CAMBRIDGE, Mass.--(BUSINESS WIRE)--Ironwood Pharmaceuticals, Inc. (NASDAQ:IRWD) announced today that the United States Patent and Trademark Office (USPTO) has issued a Notice of Allowance for a patent application covering methods of using LINZESS® (linaclotide) to treat patients with irritable bowel syndrome with constipation (IBS-C) or chronic idiopathic constipation (CIC). The patent application, co-owned by Ironwood and Forest Laboratories, Inc., is expected to issue in mid-2014 and extend LINZESS patent protection into 2031.
The patent application specifically applies to LINZESS, which is the current U.S. commercial formulation of linaclotide. This formulation combines the active ingredient linaclotide with certain excipients, resulting in a product that is stable at room temperature for long periods and suitable for oral dosing, in a capsule that dissolves in the stomach and allows linaclotide to reach its target site of action along the surface of the intestinal epithelium. Creating a room temperature stable oral formulation for linaclotide, a fourteen amino acid peptide, was one of the most significant challenges Ironwood and Forest overcame in developing the molecule into a commercially-viable product. This patent would be a significant addition to the LINZESS patent portfolio, providing patent protection for LINZESS for several additional years.
LINZESS is approved and marketed in the United States for the treatment of adult patients suffering from IBS-C or CIC. It is the first and only guanylate cyclase-C (GC-C) agonist approved by the FDA. Composition of matter patents currently cover LINZESS to 2024, and a pending patent term extension would extend the composition of matter patent coverage to 2026. Ironwood and Forest also own pending patent applications covering the LINZESS commercial formulation, which are expected to provide further patent protection.
A notice of allowance is a written notification issued after the USPTO makes a determination that a patent can be granted from an application. The vast majority of patent applications that receive a notice of allowance will proceed to issue as a U.S. patent; however, a notice of allowance is not a guarantee of patent issuance.
About LINZESS (linaclotide)
LINZESS is the first and only guanylate cyclase-C (GC-C) agonist approved by the FDA for the treatment of both irritable bowel syndrome with constipation (IBS-C) and chronic idiopathic constipation (CIC) in adults. LINZESS is a once-daily capsule that helps relieve the abdominal pain and constipation associated with IBS-C, as well as the constipation, infrequent stools, hard stools and incomplete evacuation associated with CIC. The recommended dose is 290 mcg for IBS-C patients and 145 mcg for CIC patients. LINZESS should be taken at least 30 minutes before the first meal of the day.
LINZESS is thought to work in two ways based on nonclinical studies. LINZESS binds to the GC-C receptor locally, within the intestinal epithelium. Activation of GC-C results 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 placebo-controlled Phase III clinical trials of more than 2,800 adults, LINZESS was shown to reduce abdominal pain in IBS-C patients and increase bowel movement frequency in both IBS-C patients and CIC patients. Improvement in abdominal pain and constipation occurred in the first week of treatment and was maintained throughout the 12-week treatment period. Maximum effect on abdominal pain was seen at weeks 6-9 and maximum effect on constipation occurred during the first week. When a subset of LINZESS-treated patients in the trials were switched to placebo, they reported their symptoms returned toward pretreatment levels within one week, while placebo-treated patients switched to LINZESS reported symptom improvements. LINZESS is contraindicated in pediatric patients up to 6 years of age. The use of LINZESS in pediatric patients 6 through 17 years of age should be avoided. In nonclinical studies, administration of a single, clinically relevant adult oral dose of linaclotide caused deaths in young juvenile mice. LINZESS has not been studied in pediatric patients. In adults with IBS-C or CIC treated with LINZESS, the most commonly reported adverse event was diarrhea.
Ironwood and Forest Laboratories, Inc. are co-promoting LINZESS in the United States. Linaclotide is marketed by Almirall, S.A. for the treatment of adults with moderate to severe IBS-C in Europe under the brand name CONSTELLA®. Ironwood also has partnered with Astellas Pharma Inc. for development and commercialization of linaclotide in Japan and with AstraZeneca for development and commercialization in China.
