Approval based on Phase 3 EoE KIDS trial showing a greater proportion of children taking Dupixent achieved histological remission compared to placebo

Expanded indication marks second disease for which Dupixent is approved in children this young, underscoring the commitment to bringing therapies to young patients with significant unmet needs  

EoE is one of five FDA-approved indications for Dupixent in the U.S. for which type 2 inflammation is an underlying driver

TARRYTOWN, N.Y. and PARIS, Jan. 25, 2024 (GLOBE NEWSWIRE) – Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) and Sanofi today announced that the U.S. Food and Drug Administration (FDA) has approved Dupixent^®  (dupilumab) for the treatment of pediatric patients aged 1 to 11 years, weighing at least 15 kg, with eosinophilic esophagitis (EoE). Dupixent is now the first and only medicine approved in the U.S. specifically indicated to treat these patients. This approval expands the initial FDA approval for EoE in May 2022 for patients aged 12 years and older, weighing at least 40 kg. The FDA evaluated Dupixent for this expanded indication under Priority Review, which is reserved for medicines that represent potentially significant improvements in efficacy or safety in treating serious conditions.

EoE is a chronic, progressive disease associated with type 2 inflammation that is thought to be responsible for damaging the esophagus and impairing its function. EoE can severely impact a child’s ability to eat, and they may experience heartburn, vomiting, abdominal discomfort, trouble swallowing, food refusal and failure to thrive. These symptoms can adversely impact their growth and development. Continuous treatment of EoE may be needed to reduce the risk of complications and disease progression. Approximately 21,000 children under the age of 12 in the U.S. are currently being treated for EoE with unapproved therapies. However, the actual prevalence of children with this disease is likely higher, given symptoms can be mistaken for other conditions and there are delays in diagnosis.

“Young children are some of the most vulnerable patients with eosinophilic esophagitis, or EoE, as this debilitating and progressive disease threatens their basic ability to eat. Until today, these children had no approved treatment options specifically for EoE, leaving many with unapproved medicines that failed to target the root cause of their disease,” said George D. Yancopoulos, M.D., Ph.D., Board co-Chair, President and Chief Scientific Officer at Regeneron, and a principal inventor of Dupixent. “With this approval, Dupixent becomes the first and only treatment option for EoE patients aged 1 and older, weighing at least 15 kg. By targeting the underlying type 2 inflammation that contributes to this disease, Dupixent has the potential to transform the standard of care for these children as it has for adults and adolescents with EoE.”

The FDA approval is based on data from the Phase 3 EoE KIDS trial with two parts (Part A and Part B) evaluating the efficacy and safety of Dupixent in children aged 1 to 11 years with EoE. At 16 weeks, 66% of children who received higher dose Dupixent at tiered dosing regimens based on weight (n=32) achieved histological disease remission (≤6 eosinophils/high power field), the primary endpoint, compared to 3% for placebo (n=29). Histological remission was sustained at week 52, with 17 of 32 (53%) children treated with Dupixent in Parts A and B. Histological remission was also achieved at week 52 in 8 of 15 (53%) children who switched to Dupixent from placebo in Part B. In addition, a greater decrease in the proportion of days with one or more signs of EoE based on Pediatric EoE Sign/Symptom Questionnaire-caregiver version (PESQ-C) was observed in children treated with Dupixent at 16 weeks compared to placebo. 

“Young children with eosinophilic esophagitis have significant unmet medical needs; despite existing treatment options, 40% of these children in the U.S. under the age of 12 continue to experience symptoms of this disease,” said Naimish Patel, M.D., Head of Global Development, Immunology and Inflammation at Sanofi. “Today’s approval underscores our commitment to bringing therapies to young patients with unmet needs and also brings hope to these patients who are at a critical age where struggling to eat and maintain weight directly impacts their overall nutritional intake and development.”

The safety profile of Dupixent observed through 16 weeks in children aged 1 to 11 years weighing at least 15 kg was generally similar to the safety profile of Dupixent observed through 24 weeks in adult and pediatric patients aged 12 years and older with EoE. The most common adverse events (≥2%) more frequently observed with Dupixent than placebo were injection site reactions, upper respiratory tract infections, arthralgia (joint pain) and herpes viral infections. In EoE KIDS Part B, one case of helminth infection was reported in the Dupixent arm.

About the Dupixent Pediatric Eosinophilic Esophagitis Trial

The Phase 3 randomized, double-blind, placebo-controlled trial evaluated the efficacy and safety of Dupixent in children aged 1 to 11 years, weighing at least 15 kg, with EoE, as determined by histological, endoscopic and patient- or caregiver-reported measures. At baseline, 97% of these patients had at least one co-existing type 2 inflammatory disease, such as food allergy, allergic rhinitis, asthma and atopic dermatitis.

