Rhythm Pharmaceuticals, Inc. (Nasdaq: RYTM), a global
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 hosted an R&D event for investors and
analysts, “Rhythm Update on MC4R Pathway Programs.”
During the event, the Company announced new topline data from
its ongoing Phase 3, open-label pediatrics trial evaluating one
year of setmelanotide therapy in patients between the ages of 2 and
younger than 6 years with Bardet-Biedl syndrome (BBS) or
proopiomelanocortin (POMC) or leptin receptor (LEPR) deficiency
obesity and new preliminary data from the first stage of its
exploratory Phase 2 DAYBREAK trial. Rhythm also presented
pre-clinical data on its new drug candidate, RM-718, which is
designed to be a more selective MC4R agonist with weekly
administration, and its plans for Phase 1 clinical development.
The Company hosted Amy Wood, Executive Director and Co-Founder
of the Raymond A. Wood Foundation, and Jennifer Miller, MD,
Professor of Pediatric Endocrinology, University of Florida, who
shared insights on hypothalamic obesity and the severe impact of
the disease on patient quality of life. Rhythm continues to advance
the development of setmelanotide in patients with hypothalamic
obesity and remains on track to complete Phase 3 study enrollment
by the end of 2023.
“Today, we are excited to showcase our commitment to
understanding the MC4R pathway and developing the next generation
of therapies,” said David Meeker, M.D., Chair, President and Chief
Executive Officer of Rhythm. “Setmelanotide has demonstrated its
potential to effect a clinically significant weight loss in
children ages 2 to younger than 6 years old, potentially enabling
us to treat patients younger in life when these diseases first
present. With our DAYBREAK trial, we have shown potential for a
meaningful, positive response to setmelanotide in several new gene
cohorts.”
Setmelanotide demonstrated clinically meaningful
reductions in BMI and BMI-Z score in patients aged 2 to <6
(N=12)Today, Rhythm presented new data from its 52-week,
Phase 3 pediatrics trial in patients between 2 and younger than 6
years old. The hyperphagia and severe obesity of rare
genetically-caused MC4R pathway diseases can present early in life,
and these data show potential efficacy in patients younger than 6.
This trial is a multi-center, one-year, open-label trial in
pediatric patients with obesity due to biallelic POMC, PCSK1 or
LEPR deficiency or a clinical diagnosis of BBS with genetic
confirmation. The primary efficacy endpoint is a responder
analysis, based on the proportion of patients who experience a
decrease from baseline in BMI-Z score of ≥0.2.
Highlights from the data include:
- 83.3% of all patients (10 of 12) achieved ≥ 0.2 reduction in
BMI-Z score from baseline to week 52;
- 18.4 percent mean reduction from baseline in BMI at week 52
(N=12);
- 3.04 mean reduction from baseline in BMI-Z score at week 52
(N=12);
- 11 patients completed the trial, and all remain on therapy, as
of Dec. 5, 2023; one patient discontinued and was lost to
follow-up; and
- The safety profile is consistent with past trials evaluating
setmelanotide.
Rhythm today also announced it has 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 pediatric patients between 2 and younger than
6 years old with BBS or POMC, PCSK1 or LEPR deficiency in the
European Union. The Company anticipates submitting a supplementary
New Drug Application (sNDA) to the U.S. Food and Drug
Administration (FDA) in the first half of 2024 seeking a similar
label expansion.
RM-718 demonstrated potential to reduce body weight and
hyperphagia with a favorable safety profile and no
hyperpigmentation in pre-clinical studiesRhythm presented
data from several pre-clinical studies showing that RM-718, a new,
weekly, MC4R-specific agonist, demonstrated the potential to reduce
body weight and hunger with a favorable safety profile. RM-718 is
designed to be more highly targeted and MC1R sparing with the
potential to not cause hyperpigmentation. The Company also showed
data from pre-clinical studies demonstrating that RM-718 had no
off-target cardiovascular effects in non-human primate studies.
Rhythm also announced today that it completed submission of a
new investigational drug application for RM-718 to the FDA. The
Company anticipates beginning Phase 1 in-human trials in the first
half of 2024, including a multiple-ascending dose study in patients
with hypothalamic obesity.
Data from Phase 2 DAYBREAK trial demonstrate potential
efficacy of setmelanotide in multiple genetically-defined
cohortsRhythm today also announced data from the
open-label part of its exploratory Phase 2 DAYBREAK trial that
demonstrate potential efficacy in patients in multiple
genetically-defined cohorts. The Company presented data from the
full analysis set for DAYBREAK, which includes 164 patients. A
total of 112 patients completed the 16-week Stage 1 of the Phase 2
trial, with 52 patients who discontinued.