About Ironwood Pharmaceuticals
Ironwood Pharmaceuticals (NASDAQ:IRWD) is focused on creating medicines that make a difference for patients, building value to earn the continued support of our fellow shareholders, and empowering our team to passionately pursue excellence. We discovered, developed and are commercializing linaclotide, which is approved in the United States and Europe. Our pipeline priorities include exploring further opportunities for linaclotide, as well as leveraging our therapeutic expertise in gastrointestinal disorders and our pharmacologic expertise in guanylate cyclases to address patient needs across the upper and lower gastrointestinal tract. Ironwood was founded in 1998 and is headquartered in Cambridge, Mass. Connect with us at www.ironwoodpharma.com or on Twitter at www.twitter.com/ironwoodpharma; information that may be important to investors will be routinely posted in both these locations.
LINZESS® and CONSTELLA® are trademarks owned by Ironwood Pharmaceuticals, Inc.
Important Safety Information
WARNING: PEDIATRIC RISK
LINZESS is contraindicated in pediatric patients up to 6 years of age. Use should be avoided in pediatric patients 6 through 17 years of age. In nonclinical studies, administration of a single, clinically relevant adult oral dose of linaclotide caused deaths in young juvenile mice.
- LINZESS is contraindicated in pediatric patients up to 6 years of age.
- LINZESS is contraindicated in patients with known or suspected mechanical gastrointestinal obstruction.
Warnings and Precautions
- LINZESS is contraindicated in pediatric patients up to 6 years of age. In nonclinical studies, deaths occurred within 24 hours in young juvenile mice (1 to 3 week-old mice; approximately equivalent to human pediatric patients less than 2 years of age) following administration of one or two daily oral doses of linaclotide.
- Use of LINZESS should be avoided in pediatric patients 6 through 17 years of age. Linaclotide did not cause deaths in older juvenile mice (approximately equivalent to humans age 12 to 17 years). Although there were no deaths in older juvenile mice, given the deaths in young juvenile mice and the lack of clinical safety and efficacy data in pediatric patients, use of LINZESS should be avoided in pediatric patients 6 through 17 years of age.
- Diarrhea was the most common adverse reaction of LINZESS-treated patients in the pooled IBS-C and CIC double-blind placebo-controlled trials. Severe diarrhea was reported in 2% of LINZESS-treated patients. The incidence of diarrhea was similar in the IBS-C and CIC populations.
- Patients should be instructed to stop LINZESS if severe diarrhea occurs and to contact their healthcare provider, who should consider dose suspension.
- In IBS-C clinical trials, the most common adverse reactions in LINZESS-treated patients (incidence ≥2% and greater than placebo) were 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 clinical trials, the most common adverse reactions in LINZESS-treated patients (incidence ≥2% and greater than placebo) were 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%).
Please see full Prescribing Information including Boxed Warning: http://www.frx.com/pi/linzess_pi.pdf
This press release contains forward-looking statements. Investors are cautioned not to place undue reliance on these forward-looking statements, including, but not limited to, statements about the expected issuance of the methods of use patent for which the USPTO issued a notice of allowance; the expected period of patent protection associated with the patent, if it’s issued; the stability of LINZESS® in its room temperature formulation; the potential patent term extension for the linaclotide composition of matter patent; and the anticipated patent protection associated with other pending patent applications. 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 statement. Applicable risks and uncertainties include, but are not limited to, the risk that the USPTO does not issue the methods of use patent, or any other patents for which there is an outstanding patent application, in the timeline expected or at all; the methods of use patent, or any other patent, is challenged or invalidated, in whole or in part; any of our patents are deemed to infringe on the intellectual property rights of other products or product candidates; other manufacturers are able to create another room temperature stable formulation of linaclotide that is not covered by this or any of our other patents or patent applications; and LINZESS® is not room temperature stable in its current formulation, or any formulation, as long as expected. Applicable risks also include those that are listed under the heading "Risk Factors" and elsewhere in Ironwood's Annual Report on Form 10‐K for 2013, in addition to the risk factors that are listed from time to time in Ironwood's Annual Reports on Form 10‐K, Quarterly Reports on Form 10‐Q and any subsequent SEC filings. Ironwood undertakes no obligation to update these forward-looking statements to reflect events or circumstances occurring after this press release. Except as otherwise noted, these forward-looking statements speak only as of the date of this press release. All forward‐looking statements are qualified in their entirety by this cautionary statement.