Ironwood Pharmaceuticals Announces FDA Approval of Revised LINZESS® (linaclotide) Label

Rhea-AI Summary

Ironwood Pharmaceuticals (NASDAQ: IRWD) announced FDA approval for a revised label of LINZESS (linaclotide) based on pediatric clinical safety data. The update narrows the boxed warning for dehydration risks to children under two years, previously applicable to all under 18. The labeling reflects ongoing studies to enhance safety profiles for pediatric use. LINZESS remains contraindicated for children under two, and its effectiveness for patients under 18 is not yet established. The drug is indicated for adults with irritable bowel syndrome with constipation (IBS-C) and chronic idiopathic constipation (CIC).

Positive

• FDA approval for revised LINZESS label enhances market potential.
• Focus on pediatric safety might expand LINZESS usage in younger demographics.
• LINZESS remains the leading prescription for IBS-C and CIC in adults.

Negative

• LINZESS safety and efficacy in pediatric patients under 18 remain unproven.
• The boxed warning for dehydration risk persists for children under two.

BOSTON--(BUSINESS WIRE)--

Ironwood Pharmaceuticals, Inc. (NASDAQ: IRWD), a GI-focused healthcare company, today announced that the U.S. Food and Drug Administration (FDA) approved a revised label for LINZESS^® (linaclotide) based on clinical safety data that has been generated thus far in pediatric studies. The updated label modifies the boxed warning for risk of serious dehydration and contraindication against use in children to those less than two years of age. The boxed warning and contraindication previously applied to all children less than 18 years of age and less than 6 years of age, respectively. The safety and effectiveness of LINZESS in patients less than 18 years of age have not been established. LINZESS is indicated in adults for the treatment of irritable bowel syndrome with constipation (IBS-C) and chronic idiopathic constipation (CIC).

“The warning on the LINZESS label at launch was primarily applied due to preclinical findings, and there was an absence of any clinical data in pediatric populations at the time,” said Michael Shetzline, M.D., Ph. D, chief medical officer, senior vice president and head of drug development at Ironwood. “Since approval, we have worked diligently on generating clinical data to better characterize the safety profile for pediatric populations. This label update reflects a significant milestone, and we look forward to continuing to investigate the safety and efficacy of LINZESS for children.”

The LINZESS prescribing information continues to include a boxed warning for children less than 2 years of age and a contraindication against use in this population. Further clinical data are also required to establish the safety and efficacy of LINZESS in the pediatric population (less than 18 years of age). Diarrhea, including severe diarrhea, is a potentially serious side effect of LINZESS.

The approved revision to the boxed warning and the safety information of LINZESS in children is based on pediatric clinical safety data, including:

• Clinical studies that enrolled patients with functional constipation (FC) and those with irritable bowel syndrome with constipation (IBS-C); as well as clinical study data in children with FC
• Data from a human guanylate-cyclase (GC-C) expression study in pediatric subjects. LINZESS is a GC-C agonist
• Post-marketing data from the LINZESS global safety database in children who took LINZESS
• An analysis of the IBM^® MarketScan^® Database assessing the use of LINZESS in pediatric patients from the United States and
• Safety and efficacy results from a retrospective review of children at the Nationwide Children’s Hospital in Columbus, Ohio¹ with FC or IBS-C who had taken LINZESS.

About LINZESS (linaclotide)

LINZESS^® is the #1 prescribed brand in the U.S. for the treatment of adult patients with irritable bowel syndrome with constipation (IBS-C) or chronic idiopathic constipation (CIC), based on IQVIA data.

LINZESS is a once-daily capsule that helps relieve the abdominal pain, constipation and overall abdominal symptoms of bloating, discomfort and pain associated with IBS-C, as well as the constipation, infrequent stools, hard stools, straining and incomplete evacuation associated with CIC. The recommended dose is 290 mcg for IBS-C patients and 145 mcg for CIC patients, with a 72-mcg dose approved for use in CIC depending on individual patient presentation or tolerability. LINZESS should be taken at least 30 minutes before the first meal of the day.