Part A, a 16-week, double-blind treatment period, enrolled 61 patients and evaluated the safety and efficacy of Dupixent in a tiered, weight-based dosing schema. The primary endpoint was histological disease remission, which was defined as peak esophageal intraepithelial eosinophil count of ≤6 eosinophils (eos)/high power field (hpf). Changes in caregiver-reported symptoms (proportion of days with 1 or more EoE signs [e.g., stomach pain, vomiting, food refusal]) were evaluated using PESQ-C.

Part B was a 36-week extended active treatment period (n=47) in which eligible children from Part A in the Dupixent group continued to receive their dose level and those in the placebo group in Part A switched to Dupixent.

About Dupixent 

Dupixent, which was invented using Regeneron’s proprietary VelocImmune^® technology, is a fully human monoclonal antibody that inhibits the signaling of the interleukin-4 (IL-4) and interleukin-13 (IL-13) pathways and is not an immunosuppressant. The Dupixent development program has shown significant clinical benefit and a decrease in type 2 inflammation in Phase 3 trials, establishing that IL-4 and IL-13 are key and central drivers of the type 2 inflammation that plays a major role in multiple related and often co-morbid diseases. These diseases include approved indications for Dupixent, such as atopic dermatitis, asthma, chronic rhinosinusitis with nasal polyposis (CRSwNP), prurigo nodularis and EoE. 

Dupixent has received regulatory approvals in one or more countries around the world for use in certain patients with atopic dermatitis, asthma, CRSwNP, EoE, and prurigo nodularis in different age populations. Dupixent is currently approved for one or more of these indications in more than 60 countries, including in Europe, the U.S. and Japan. More than 800,000 patients are being treated with Dupixent globally.

NOVARTIS LUTATHERA^® SIGNIFICANTLY REDUCED RISK OF DISEASE PROGRESSION OR DEATH BY 72% AS FIRST-LINE TREATMENT FOR PATIENTS WITH ADVANCED GASTROENTEROPANCREATIC NEUROENDOCRINE TUMORS

In the Phase III NETTER-2 trial, Lutathera plus octreotide LAR significantly extended median PFS to 22.8 months vs. 8.5 months with high-dose octreotide LAR in patients with newly diagnosed grade 2 and 3 advanced gastroenteropancreatic neuroendocrine tumors (GEP-NETs)¹

NETTER-2 is the first and only positive Phase III trial for a radioligand therapy (RLT) in the first-line setting, demonstrating the potential of RLTs in earlier lines

Novartis, a leader in radioligand therapy, is investigating a broad portfolio of RLTs in advanced cancers, in addition to GEP-NETs, including lung, prostate, breast, colon, glioblastoma and pancreatic cancers to continue reimagining medicine for patients

Basel, January 19, 2024 – Novartis presented data from the Phase III NETTER-2 trial showing that Lutathera^® (INN: lutetium (177Lu) oxodotreotide / USAN: lutetium Lu 177 dotatate) plus long-acting release (LAR) octreotide reduced the risk of disease progression or death by 72% as first-line therapy in patients with somatostatin receptor-positive (SSTR+) well-differentiated grade 2/3 advanced gastroenteropancreatic neuroendocrine tumors (GEP-NETs) versus high-dose octreotide LAR alone.¹ Data were presented at the 2024 American Society of Clinical Oncology (ASCO) Gastrointestinal (GI) Cancers Symposium.

“These positive results for Lutathera are practice-changing and offer new first-line treatment data for patients who have a significant unmet need. This study confirms the clinical benefit of first-line radioligand therapy for newly diagnosed patients living with these types of advanced GEP-NETs,” said Dr. Simron Singh, Associate Professor of Medicine at the University of Toronto and cofounder of the Susan Leslie Clinic for Neuroendocrine Tumours at the Odette Cancer Centre, Sunnybrook Health Sciences Centre, Ontario, Canada. “These findings should instill confidence among physicians in using Lutathera as a first-line treatment for patients with this life-threatening type of cancer.”

“This is the first positive Phase III trial of a radioligand therapy in the first-line setting, and the overall efficacy and safety results are amongst the most clinically relevant observed to date in this kind of advanced cancer, addressing a significant unmet need for patients with newly diagnosed advanced GEP-NETs,” said Jeff Legos, Global Head of Oncology Development at Novartis. “The positive results are a significant advancement and further reaffirm our strategy to research and develop radioligand therapies in earlier lines of treatment or stages of disease to improve outcomes for patients.”

No new or unexpected safety findings were observed in the study and data are consistent with the already well-established safety profile of Lutathera.¹ Most patients (88%) in the Lutathera arm received all four cycles of Lutathera treatment. The most common all-grade AEs (≥20%) for the Lutathera arm vs. control arm were nausea (27.2% vs 17.8%), diarrhea (25.9% vs 34.2%) and abdominal pain (17.7% vs 27.4%), and the most common grade ≥3 AE (>5%) was lymphocyte count decreased (5.4% vs 0%).

