
extension of its Phase 2 trial.
“Hypothalamic obesity is a challenging disease to manage with
patients generally refractory to standard treatments for obesity.
The setmelanotide results to date have been remarkable with
setmelanotide demonstrating sustained and deepening reductions in
multiple body mass index (BMI) measures at six months of treatment,
showing progressive and consistent improvement over previously
reported 16-week BMI reduction data,” said Christian Roth, M.D.,
Seattle Children’s Research Institute and Division of
Endocrinology, Department of Pediatrics, University of Washington,
who presented these data during The Endocrine Society Annual
Meeting & Expo (ENDO 2023) being held June 15-18 in Chicago.
“This impressive response adds to the evidence suggesting
setmelanotide may provide a meaningful clinical benefit for
patients with this disease who currently have no approved
therapeutic options.”
Rhythm enrolled 18 patients in its open-label, 16-week Phase 2
trial designed to evaluate setmelanotide in patients with acquired
hypothalamic obesity. Thirteen of those patients1 who enrolled in
the long-term extension trial reached a total of six months or more
on setmelanotide therapy, as of the data cutoff date of Nov. 30,
2022. Highlights from the data presented show:
- 21.0 mean percent reduction in BMI at month 6 from baseline,
which progressed from 16.8 mean percent reduction in BMI at week 16
across these 13 patients;
- 10 of 13 (76.9%) patients achieved 10% BMI reduction or greater
at month 6 and all 13 patients achieved 5% BMI reduction or
greater;
- 9.2 kg (23.9%) and 3.0 kg (6.3%) mean decreases observed in fat
mass and lean muscle mass, respectively, at week 16 in pediatric
patients (n=11); and
- 1.7 point mean decrease from baseline in BMI-Z score from
baseline in patients younger than 18 (n=11).
In addition, Rhythm presented data demonstrating that all
patients achieved improvement in severity of their obesity, and 10
of 13 patients achieved an improvement in weight classification by
one or more class, as defined by the U.S. National Institutes of
Health and the World Health Organization, which characterize
obesity classes based on BMI2. Among pediatric patients, there was
a 34.3 percentage point decrease in the 95th percentile at month 6,
which corresponds to an average move from morbid obesity to mild
obesity.
Consistent with prior clinical experience in other rare MC4R
pathway diseases, setmelanotide was observed to be generally well
tolerated and no new safety concerns were observed in the long-term
extension trial, as of the cutoff date Nov. 30, 2022.
Additional presentationsRhythm and its
collaborators presented three additional posters at ENDO 2023:
As presented in a poster titled, “Treatment History and
Comorbidities Reported by Patients with Hypothalamic Obesity
Treated with Setmelanotide in a Phase 2 Trial,” 78% of patients
with hypothalamic obesity who had participated in that trial had
attempted and failed lifestyle modifications, such as diet
modification and calorie restriction, before enrolling in this
trial. A total of nine patients had used and failed to achieve
weight loss with pharmacotherapies, including seven who tried using
multiple anti-obesity medications.
Data presented on a poster entitled, “Effect of Setmelanotide on
Metabolic Parameters and Vital Signs in a Phase 2 Trial of Patients
with Hypothalamic Obesity,” showed that most patients experienced
reduction in waist circumference with favorable changes in body
composition and no adverse changes in metabolic, glycemic, or vital
sign parameters.
Also presented was, “Trial Design of a Double-blind, Randomized,
Placebo-Controlled, Phase 3 Study of Setmelanotide in Patients with
Hypothalamic Obesity.” This ongoing pivotal trial is designed to
enroll 120 patients 4 years old or older randomized 2:1 to
setmelanotide therapy or placebo for a total of 60 weeks, including
up to eight weeks for dose titration. The primary endpoint is the
percent change in BMI after approximately 52 weeks on a therapeutic
regimen of setmelanotide versus placebo. Rhythm expects to complete
patient enrollment in the first quarter of 2024.
