PreventionGenetics Receives FDA Approval for its Companion Diagnostic Genetic Test as a Class II Medical Device

Developed in collaboration with Rhythm Pharmaceuticals, the test is the first FDA-authorized Class II molecular companion diagnostic device

MARSHFIELD, Wis., June 30, 2022 /PRNewswire/ -- PreventionGenetics, a subsidiary of Exact Sciences Corp., announced today that it was recently granted marketing authorization for the POMC/PCSK1/LEPR companion diagnostic (CDx) genetic test as a Class II device by the Center for Devices and Radiological Health (CDRH), a division of the Food and Drug Administration (FDA). PreventionGenetics, an accredited germline DNA testing laboratory offering genetic testing to patients and physicians around the world, developed the test in collaboration with Rhythm Pharmaceuticals, Inc.

The need for a diagnostic test to confirm variants in POMC, PCSK1 or LEPR genes that are interpreted as pathogenic, likely pathogenic, or of uncertain significance (VUS) has been added to the label for IMCIVREE^® (setmelanotide), a product marketed by Rhythm Pharmaceuticals that was approved by the FDA in 2020 for chronic weight management in adult and pediatric patients 6 years of age and older with obesity due to POMC, PCSK1 or LEPR deficiency.

There is an important distinction between general obesity—a multifactorial condition influenced by multiple genes and environmental factors—and diseases of obesity caused by single-gene variants (monogenic).¹ Like many other genetic disorders, monogenic obesity is extremely rare, with a prevalence of less than 4% in individuals with early onset obesity.^2,3 Identifying these patients through genetic testing allows them to be matched with a targeted therapy, helping to provide relief for an otherwise debilitating condition.

"We're proud to play a part in identifying people with severe obesity who may benefit from taking IMCIVREE, the first FDA approved therapy for people with severe obesity potentially caused by certain genetic deficiencies," said Eric Bend, PhD, FACMG, Associate Laboratory Director at PreventionGenetics.  

IMCIVREE is not indicated for the treatment of patients with obesity due to suspected POMC, PCSK1 or LEPR deficiency with POMC, PCSK1 or LEPR variants classified as benign or likely benign, or other types of obesity not related to POMC, PCSK1 or LEPR deficiency, or other approved indications, including obesity associated with other genetic syndromes and general (polygenic) obesity.

In clinical trials, IMCIVREE was generally well-tolerated. Disturbance in sexual arousal, depression and suicidal ideation, increased skin pigmentation and darkening of pre-existing nevi, and benzyl alcohol toxicity in neonates and low birth-weight infants may occur. The most common adverse reactions were skin hyperpigmentation, injection site reactions and nausea.

The POMC/PCSK1/LEPR companion diagnostic (CDx) genetic test is for in vitro diagnostic use only and must be ordered by a qualified professional in accordance with clinical laboratory regulations.  For more information on PreventionGenetics and the Companion Diagnostic test, visit https://www.preventiongenetics.com/sponsoredTesting/Rhythm/CDX.

In the United States, IMCIVREE is indicated 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 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)
• Bardet-Biedl syndrome (BBS)

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, or BBS, including obesity associated with other genetic syndromes and general (polygenic) obesity

Disturbance in Sexual Arousal: Spontaneous penile erections in males and sexual adverse reactions in females have occurred. Inform patients that these events may occur and instruct patients who have an erection lasting longer than 4 hours to seek emergency medical attention.

Depression and Suicidal Ideation: Depression and suicidal ideation have occurred. Monitor patients for new onset or worsening depression or suicidal thoughts or behaviors. Consider discontinuing IMCIVREE if patients experience suicidal thoughts or behaviors, or clinically significant or persistent depression symptoms occur.

Skin Pigmentation and Darkening of Pre-existing Nevi: Generalized increased skin pigmentation and darkening of pre-existing nevi have occurred. Perform a full body skin examination prior to initiation and periodically during treatment to monitor pre-existing and new 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. Serious and fatal adverse reactions including "gasping syndrome" can occur in neonates and low birth weight infants treated with benzyl alcohol-preserved drugs.

• The most common adverse reactions (incidence ≥20%) included skin hyperpigmentation, injection site reactions, nausea, headache, diarrhea, abdominal pain, vomiting, depression, and spontaneous penile erection.

Treatment with IMCIVREE is not recommended when breastfeeding. Discontinue IMCIVREE when pregnancy is recognized unless the benefits of therapy outweigh the potential risks to the fetus.

To report SUSPECTED ADVERSE REACTIONS, contact Rhythm Pharmaceuticals at 833-789-6337 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

1 https://www.ncbi.nlm.nih.gov/books/NBK573068/
2 https://pubmed.ncbi.nlm.nih.gov/15660521/
3  PreventionGenetics diagnostic testing database

Founded in 2004 and located in Marshfield, Wisconsin, PreventionGenetics is a CLIA and ISO 15189:2012 accredited laboratory owned by Exact Sciences. PreventionGenetics delivers high quality genetic testing at fair prices with exemplary service to patients and clinicians around the world, including the comprehensive whole genome sequencing test, PGnome® and whole exome sequencing test, PGxome®.

A leading provider of cancer screening and diagnostic tests, Exact Sciences relentlessly pursues smarter solutions providing the clarity to take life-changing action, earlier. Building on the success of Cologuard and Oncotype tests, Exact Sciences is investing in its product pipeline to support patients before and throughout their cancer diagnosis and treatment. Exact Sciences unites visionary collaborators to help advance the fight against cancer. For more information, please visit the company's website at www.exactsciences.com, follow Exact Sciences on Twitter @ExactSciences, or find Exact Sciences on Facebook.

Rhythm 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. 

NOTE: PGnome and PGxome are registered trademarks of PreventionGenetics, an Exact Sciences Corporation company. All other trademarks and service marks are the property of their respective owners.

This news release contains forward-looking statements concerning our expectations, anticipations, intentions, beliefs or strategies regarding the future. These forward-looking statements are based on assumptions that we have made as of the date hereof and are subject to known and unknown risks and uncertainties that could cause actual results, conditions and events to differ materially from those anticipated. Therefore, you should not place undue reliance on forward-looking statements. Risks and uncertainties that may affect our forward-looking statements are described in the Risk Factors sections of Exact Sciences' most recent Annual Report on Form 10-K and any subsequent Quarterly Reports on Form 10-Q, and in Exact Sciences' other reports filed with the Securities and Exchange Commission. Exact Sciences undertakes no obligation to publicly update any forward-looking statement, whether written or oral, that may be made from time to time, whether as a result of new information, future developments or otherwise.

Exact Sciences
Media Contact: Steph Spanos, [email protected], 608-556-4380
Investor Contact: Megan Jones, [email protected], 608-535-8815
US-SET-2200154 06/2022

SOURCE PreventionGenetics