LINZESS is contraindicated in pediatric patients less than 2 years of age. In neonatal mice, linaclotide increased fluid secretion as a consequence of age-dependent elevated guanylate cyclase-C (GC-C) agonism which was associated with increased mortality within the first 24 hours due to dehydration. There was no age-dependent trend in GC-C intestinal expression in a clinical study of children 2 to less than 18 years of age; however, there are insufficient data available on GC-C intestinal expression in children less than 2 years of age to assess the risk of developing diarrhea and its potentially serious consequences in these patients. The safety and effectiveness of LINZESS in pediatric patients less than 18 years of age have not been established. In adults with IBS-C or CIC treated with LINZESS, the most commonly reported adverse event was diarrhea.

LINZESS is not a laxative; it is the first medicine approved by the FDA in a class called GC-C agonists. LINZESS contains a peptide called linaclotide that activates the GC-C receptor in the intestine. Activation of GC-C is thought to result in increased intestinal fluid secretion and accelerated transit and a decrease in the activity of pain-sensing nerves in the intestine. The clinical relevance of the effect on pain fibers, which is based on nonclinical studies, has not been established.

In the United States, Ironwood and AbbVie co-develop and co-commercialize LINZESS for the treatment of adults with IBS-C or CIC. In Europe, AbbVie markets linaclotide under the brand name CONSTELLA^® for the treatment of adults with moderate to severe IBS-C. In Japan, Ironwood's partner Astellas markets linaclotide under the brand name LINZESS for the treatment of adults with IBS-C or CIC. Ironwood also has partnered with AstraZeneca for development and commercialization of LINZESS in China, and with AbbVie for development and commercialization of linaclotide in all other territories worldwide.

LINZESS Important Safety Information

INDICATIONS AND USAGE
LINZESS is indicated in adults for the treatment of:

• irritable bowel syndrome with constipation (IBS-C)
• chronic idiopathic constipation (CIC)

IMPORTANT SAFETY INFORMATION

WARNING: RISK OF SERIOUS DEHYDRATION IN PEDIATRIC PATIENTS LESS THAN 2 YEARS OF AGE   LINZESS is contraindicated in patients less than 2 years of age. In nonclinical studies in neonatal mice, administration of a single, clinically relevant adult oral dose of linaclotide caused deaths due to dehydration.

Contraindications

• LINZESS is contraindicated in patients less than 2 years of age due to the risk of serious dehydration.
• LINZESS is contraindicated in patients with known or suspected mechanical gastrointestinal obstruction.

Warnings and Precautions
Risk of Serious Dehydration in Pediatric Patients Less Than 2 Years of Age

• LINZESS is contraindicated in patients less than 2 years of age. In neonatal mice, linaclotide increased fluid secretion as a consequence of age-dependent elevated GC-C agonism which was associated with increased mortality within the first 24 hours due to dehydration. There was no age-dependent trend in GC-C intestinal expression in a clinical study of children 2 to less than 18 years of age; however, there are insufficient data available on GC-C intestinal expression in children less than 2 years of age to assess the risk of developing diarrhea and its potentially serious consequences in these patients. The safety and effectiveness of LINZESS in patients less than 18 years of age have not been established.

Diarrhea

• Diarrhea was the most common adverse reaction in LINZESS-treated patients in the pooled IBS-C and CIC double-blind placebo-controlled trials. The incidence of diarrhea was similar in the IBS-C and CIC populations. Severe diarrhea was reported in 2% of 145 mcg and 290 mcg LINZESS-treated patients, and in <1% of 72 mcg LINZESS-treated CIC patients. If severe diarrhea occurs, dosing should be suspended and the patient rehydrated.

Common Adverse Reactions (incidence ≥2% and greater than placebo)

• In IBS-C clinical trials: diarrhea (20% vs 3% placebo), abdominal pain (7% vs 5%), flatulence (4% vs 2%), headache (4% vs 3%), viral gastroenteritis (3% vs 1%) and abdominal distension (2% vs 1%).
• In CIC trials of a 145 mcg dose: diarrhea (16% vs 5% placebo), abdominal pain (7% vs 6%), flatulence (6% vs 5%), upper respiratory tract infection (5% vs 4%), sinusitis (3% vs 2%) and abdominal distension (3% vs 2%). In a CIC trial of a 72 mcg dose: diarrhea (19% vs 7% placebo) and abdominal distension (2% vs <1%).

