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 new data from the Company’s long-term extension (LTE)
trial, which show continued body mass index (BMI) and weight
reductions in patients with SH2B1 or SRC1 deficiency obesity, or
with POMC or LEPR insufficiency obesity (heterozygous). Rhythm and
its collaborators delivered these data in one oral presentation and
two posters at the Endocrine Society Annual Meeting & Expo
(ENDO), being held June 11-14, 2022 in Atlanta.
“We are excited to share initial data from the LTE trial
evaluating setmelanotide in patients with obesity due to SRC1 or
SH2B1 deficiency, or POMC or LEPR insufficiency caused by
heterozygous variants in the POMC, PCSK1, or LEPR genes,” said
David Meeker, M.D., Chair, President and Chief Executive Officer of
Rhythm. “Consistent with our experience in other rare genetic
diseases of obesity, these data demonstrate that ongoing treatment
with setmelanotide delivers continued improvement in weight-related
measures. Importantly, these data also reinforce our confidence in
the design of the placebo-controlled Phase 3 EMANATE clinical
trial, for which we are enrolling patients with each of these
genetic variants, in hopes of focusing on those patient populations
with impaired signaling in the melanocortin-4 receptor (MC4R)
pathway who have highest probability of responding to our precision
therapy, setmelanotide. We continue to enroll patients in EMANATE,
which, if successful, will support our ability to make
setmelanotide available to many more people living with rare
genetic diseases of obesity.”
SH2B1 Deficiency ObesityA total of 19 patients
with obesity due to SH2B1 deficiency caused by a variant in the
SH2B1 gene or 16p11.2 deletion encompassing the SH2B1 gene (SH2B1
deficiency obesity) who were treated with setmelanotide in the
Phase 2 Basket Trial continued into the LTE trial. These data were
presented in a poster, “Body Mass Index and Weight Reduction in
Patients with SH2B1 Deficiency Obesity After 1 Year of
Setmelanotide,” by Sadaf Farooqi, M.D., Ph.D, the Wellcome-MRC
Institute of Metabolic Science at the University of Cambridge.
Highlights include:
- Nineteen (19) patients with SH2B1 deficiency entered the LTE
trial, with 19, 15, and 14 of those patients having received at
least 6, 9, and 12 months of treatment as of Oct. 29, 2021,
respectively.
- Across all patients, including those who did not achieve 5%
weight loss in the Phase 2 Basket Trial but chose to enter the LTE,
the mean (SD) percent change in BMI was −3.4% (8.1%; n=19), −5.9%
(10.0%; n=15), and −9.7% (8.0%; n=14) at 6, 9, and 12 months on
therapy, respectively;
- Responders were defined as patients who achieved ≥5% weight
loss at Month 3:
- Across responders, the mean percent change in BMI was -8.8%
(n=8), -9.1% (n=9) and -12.3% (n=9) at 6, 9 and 12 months on
therapy, respectively; and
- Across non-responders, the mean percent change in BMI was 0.6%
(n=11), -1.1% (n=6) and -4.9% (n=5) at 6, 9 and 12 months on
therapy, respectively.
- Seventeen (17) patients were continuing to receive
setmelanotide therapy in the LTE trial as of the data cut off,
while two patients had discontinued voluntarily. No patients
discontinued due to adverse events.
SRC1 Deficiency ObesityA total of 17 patients
with obesity due to SRC1 deficiency caused by a variant in the
NCOA1 gene who were treated with setmelanotide in Rhythm’s
exploratory Phase 2 Basket Trial continued into the LTE trial.
These data were presented in a poster, “Body Mass Index and Weight
Reductions in Patients with SRC1 Deficiency Obesity After 1 Year of
Setmelanotide,” by Jesús Argente, M.D., Ph.D., Universidad Autónoma
de Madrid in Spain. A deficiency in the SRC1 protein may be due to
a variant on the NCOA1 gene. Highlights include:
- Seventeen (17) patients with SRC1 deficiency entered the LTE
trial, with 18, 13 and 10 of those patients having received at
least 6, 9, and 12 months of treatment as of Oct. 29, 2021,
respectively.
- Across all patients, including those who did not achieve 5%
weight loss in the Phase 2 Basket Trial but chose to enter the LTE,
the mean (SD) percent change in BMI was −5.7% (5.6%; n=16), −7.8%
(5.8%; n=11), and −10.1% (9.4%; n=8) at 6, 9, and 12 months on
therapy, respectively;
- Responders were defined as patients who achieved ≥5% weight
loss at Month 3:
- Across responders, the mean percent change in BMI was -10.1%
(n=7), -10.5% (n=6) and -14.3% (n=3) at 6, 9 and 12 months on
therapy, respectively; and
- Across non-responders, the mean percent change in BMI was -2.3%
(n=9), -4.7% (n=5) and -7.5% (n=5) at 6, 9 and 12 months on
therapy, respectively.
