Rhythm Pharmaceuticals Presents New Data from Phase 2 and 3 Trials Evaluating Setmelanotide in Multiple Rare Genetic Diseases of Obesity at the 59th Annual ESPE Meeting
-- New subgroup analysis of Phase 3 data show setmelanotide achieved statistically significant weight loss and hunger reduction compared with placebo at 14 weeks in patients with Bardet-Biedl syndrome --
-- Efficacy results from complete topline analyses of Rhythm’s Phase 2 Basket Study show weight loss and hunger reduction at three months on therapy in patients with SRC1 or SH2B1 deficiency --
-- Data from Phase 2 Basket Study also show clear separation between responders and non-responders in change in weight for adults and in BMI-Z scores for children and adolescents --
The Company and its collaborators delivered three oral presentations and four poster presentations, including:
- a new subgroup analysis of data from the 52-week, Phase 3 trial evaluating setmelanotide in Bardet-Biedl syndrome (BBS) that showed setmelanotide achieved statistically significant weight loss and hunger reduction compared to minimal effect observed with placebo during a 14-week, double-blind treatment period;
- complete topline analyses from the exploratory Phase 2 Basket Trial that showed setmelanotide achieved clinically meaningful weight loss or BMI-Z reduction in 30% (9 of 30) of study participants with obesity due to variants of the SRC1 gene; and
- complete topline analyses from the exploratory Phase 2 Basket Trial that showed setmelanotide achieved clinically meaningful weight loss or BMI-Z reduction in 43% (15 of 35) of study participants with obesity due to variants of the SH2B1 gene, including 16p11.2 chromosomal deletions.
“We know from decades of study that reduced activation of the central melanocortin-4 receptor (MC4R) pathway can lead to early-onset, severe obesity and a pathological hunger known as hyperphagia, which characterize rare genetic diseases of obesity,” said Dr.
“In addition to presenting data from our Phase 2 and 3 trials of setmelanotide, we also presented posters at ESPE describing the gene selection process and the design of our Phase 2 DAYBREAK trial,” said
New Subgroup Analysis of Data from Phase 3 Trial in BBS
In a presentation entitled, “Phase 3 Trial of Setmelanotide in Participants with Bardet-Biedl Syndrome: Placebo-Controlled Results,”
- Patients 12 years old or older treated with setmelanotide (n=14) compared to placebo (n=15) at 14 weeks demonstrated an average:
- Greater weight loss of 3.8 kg, or 3%, of their baseline body weight (p<0.05);
- Greater reduction in ‘most hunger score’ of 20.4% from baseline (p<0.05).
- All patients, including those younger than 12 years, treated with setmelanotide (n=16) achieved an average BMI reduction from baseline of 1.5 kg/m2, or 3.8%, greater than patients treated with placebo (n=16) (p<0.05).
In
Rhythm recently submitted a supplemental New Drug Application to the
Complete Topline Analyses from Phase 2 Exploratory Basket Trial SRC1 and SH2B1 Cohorts
Rhythm also presented complete topline data from two genetic cohorts in its exploratory Phase 2 Basket Trial. These proof-of-concept data support the Company’s pivotal EMANATE Phase 3 trial, a randomized, double-blind, placebo-controlled study with five independent sub-studies evaluating setmelanotide in patients with five distinct rare genetic diseases of obesity, including patients whose obesity is linked to certain variants of the SRC1 or SH2B1 genes. Based on genetic sequencing data and setmelanotide response rates achieved in the Basket Trial, Rhythm estimates that the five genetic indications being studied in the EMANATE trial represent a potential addressable patient population of approximately 100,000-200,000 people in
Phase 2 Data in Obesity Due to SRC1 Deficiency
Dr.