The primary endpoint of the trial is the proportion of patients
by genotype who achieve a BMI reduction of ≥5% from baseline in
response to setmelanotide at the end of Stage 1. The rates of
response from Stage 1 of the trial were:
- 30% of patients (12 of 40) with variants in the SEMA3 gene
cohort;
- 35.6% of patients (16 of 45) with variants in the PLXNs gene
cohort;
- 56.3% of patients (9 of 16) with variants in the PHIP gene
cohort;
- 40% of patients (2 of 5) with variants in the TBX3 gene
cohort;
- 30% of patients (3 of 10) with variants in the MAGEL2 gene
cohort; and
- 25% of patients (5 of 20) with variants in the SIM1 gene
cohort.
For those who completed Stage 1, the rates of response of
patients who achieved a BMI reduction of greater than 5% from a
post-hoc analysis were:
- 44.4% of patients (12 of 27) with variants in the PLXNs gene
cohort;
- 61.5% of patients (16 of 26) with variants in the SEMA3 gene
cohort than 5%; and
- 69.2% of patients (9 of 13) with variants in the PHIP gene
cohort.
A total of 49 patients who completed Stage 1 with a response to
setmelanotide were randomized into Stage 2 of the trial. Stage 2 is
a 24-week, double-blind, placebo-controlled withdrawal study. These
patients were stratified into genetically defined cohorts and
randomized 2:1 to receive setmelanotide or placebo.
Rhythm anticipates announcing DAYBREAK Stage 2 data in the
second half of 2024.
Conference Call InformationA live webcast of
the R&D call will be available under "Events and Presentations"
in the Investor Relations section of the Rhythm Pharmaceuticals
website at https://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 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), an MC4R agonist designed to treat hyperphagia and
severe obesity caused by rare MC4R pathway diseases, 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 pro-opiomelanocortin
(POMC), proprotein convertase subtilisin/kexin type 1 (PCSK1) or
leptin receptor (LEPR) deficiency confirmed by genetic testing, or
patients with a clinical diagnosis of Bardet-Biedl syndrome (BBS).
Both the European Commission (EC) and the UK’s Medicines &
Healthcare Products Regulatory Agency (MHRA) have authorized
setmelanotide for the treatment of obesity and the control of
hunger associated with genetically confirmed BBS or genetically
confirmed loss-of-function biallelic POMC, including PCSK1,
deficiency or biallelic LEPR deficiency in adults and children 6
years of age and above. Additionally, Rhythm is advancing a broad
clinical development program for setmelanotide in other rare MC4R
pathway diseases, as well as a preclinical suite of small molecules
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.
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
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 the anticipated timing for initiation of
clinical trials and release of clinical trial data and our
expectations surrounding potential regulatory submissions,
approvals and timing thereof, including for our Phase 2 DAYBREAK
trial, anticipated development plan for RM-718 and regulatory
submissions for our Phase 3 pediatrics program, our business
strategy and plans, including regarding commercialization of
setmelanotide in the United States and Europe, the application of
genetic testing and related growth potential, and expectations
surrounding the potential market opportunity for our product
candidates.. Statements using word such as “expect”, “anticipate”,
“believe”, “may”, “will”, "aim" and similar terms are also
forward-looking statements. Such statements are subject to numerous
risks and uncertainties, including, but not limited to, risks
relating to our liquidity and expenses, our ability to enroll
patients in clinical trials, the design and outcome of clinical
trials, the ability to achieve necessary regulatory approvals,
risks associated with data analysis and reporting, failure to
identify and develop additional product candidates, unfavorable
pricing regulations, third-party reimbursement practices or
healthcare reform initiatives, risks associated with the laws and
regulations governing our international operations and the costs of
any related compliance programs, the impact of competition, risks
relating to product liability lawsuits, inability to maintain our
collaborations, or the failure of these collaborations, our
reliance on third parties, risks relating to intellectual property,
our ability to hire and retain necessary personnel, 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, failure to realize
the anticipated benefits of our acquisition of Xinvento B.V. or
significant integration difficulties related to the acquisition,
and the other important factors discussed under the caption “Risk
Factors” in our Quarterly Report on Form 10-Q for the quarter ended
September 30, 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 ConnollyExecutive
Director, Investor Relations and Corporate CommunicationsRhythm
Pharmaceuticals, Inc.857-264-4280dconnolly@rhythmtx.com
Media Contact:Adam DaleyBerry & Company
Public Relations212-253-8881adaley@berrypr.com
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