NETs are a type of cancer that originate in neuroendocrine cells throughout the body and are commonly considered slow-growing malignancies. However, some NETs are associated with rapid progression and poor prognosis and in many cases, diagnosis is delayed until patients have advanced disease.^2-4 Even though NETs are a rare (orphan) disease, their incidence has increased over the past several decades^2-5 and there is a need for continued research into treatment options for newly diagnosed patients.

The NETTER-2 trial is ongoing for further evaluation of secondary endpoints including overall survival and long-term safety.

About NETTER-2

NETTER-2 (NCT03972488) is an open-label, multi-center, randomized, comparator-controlled Phase III trial assessing whether Lutathera plus octreotide LAR when taken as a first-line treatment can prolong PFS in patients with high-proliferation rate tumors (G2 and G3), compared to treatment with high-dose (60 mg) long-acting octreotide.⁶ Eligible patients were diagnosed with SSTR-positive advanced GEP-NETs within 6 months before enrollment.⁶

About Lutathera^®

Lutathera^® (INN: lutetium (177Lu) oxodotreotide / USAN: lutetium Lu 177 dotatate) is approved in the US for the treatment of adult patients with SSTR-positive GEP-NETs, including those in the foregut, midgut and hindgut, an indication which includes the NETTER-2 population. Lutathera is also approved in Europe for unresectable or metastatic, progressive, well-differentiated (G1 and G2), SSTR-positive GEP-NETs in adults,^7,8 and in Japan for SSTR-positive NETs.

Novartis and Radioligand Therapy (RLT)

Novartis is reimagining cancer care with RLT for patients with advanced cancers. By harnessing the power of radioactive atoms and applying it to advanced cancers, RLT is theoretically able to deliver radiation to target cells anywhere in the body.^9,10

Novartis is investigating a broad portfolio of RLTs, exploring new isotopes, ligands and combination therapies to look beyond gastroenteropancreatic neuroendocrine tumors (GEP-NETs) and prostate cancer and into breast, colon, lung and pancreatic cancer.

With established global expertise, and specialized supply chain and manufacturing capabilities across the Novartis network, we are supporting growing demand for our RLT medicines. Our production capabilities continue to expand and now include sites in Millburn, US, Zaragoza, Spain, Ivrea, Italy and our new state-of-the-art facility in Indianapolis, US. We recently announced plans to expand our manufacturing capabilities and build additional points of supply in Sasayama, Japan, and Haiyan, Zhejiang, China, to produce RLTs for patients in Japan and China. We are continually evaluating additional opportunities to increase capacity around the world.

Disclaimer

This press release contains forward-looking statements within the meaning of the United States Private Securities Litigation Reform Act of 1995. Forward-looking statements can generally be identified by words such as “potential,” “can,” “will,” “plan,” “may,” “could,” “would,” “expect,” “anticipate,” “seek,” “look forward,” “believe,” “committed,” “investigational,” “pipeline,” “launch,” or similar terms, or by express or implied discussions regarding potential marketing approvals, new indications or labeling for the investigational or approved products described in this press release, or regarding potential future revenues from such products.. You should not place undue reliance on these statements. Such forward-looking statements are based on our current beliefs and expectations regarding future events and are subject to significant known and unknown risks and uncertainties. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those set forth in the forward-looking statements. There can be no guarantee that the investigational or approved products described in this press release will be submitted or approved for sale or for any additional indications or labeling in any market, or at any particular time. Nor can there be any guarantee that such products will be commercially successful in the future. In particular, our expectations regarding such products could be affected by, among other things, the uncertainties inherent in research and development, including clinical trial results and additional analysis of existing clinical data; regulatory actions or delays or government regulation generally; global trends toward health care cost containment, including government, payor and general public pricing and reimbursement pressures and requirements for increased pricing transparency; our ability to obtain or maintain proprietary intellectual property protection; the particular prescribing preferences of physicians and patients; general political, economic and business conditions, including the effects of and efforts to mitigate pandemic diseases; safety, quality, data integrity or manufacturing issues; potential or actual data security and data privacy breaches, or disruptions of our information technology systems, and other risks and factors referred to in Novartis AG’s current Form 20-F on file with the US Securities and Exchange Commission. Novartis is providing the information in this press release as of this date and does not undertake any obligation to update any forward-looking statements contained in this press release as a result of new information, future events or otherwise.

About Novartis

Novartis is an innovative medicines company. Every day, we work to reimagine medicine to improve and extend people’s lives so that patients, healthcare professionals and societies are empowered in the face of serious disease. Our medicines reach more than 250 million people worldwide.

