- U.S. LINZESS® (linaclotide) quarterly total prescription growth of approximately 12% versus prior quarter and approximately 108% versus prior year -
- LINZESS net sales of
- Achieved profitability for U.S. LINZESS collaboration in fourth quarter -
- Nine clinical studies and up to four data readouts expected in 2015 -
"We made great strides in 2014 delivering on our strategy. We continue
to maximize LINZESS, with quarterly total prescription growth of
approximately 108% year over year. The U.S. collaboration also was
profitable for the fourth quarter - an important inflection point toward
substantial operating leverage and cash flows into at least 2031," said
Fourth Quarter 2014 and Recent Highlights
LINZESS U.S. net sales, as provided by Actavis plc, were
$93.8 millionin the fourth quarter of 2014, an increase of approximately 18% quarter over quarter.
- Gross-to-net adjustments for the fourth quarter were in the mid-30s percent as compared to approximately 30% in the third quarter of 2014.
- Wholesaler inventory levels were higher at the end of the fourth quarter compared with the third quarter, but were within the expected two to three week range.
January 5, 2015, Ironwood and Actavis increased the wholesale acquisition cost of LINZESS by approximately 9.5% to its current price of $9.24per capsule.
Net profit for the LINZESS U.S. collaboration with Actavis, including
commercial costs and expenses and research & development (R&D)
$18.2 millionin the fourth quarter of 2014. LINZESS U.S. net profit is shared equally with Actavis under the terms of the collaboration.
Greater than 440,000 total LINZESS prescriptions were filled in the
fourth quarter of 2014, an increase of approximately 12% quarter over
quarter, and over two million LINZESS prescriptions have been filled
since the product's launch in
December 2012, according to IMS Health.1
- More than 110,000 healthcare practitioners have prescribed LINZESS to more than 530,000 unique patients since the product's launch, according to IMS Health.
More than 70% of people with commercial insurance or
Medicare Part Dplans had unrestricted access to LINZESS as of December 2014. Additionally, as of December 2014, approximately 75% of people with commercial insurance had access to LINZESS for a co-pay of $30or less through formulary coverage or the LINZESS Instant Savings Program.
1 IMS Health restated its historical weekly prescription data
Research & Development
Ironwood and Actavis continue to evaluate opportunities to strengthen
linaclotide's clinical utility in its indicated patient population, as
well as to develop and seek approval of linaclotide in additional
approved indications, patient populations and formulations.
Development highlights during the fourth quarter and recent period
- Initiated enrollment in a randomized, double-blind, placebo-controlled Phase III clinical trial of a once-daily 72 mcg dose of linaclotide in adult patients with chronic idiopathic constipation (CIC). If approved, the 72 mcg dose and the currently approved 145 mcg dose would provide a broader range of treatment options to physicians and the up to 35 million adult patients in the U.S. suffering from CIC, further accelerating the expansion of LINZESS use within this indication. Data from this trial are expected in 2016.
- Initiated enrollment in a randomized, double-blind, placebo-controlled Phase II clinical trial evaluating linaclotide for the treatment of adults suffering from opioid-induced constipation. Data from this trial are expected in the second half of 2015.
Ironwood continued to leverage its gastrointestinal (GI) and guanylate
cyclase expertise to advance a pipeline of product candidates designed
to address unmet needs across the upper and lower GI tract, as well as
investigate multiple therapeutic opportunities within its soluble
guanylate cyclase (sGC) program. Development highlights during the
fourth quarter and recent period include:
- Reported positive top-line data from an exploratory Phase IIa clinical study evaluating IW-3718, Ironwood's investigational gastric retentive bile acid sequestrant. Data from this study demonstrated encouraging improvements in relief of heartburn and certain other symptoms often associated with refractory gastroesophageal reflux disease (GERD), such as regurgitation, epigastric burning, early fullness and post-prandial fullness. Based on these initial data, Ironwood intends to advance IW-3718 into a dose-ranging Phase IIb study seeking to amplify symptom relief by optimizing the dose and formulation.
- Initiated a randomized, double-blind, placebo-controlled, multi-site Phase IIa clinical study evaluating the ability of IW-9179 to provide relief of diabetic gastroparesis symptoms. IW-9179 is a guanylate cyclase-C (GC-C) agonist designed to target the upper GI tract. Data from this trial are expected in the first half of 2016.
- Initiated a Phase I clinical study with IW-1973, the company's first sGC candidate, with patient enrollment expected to begin in the coming weeks. Ironwood expects data from this study in the second half of 2015. In addition, the company expects to initiate a Phase I clinical trial with its second sGC candidate, IW-1701, in the second half of 2015. Both IW-1973 and IW-1701 are being explored for the potential treatment of cardiovascular diseases.