All Rhythm’s presentations from ENDO will be available on the
Publications and Presentations section of its website:
https://www.rhythmtx.com/publications/.
About Hypothalamic ObesityHypothalamic obesity
is a rare, acquired form of extreme obesity that occurs following
damage to the hypothalamic region of the brain, which includes the
MC4R pathway and 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, and 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 U.S. with approximately 500
new cases each year. There are no FDA approved therapies for
hypothalamic obesity.
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) diseases. Rhythm’s lead asset, IMCIVREE®
(setmelanotide) is approved by the U.S. Food and Drug
Administration (FDA) and authorized by the European Commission (EC)
and the UK’s Medicines & Healthcare Products Regulatory
Agency (MHRA) for use in accordance with product labeling.
Additionally, Rhythm is advancing a broad clinical development
program for setmelanotide in other rare MC4R pathway diseases, as
well as a preclinical suite of investigational candidates for the
treatment of congenital hyperinsulinism. Rhythm’s headquarters is
in Boston, MA.
Setmelanotide IndicationIn the United
States, setmelanotide 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 BBS.
In the European Union, setmelanotide is indicated for the
treatment of obesity and the control of hunger associated with
genetically confirmed Bardet-Biedl syndrome (BBS) or genetically
confirmed loss-of-function biallelic proopiomelanocortin (POMC),
including PCSK1, deficiency or biallelic leptin receptor (LEPR)
deficiency in adults and children 6 years of age and above.
In Canada, setmelanotide is indicated for the treatment of
obesity due to Bardet-Biedl syndrome (BBS) or genetically-confirmed
biallelic pro-opiomelanocortin (POMC), proprotein convertase
subtilisin/kexin type 1 (PCSK1), or leptin receptor (LEPR)
deficiency due to variants interpreted as pathogenic, likely
pathogenic, or of uncertain significance in adults and children 6
years of age and above.
Limitations of UseIn the United
States and Europe, Setmelanotide should be prescribed and
supervised by a physician with expertise in obesity with underlying
genetic etiology.
Setmelanotide is not indicated for the treatment of patients
with the following conditions as setmelanotide 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
Skin Monitoring: Setmelanotide may lead to
generalized 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 setmelanotide. Consideration should be given to
discontinuing setmelanotide if patients experience suicidal
thoughts or behaviors.
Pediatric 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.
Sodium: This medicinal product contains
less than 1 mmol sodium (23 mg) per dose, that is to say
essentially “sodium-free.”
ADVERSE REACTIONSThe most frequent adverse
reactions are hyperpigmentation (51%), injection site reaction
(39%), nausea (33%), and headache (26%).
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, setmelanotide
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 setmelanotide 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 Rhythm
Pharmaceuticals at +1 (833) 789-6337. See Summary of
Product Characteristics’ APPENDIX V for a list of
European national reporting systems to communicate adverse
reactions.
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 U.S. 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, the long term extension
trial, and the anticipated timing of a Phase 3 trial, the potential
benefits of setmelanotide for patients, including those with
hypothalamic obesity, and our expectations surrounding potential
regulatory submissions, approvals and timing thereof, our business
strategy and plans, including regarding commercialization of
setmelanotide, 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 and general economic conditions 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 three months ended March 31, 2023 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
1 Six-month data is not available for a 14th patient who
transitioned from the Phase 2 trial and enrolled in the open-label,
long-term extension trial was lost to follow up. This patient has
reentered the long-term extension trial and was undergoing dose
escalation as of Nov. 30, 2022.
2 Class III – BMI ≥ 40 kg/m2 (also referred to as
severe, extreme, or massive obesity); Class II – BMI 35
to 39.9 (severe obesity); Class I – BMI 30 to 34.9 (mild
obesity); In pediatric patients, all three obesity classes are
≥95th percentile.
(https://www.nhlbi.nih.gov/health/overweight-and-obesity/symptoms)
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