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 Medicines Agency’s (EMA) Committee for
Medicinal Products for Human Use (CHMP) has adopted a positive
opinion, recommending marketing authorization for setmelanotide for
the treatment of obesity and the control of hunger associated with
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.
“People living with these rare genetic diseases experience
early-onset, rapid weight gain and severe, insatiable hunger, and,
despite significant effort to control their weight and appetite
with supportive care and lifestyle interventions, patients often
regain weight after any short-term period of weight loss,” said
Karine Clément, M.D., Ph.D., Professor of Nutrition at
Pitié-Salpêtrière Hospital, Sorbonne Université and Head of the
INSERM Nutriomics Laboratory in Paris. “With this positive opinion
based on data from the largest clinical trials to date in these
patient populations, people living with POMC, PCSK1 or LEPR
deficiency obesities in Europe may soon have a therapeutic option
with the potential to reduce their hunger and body weight.”
The CHMP opinion on setmelanotide, which has the PRIority
MEdicines (PRIME) designation, will now be reviewed by the European
Commission. A final decision on the marketing authorization
application for setmelanotide is anticipated in July 2021. If
approved by the European Commission, setmelanotide would be
the first treatment in the EU indicated for these rare genetic
diseases of obesity and would be commercialized under the brand
name IMCIVREE™.
“We are excited by this positive opinion from the CHMP, which
marks a significant step toward bringing setmelanotide to patients
suffering from the severe obesity and insatiable hunger associated
with rare genetic diseases of obesity around the world,” said David
Meeker, M.D., Chair, President and Chief Executive Officer of
Rhythm. “We look forward to the European Commission’s decision in
the coming months, as we continue to build our global
infrastructure to support commercial availability and broaden our
ongoing clinical development program to explore setmelanotide’s
potential in other rare genetic diseases of obesity.”
Pivotal Trials and Data Supporting Positive
OpinionPOMC, PCSK1 or LEPR deficiency obesities are
ultra-rare diseases caused by variants in POMC, PCSK1 or LEPR genes
that impair the MC4 receptor pathway, which is a pathway in the
hypothalamus that regulates hunger, energy expenditure and,
consequently, body weight. 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.
As an MC4 receptor agonist, setmelanotide is designed to restore
impaired MC4 receptor pathway activity arising due to genetic
deficits upstream of the MC4 receptor.
The CHMP based its positive opinion on the results from two
pivotal trials in which setmelanotide achieved statistically
significant and clinically meaningful weight loss and reduction in
hunger in patients with POMC, including PCSK1, and LEPR deficiency
obesity. Across both studies, statistically significant and
clinically meaningful reductions in body mass index (BMI) for
adults and BMI-Z scores, which represent the number of standard
deviations from median BMI by child age and sex, were achieved.
These two studies, which are the largest studies conducted in these
disease states to date, were identically designed one-year,
open-label studies, each with a double-blind, placebo-controlled
withdrawal period. Additional supportive data were gathered in an
investigator-led study and an ongoing extension study.
Pivotal Data in POMC, including PCSK1, Deficiency
Obesity
- Eight of 10 patients with POMC deficiency obesity achieved the
primary endpoint of greater than 10 percent weight loss over
approximately one year (p<0.0001);
- 50 percent of patients in the trial met or exceeded a 25
percent improvement in self-reported hunger scores (p=0.0004);
- Mean reduction from baseline in body weight was -25.6 percent
(p<0.0001);
- Mean reduction from baseline in most hunger rating was -27.1
percent (p=0.0005);
- Mean weight loss was 32 kg, or 70.5 pounds, over one year on
therapy.
Pivotal Data in LEPR Deficiency Obesity
- Five of 11 patients with LEPR deficiency obesity achieved the
primary endpoint of greater than 10 percent weight loss over
approximately one year (p=0.0001);
- 73 percent of patients in the trial met or exceeded a 25
percent improvement in self-reported hunger scores
(p<0.0001);
- Mean reduction from baseline in body weight was -12.5 percent
(p<0.0001);
- Mean reduction from baseline in most hunger rating was -43.7
percent (p<0.0001);
- Mean weight loss was 16.7 kg, or 36.8 pounds, over one year on
therapy.
In both studies, significant decreases in BMI were demonstrated
across patients who were 6 to 17 years old at baseline (n=14). As
these patients had not yet completed their growth, appropriate
progression in pubertal development and increases in height were
observed during the study period.
In addition, both studies included a four-week placebo
withdrawal period to further illustrate the effect of treatment
with setmelanotide, during which participants almost immediately
gained weight and experienced an increase in hunger, reversing the
downward trends in weight loss and hunger scores observed during
the first 12 weeks of the treatment period.
Consistent with prior clinical experience, setmelanotide was
generally well tolerated in both trials. Treatment-emergent related
adverse events (AEs) included injection site reactions, nausea and
vomiting, headache, and increased hyperpigmentation (darkening of
the skin). There were no reports of cardiovascular AEs related to
setmelanotide.
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), has
been 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 obesity due to POMC, PCSK1 or LEPR deficiency
confirmed by genetic testing. IMCIVREE is the first-ever FDA
approved 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.
IMCIVREE™ (setmelanotide)
IndicationIMCIVREE is indicated for chronic weight
management in adult and pediatric patients 6 years of age and older
with obesity due to proopiomelanocortin (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 (VUS).
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, including obesity associated with other genetic
syndromes and general (polygenic) obesity.
Important Safety
Information
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: Some drugs that target the central nervous
system, such as IMCIVREE, may cause depression or suicidal
ideation. Monitor patients for new onset or worsening of
depression. Consider discontinuing IMCIVREE if patients experience
suicidal thoughts or behaviors.
Skin Pigmentation and
Darkening of Pre-Existing Nevi: IMCIVREE may cause
generalized increased skin pigmentation and darkening of
pre-existing nevi due to its pharmacologic effect. This effect is
reversible upon discontinuation of the drug. Perform a full body
skin examination prior to initiation and periodically during
treatment with IMCIVREE to monitor pre-existing and new skin
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.
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
POPULATIONSDiscontinue IMCIVREE when pregnancy is
recognized unless the benefits of therapy outweigh the potential
risks to the fetus.
Treatment with IMCIVREE is not
recommended for use while breastfeeding.
To report SUSPECTED ADVERSE REACTIONS,
contact Rhythm Pharmaceuticals at +1 (833) 789-6337 or
FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
See Full Prescribing
Information for IMCIVREE.
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
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