Global Partnerships for Linaclotide
Astellas Pharma Inc. began enrolling patients in its double-blind,
randomized, placebo-controlled Phase III clinical trial of linaclotide
in adult patients with irritable bowel syndrome with constipation
Japan. Astellas expects to complete the Phase III trial in 2016. Ironwood earned a $15 milliondevelopment milestone payment in the fourth quarter upon enrollment of the first patient in this trial.
Ironwoodand AstraZeneca AB completed enrollment in a Phase III clinical trial of linaclotide in adults with IBS-C for China. Data from this trial are expected in the second half of 2015.
Almirall, S.A. continues to commercialize CONSTELLA® (linaclotide) in
Europe, where it is approved for adult patients with moderate to severe IBS-C and is available in 10 European countries, including the United Kingdom, Italyand Spain.
Corporate and Financials
Collaborative Arrangements Revenue. Collaborative arrangements
revenue was approximately
$38.1 millionin the fourth quarter of 2014 compared with approximately $16.9 millionin the third quarter of 2014. Revenue consisted of approximately $23.9 millionin revenue associated with Ironwood's share of the net profits and losses from the sales of LINZESS in the U.S., approximately $10.2 millionof the $15.0 millionmilestone payment recognized during the fourth quarter from Astellas upon initiation of a Phase III IBS-C study for linaclotide in Japan, as well as approximately $4.0 millionin sales of linaclotide active pharmaceutical ingredient (API), amortization of deferred revenue associated with consideration received from Ironwood's collaboration with Astellas, revenue recognized in connection with the collaboration with AstraZeneca, and royalty payments based on sales of linaclotide in other territories outside of the U.S.
For the full year 2014, collaborative arrangements revenue was approximately
$76.4 million. This consisted of approximately $47.6 millionin revenue associated with Ironwood's share of the net profits and losses from the sales of LINZESS in the U.S., approximately $16.7 millionin sales of API, amortization of deferred revenue associated with consideration received from Ironwood's collaboration with Astellas, revenue recognized in connection with the collaboration with AstraZeneca, and royalty payments based on sales of linaclotide in other territories outside of the U.S., approximately $10.2 millionof the $15.0 milliondevelopment milestone payment from Astellas recognized during the fourth quarter, as well as approximately $1.9 millionin milestone payments from Almirall as a result of the commercial launches of CONSTELLAin Italyand Spain.
Cost of revenue. Cost of revenue is recognized upon shipment of
linaclotide API to certain licensing partners outside of the U.S.
Actavis records costs associated with linaclotide API in the U.S. In
the fourth quarter of 2014, cost of revenue was approximately $13.1
million, as compared to none in the third quarter of 2014. The
increase in cost of revenue was primarily due to an
$11.4 millionwrite-down of linaclotide API to an estimated net realizable value of $5 million, mainly due to a challenging commercial environment throughout Europe.
Operating Expenses. Operating expenses were approximately
$58.1 millionin the fourth quarter of 2014, as compared to approximately $53.6 millionin the third quarter of 2014. Operating expenses consisted of approximately $27.5 millionin R&D expenses, which included approximately $2.4 millionin non-cash share-based compensation expense, and approximately $30.6 millionin selling, general and administrative (SG&A) expenses, which included approximately $6.2 millionin non-cash share-based compensation expense.
For 2014, operating expenses were approximately $220.2 million and consisted of approximately
$101.9million in R&D expenses, which included approximately $9.5 million in non-cash share-based compensation expense, and approximately $118.3million in SG&A expenses, which included approximately $16.7million in non-cash share-based compensation expense.
Interest Expense. Interest expense was approximately
$5.3 millionand approximately $21.2 millionin the fourth quarter and full year 2014, respectively, in connection with the $175 milliondebt financing executed in January 2013.
Net Loss. Net loss was approximately
$37.6 million, or $0.27per share, in the fourth quarter of 2014, as compared to approximately $42.0 million, or $0.30per share, in the third quarter of 2014. For 2014, net loss was approximately $189.6 million, or $1.39per share.
Cash Position. Ironwood ended 2014 with approximately
$248 millionof cash, cash equivalents and available-for-sale securities. Ironwood used approximately $23 millionof cash for operations during the fourth quarter of 2014, as compared to approximately $39 millionin the third quarter of 2014.