- Nine of 30 (30%) of patients achieved a clinically meaningful response to setmelanotide at three months, as defined by weight loss of 5% or greater from baseline, or for patients under 18 years old, a reduction of at least 0.15 in BMI-Z score:
- In adult patients 18 years or older, six of 20 (30%) achieved 5% or greater weight loss at three months;
- In patients younger than 18 years, three of 10 (30%) achieved a BMI-Z reduction of 0.15% or more at three months.
- Across all enrolled patients, the mean overall weight loss from baseline to three months among patients 18 years and older (n=20) was -4.0% (SD: 3.3%), and the mean overall BMI-Z score reduction from baseline to three months among patients younger than 18 years (n=10) was -0.21 (SD: 0.23).
In addition, the data show a clear separation between patients who responded to setmelanotide treatment at three months and those who did not:
- The mean body weight reduction for adult patients who responded (n=6) was 7.9% (90% CI, −9.7 to −6.0), as compared to 2.3% (90% CI, −3.2 to −1.4) for adult patients who did not respond (n=14);
- The mean BMI-Z reduction for patients younger than 18 years who responded (n=3) was 0.48 (90% CI, −0.95 to −0.01), as compared to 0.09 (90% CI, −0.11 to −0.07) for those who did not respond (n=7).
Phase 2 Data in Obesity Due to SH2B1 Deficiency
- Fifteen of 35 (42.9%) of patients achieved a clinically meaningful response to setmelanotide at three months, as defined by weight loss of 5% or greater from baseline, or for patients under 18 years old, a reduction of at least 0.15 in BMI-Z score:
- In patients 18 or older, eight of 22 (36.4%) achieved 5% or greater weight loss at three months;
- In patients younger than 18 years, seven of 13 (53.8%) achieved a BMI-Z reduction of 0.15% or more at three months.
- Across all enrolled patients, the mean overall weight loss from baseline to three months among patients 18 years and older (n=22) was -3.1% (SD: 3.9%), and the mean overall BMI-Z score reduction from baseline to three months among patients younger than 18 years (n=13) was -0.15 (SD: 0.13).
In addition, the data show a clear separation between patients who responded to setmelanotide treatment at three months and those who did not:
- The mean body weight reduction for adult patients who responded (n=8) was 7.2% (90% CI, −8.6 to −5.8), as compared to 0.8% (90% CI, −1.9 to 0.3) for adult patients who did not respond (n=14);
- The mean BMI-Z reduction for patients younger than 18 years who responded (n=7) was 0.25 (90% CI, −0.29 to −0.21), as compared to 0.03 (90% CI, −0.08 to 0.02) patients younger than 18 years who did not respond (n=7).
As previously reported, setmelanotide was generally well tolerated, with a consistent safety profile across these trials.
Additional Poster Presentations
Four additional abstracts were presented as posters:
- A total of 85.7% of patients in the POMC trial (12/14; p<0.0001) and 53.3% of patients in the LEPR trial (8/15; p<0.0001) achieved ≥10% weight loss from baseline at 52 weeks;
- The mean percent change in body weight from baseline to 52 weeks was −25.8% (SD: 9.7%; p<0.0001) and −12.3% (SD: 7.5%; p<0.0001) in the POMC and LEPR trials, respectively.
All Rhythm’s presentations from ESPE 2021 will be available following the meeting on the Publication and Presentations section of its website: https://www.rhythmtx.com/publications/ .
About Rhythm Pharmaceuticals
Rhythm 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), was approved in
IMCIVREE® (setmelanotide) Indication
In
In the EU and
Limitations of Use
IMCIVREE 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 POPULATIONS
Discontinue 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 and MHRA SmPC for IMCIVREE.
Forward-Looking Statements
This 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, 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 quarterly period ended June 30, 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:
Head of Investor Relations and Corporate Communications
857-264-4280
dconnolly@rhythmtx.com
Investor Contact:
Stern Investor Relations, Inc.
212-362-1200
hannah.deresiewicz@sternir.com
Media Contact:
Berry & Company Public Relations
212-253-8881
adaley@berrypr.com
Source: Rhythm Pharmaceuticals, Inc.