- Fifteen (15) of 17 patients with SRC1 deficiency were
continuing to receive setmelanotide therapy in the LTE trial as of
the data cut off, while two patients had discontinued voluntarily.
No patients discontinued due to adverse events.
POMC or LEPR insufficiency obesity
(heterozygous)A total of 17 patients with obesity caused
by heterozygous variants in the POMC, PCSK1 or LEPR genes who were
treated with setmelanotide in the Phase 2 Basket Trial continued
into the LTE trial. These data were delivered orally by Brieana
Buckley, PharmD, M.S., Vice President of Medical Affairs at Rhythm,
in a presentation entitled, “Body Mass Index and Weight Reductions
in Patients with Obesity Due to Heterozygous Variants in POMC,
PCSK1, or LEPR After 1 Year of Setmelanotide.” Highlights
include:
- Seventeen (17) patients with POMC or LEPR insufficiency obesity
reached 12 months on therapy as of Oct. 29, 2021.
- Across all patients, the mean (SD) percent change in BMI was
−7.9% (7.2%; n=16), -9.0% (8.6%; n=17), and −8.7% (8.2%; n=17) at
6, 9, and 12 months on therapy, respectively; and
- Patients 18 years old and older (n=15) achieved a mean (SD)
percent change in body weight of −8.9% (6.8%; n=15), −11.7% (7.3%;
n=14), and −10.2% (7.9%; n=15) at 6, 9, and 12 months on therapy,
respectively; and
- 53.3% of patients 18 years old and older achieved greater than
10% weight loss at 12 months on therapy.
- Seventeen (17) patients with POMC or LEPR insufficiency obesity
reached 12 months on therapy as of Oct. 29, 2021. Fifteen of those
patients had enrolled in the LTE, five of those patients had
discontinued voluntarily, and two patients who reached 12 months on
therapy in the Basket Trial did not opt into the LTE. No patients
discontinued due to adverse events.
Consistent with prior clinical observations, setmelanotide was
generally well tolerated in the LTE trial across all indications
and no new safety signals were observed.
Phase 3 EMANATE Trial DesignDr. Farooqi also
presented a poster entitled, “Setmelanotide in Patients With
Obesity Due to Heterozygous Variants in POMC, LEPR, NCOA1, or SH2B1
Genes: Design of EMANATE—a Placebo-Controlled Phase 3 Trial.” As
described in the poster, the EMANATE trial is comprised of four
independent sub-studies evaluating setmelanotide in patients with:
POMC insufficiency obesity, LEPR insufficiency obesity, SRC1
deficiency obesity and SH2B1 deficiency obesity. Rhythm plans to
enroll approximately 400 patients with hyperphagia and obesity that
began in early childhood in this trial. In each of the four
sub-studies, patients will be randomized one-to-one to daily
setmelanotide or placebo. The primary efficacy endpoint in each
sub-study is the mean change from baseline to 52 weeks in body
weight, assessed as percent change in BMI in response to
setmelanotide compared to placebo. The first patient was enrolled
in April 2022 and Rhythm anticipates 12-18 months to enroll the
trial.
All Rhythm’s presentations from ENDO will be available on the
Publications and Presentations section of its website:
https://www.rhythmtx.com/publications/.
About Rhythm PharmaceuticalsRhythm is a
commercial-stage biopharmaceutical company committed to
transforming the treatment paradigm for people living with rare
genetic diseases of obesity. Rhythm’s precision medicine, IMCIVREE
(setmelanotide), was approved in November 2020 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 and in July and September 2021,
respectively, by the European Commission (EC) and Great
Britain’s Medicines & Healthcare Products Regulatory
Agency (MHRA) 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 supplemental New Drug Application (sNDA) to
the FDA, which was accepted for filing in November
2021 and is currently assigned a Prescription Drug User Fee
Act (PDUFA) goal date of June 16, 2022, for the treatment of
obesity and control of hunger in adult and pediatric patients six
years of age and older with Bardet-Biedl Syndrome (BBS) or Alström
syndrome. 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 also is
under review. 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.
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 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).
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.
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, EU SmPC
and MHRA SmPC 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, 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, 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, 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 quarter 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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