Reimagine medicine with us:

Visit us at:

novartis.com

NEWS FROM THE AMERICAN
COLLEGE OF SURGEONS

Colorectal Cancer Awareness Month: What to Know about the Rise of Colorectal Cancer in Younger Adults

Experts with the American College of Surgeons share colorectal cancer prevention tips and insights into the concerning rise of diagnoses in younger adults

CHICAGO (March 5, 2024): Rates of colorectal cancer have been rising consistently in younger adults — a trend that concerns surgeons and other medical professionals at the forefront of treating the disease.

“We’ve been noticing an alarming rise in colorectal cancer in adults under the age of 50. In fact, people born in the 1990s are two times more likely than people born in the 1950s to develop colorectal cancer,” said James T. McCormick, DO, FACS, FASCRS, a colorectal surgeon and American College of Surgeons Commission on Cancer (CoC) State Chair of the Pennsylvania chapter. “And that’s remarkably striking. We’re not quite sure why that’s happening or how to screen for it at such a young age. That’s the conundrum.”

For Colorectal Cancer Awareness Month this March, experts with the American College of Surgeons are available for interviews to share insights about the rise of colorectal cancer in younger adults and what steps people of all ages can take to reduce their risk of dying from the disease.

How much is colorectal cancer
increasing in younger adults?

Researchers have noted a 15% increase in colon cancer diagnoses in people aged 18-50 since 2004, according to hospital-based data from the National Cancer Database (NCDB). By comparison, there was only a 3% increase in colon cancer diagnoses in adults aged 45-55 during the same period.

The NCDB, a clinical oncology database jointly operated by the CoC and the American Cancer Society, captures approximately 74% of all newly diagnosed cancers in the U.S.

Colorectal cancer is also killing more young adults. According to the American Cancer Society, colorectal cancer is now the leading cause of cancer deaths in men younger than 50 and the second leading cause of cancer deaths in women of the same age group.

Why is colorectal cancer increasing among young people?

The exact causes behind the increase of colorectal cancer in younger people are not fully understood. However, most experts believe that the rise results from multiple factors, including environmental changes, potential exposure to toxins, genetic factors that may increase a person’s risk of developing the disease earlier in life, and lifestyle factors such as high consumption of ultra-processed foods. Research into all these areas is ongoing.

 “We really don’t know one single cause, but it’s likely multifactorial, and risk factors may depend on where the patient lives, what they eat, their lifestyle habits, and other hereditary factors,” said Nitin Mishra, MBBS, MPH, FACS, CoC State Chair of the Arizona chapter, and an associate professor of surgery at Mayo Clinic in Phoenix, Arizona.

What can people do to prevent colorectal cancer?

Despite the unknown, there are several steps everyone can take to reduce their risk of developing the disease and/or dying from colorectal cancer.

First and foremost, ACS experts recommend that people of all ages remain vigilant and report any changes in bowel habits, including bleeding and persistent changes such as constipation or diarrhea, to their primary care physician. Be persistent, and don’t be afraid to ask questions.

“I think a lot of prevention starts with awareness,” said Paula Denoya, MD, FACS, FASCRS, CoC State Chair of the Eastern Long Island-NY chapter and a colorectal surgeon at the Stony Brook Cancer Center. “We’ve all seen patients who had rectal bleeding that was dismissed as hemorrhoids or IBS symptoms for a while before they were found to have colorectal cancer. Knowing your family history is also critically important.”

Starting at age 45, all people should be screened for colorectal cancer annually. Screening may need to start earlier for people with a family history of the disease or for people considered high-risk for 

the disease due to other health factors.

The gold standard of colorectal cancer screening is with a colonoscopy, which can help physicians detect colorectal cancer at its earliest stage, when it’s more treatable, and even prevent colorectal cancer through the detection and removal of precancerous growths called polyps. Screening with colonoscopy may be one factor of many that has resulted in nearly 16,000 fewer colon cancer diagnoses among older adults per year, according to hospital-based data from the NCDB. Still, approximately 1 in 4 adults of screening age are not up to date with colorectal cancer screening recommendations, according to national data estimates.

Finally, exercising regularly to maintain a healthy body weight and eating a balanced diet high in lean meat, fiber, whole grains, vegetables, and fruits may also help reduce risk.

“Staying active even has other health benefits besides reducing the risk of colorectal cancer,” said Howard Kaufman, MD, FACS, CoC State Chair of the Southern California chapter and regional medical director of Huntington Cancer Center, an affiliate of Cedars-Sinai Cancer, in Pasadena, California. “For colorectal cancer, my main takeaway message is to get screened if you’re at the appropriate age or have other risk factors, and to see your doctor if you have any unusual bowel symptoms. If your symptoms persist and there’s not a plan to evaluate those symptoms from your doctor, then seek additional care. Don’t ignore symptoms.”

Additional resources:

Colorectal Cancer: What to Know
(American College of Surgeons)

facs.org/colorectalcancer/

References

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