Please see full Prescribing Information including Boxed Warning: http://www.allergan.com/assets/pdf/linzess_pi

About Ironwood Pharmaceuticals

Ironwood Pharmaceuticals (Nasdaq: IRWD) is a leading gastrointestinal (GI) healthcare company on a mission to advance the treatment of GI diseases and redefine the standard of care for GI patients. We are pioneers in the development of LINZESS^® (linaclotide), the U.S. branded prescription market leader for adults with irritable bowel syndrome with constipation (IBS-C) or chronic idiopathic constipation (CIC). Under the guidance of our seasoned industry leaders, we continue to build upon our history of GI innovation and challenge what has been done before to shape what the future holds. We keep patients at the heart of our R&D and commercialization efforts to reduce the burden of GI diseases and address significant unmet needs.

Founded in 1998, Ironwood Pharmaceuticals is headquartered in Boston, Massachusetts.

We routinely post information that may be important to investors on our website at www.ironwoodpharma.com. In addition, follow us on Twitter and on LinkedIn.

Forward-Looking Statements

This press release contains forward-looking statements. Investors are cautioned not to place undue reliance on these forward-looking statements, including the status of our development program to investigate the safety and efficacy of LINZESS for children. These forward-looking statements speak only as of the date of this press release, and Ironwood undertakes no obligation to update these forward-looking statements. Each forward-looking statement is subject to risks and uncertainties that could cause actual results to differ materially from those expressed or implied in such a statement. Applicable risks and uncertainties include those related to the effectiveness of development and commercialization efforts by us and our partners; preclinical and clinical development, manufacturing and formulation development of linaclotide; the risk that clinical programs and studies may not progress or develop as anticipated, including that studies are delayed or discontinued for any reason, such as safety, tolerability, enrollment, manufacturing, economic or other reasons; the risk that findings from our completed nonclinical and clinical studies may not be replicated in later studies; the risk that we or our partners are unable to obtain, maintain or manufacture sufficient LINZESS or our product candidates, or otherwise experience difficulties with respect to supply or manufacturing; the efficacy, safety and tolerability of linaclotide and our product candidates; the risk that the therapeutic opportunities for LINZESS or our product candidates are not as we expect; decisions by regulatory and judicial authorities; the risk we may never get additional patent protection for linaclotide and other product candidates; the risk that we may never get sufficient patent protection for linaclotide and other product candidates, that patents for linaclotide or other products may not provide adequate protection from competition, or that we are not able to successfully protect such patents; outcomes in legal proceedings to protect or enforce the patents relating to our products and product candidates, including abbreviated new drug application litigation; developments in the intellectual property landscape; challenges from and rights of competitors or potential competitors; the risk that our planned investments do not have the anticipated effect on our company revenues; the risk that we are unable to manage our expenses or cash use, or are unable to commercialize our products as expected; the impact of the COVID-19 pandemic; and the risks listed under the heading "Risk Factors" and elsewhere in Ironwood's Quarterly Report on Form 10-Q for the quarter ended June 30, 2021, and in our subsequent SEC filings.

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1		Paediatr Drugs. 2021; 23(3): 307–314

 

View source version on businesswire.com: https://www.businesswire.com/news/home/20210826005210/en/

Media:

Beth Calitri, 978-417-2031

bcalitri@ironwoodpharma.com

Investors:

Matt Roache, 617-621-8395

mroache@ironwoodpharma.com

Source: Ironwood Pharmaceuticals, Inc.

FAQ

What is the updated FDA label for LINZESS (IRWD)?

The FDA updated LINZESS's label to restrict the dehydration risk warning to children under two years, rather than under 18.

What are the indications for LINZESS?

LINZESS is indicated for adults with irritable bowel syndrome with constipation (IBS-C) and chronic idiopathic constipation (CIC).

What safety concerns are associated with LINZESS in pediatric patients?

LINZESS is contraindicated for children under two due to serious dehydration risks, and its safety in those under 18 is not established.

How does the revised label affect LINZESS's market potential?

The revision may broaden LINZESS's market by potentially allowing its use in a wider pediatric population in the future.

What common side effects are reported with LINZESS?

The most frequently reported adverse event is diarrhea, affecting a significant percentage of patients treated with LINZESS.