2014 Financial Guidance.
Total operating expenses in 2014 were approximately
$220.2 million, consisting of approximately $101.9 millionin R&D expenses and approximately $118.3 millionin SG&A expenses.
Ironwood provided financial guidance for 2014 total operating
expenses to be in the range of
$215 millionto $245 million. This included $105 millionto $120 millionin R&D expenses and $110 millionto $125 millionin SG&A expenses.
- Ironwood provided financial guidance for 2014 total operating expenses to be in the range of
Non-linaclotide R&D expenses in 2014 represented approximately 53%
of total R&D expenses.
- Ironwood provided financial guidance for non-linaclotide R&D expenses in 2014 to be approximately 45% of total R&D expenses.
Total 2014 marketing and sales expenses for LINZESS were
Ironwood provided financial guidance for its combined Actavis
and Ironwood total 2014 marketing and sales expenses for
LINZESS to be in the range of
$240 millionto $270 million.
- Ironwood provided financial guidance for its combined Actavis and Ironwood total 2014 marketing and sales expenses for LINZESS to be in the range of
- Total operating expenses in 2014 were approximately
2015 Financial Guidance.
Ironwood expects its 2015 total operating expenses to be in the
$220 millionto $250 million, which includes $105 millionto $120 millionin R&D expenses and $115 millionto $130 millionin SG&A expenses.
Ironwood expects combined Actavis and Ironwood total 2015
marketing and sales expenses for LINZESS to be in the range of
$230 millionto $260 million.
- Ironwood expects its 2015 total operating expenses to be in the range of
Conference Call Information
Ironwood will host a conference call and webcast at
About LINZESS (linaclotide)
LINZESS® is the first and only guanylate cyclase-C (GC-C) agonist
approved by the
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 under 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 due to dehydration in young juvenile mice. The safety and efficacy of LINZESS in pediatric patients under 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.
Linaclotide is a guanylate cyclase-C receptor agonist (GCCA) with visceral analgesic and secretory activities. Linaclotide is a 14-amino acid synthetic peptide structurally related to the endogenous guanylin peptide family. Both linaclotide and its active metabolite bind to the guanylate cyclase-C receptor, on the luminal surface of the intestinal epithelium. Through its action at GC-C, linaclotide has been shown to reduce visceral pain and increase GI transit in animal models and increase colonic transit in humans. Activation of GC-C results in an increase in concentrations of cyclic guanosine monophosphate (cGMP), both extracellularly and intracellularly. Extracellular cGMP decreases pain-fiber activity, resulting in reduced visceral pain in animal models. Intracellular cGMP causes secretion of chloride and bicarbonate into the intestinal lumen, through activation of the cystic fibrosis transmembrane conductance regulator (CFTR), which results in increased intestinal fluid and accelerated transit.
Linaclotide was discovered by scientists at Ironwood and is marketed by
Almirall, S.A. for the treatment of adults with moderate to severe IBS-C
LINZESS® and CONSTELLA® are trademarks owned by
Important Safety Information
WARNING: PEDIATRIC RISK
LINZESS is contraindicated in pediatric patients under 6 years of age. In nonclinical studies, administration of a single, clinically relevant adult oral dose of linaclotide caused deaths due to dehydration in young juvenile mice. Use of LINZESS should be avoided in pediatric patients 6 through 17 years of age. The safety and efficacy of LINZESS has not been established in pediatric patients under 18 years of age.
- LINZESS is contraindicated in pediatric patients under 6 years of age.
- LINZESS is contraindicated in patients with known or suspected mechanical gastrointestinal obstruction.
Warnings and Precautions
- LINZESS is contraindicated in children under 6 years of age. The safety and effectiveness of LINZESS in pediatric patients under 18 years of age have not been established. In neonatal mice, increased fluid secretion as a consequence of GC-C agonism resulted in mortality within the first 24 hours due to dehydration. Due to increased intestinal expression of GC-C, children under 6 years of age may be more likely than older children and adults to develop significant diarrhea and its potentially serious consequences.
- Use of LINZESS should be avoided in pediatric patients 6 through 17 years of age. 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. The healthcare provider should consider dose suspension and rehydration.
- 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 development,
launch and commercialization plans for linaclotide and our product
candidates; commercial efforts for linaclotide and the drivers, timing,
impact and results thereof, including our LINZESS patient awareness
campaign; market size, growth and opportunity, and potential demand for
linaclotide and our product candidates, as well as their potential
impact on applicable markets; the potential indications for, and
benefits of, linaclotide and our product candidates; the anticipated
timing of pre-clinical and clinical developments; the design, timing and
results of clinical and pre-clinical trials; our top-line assessment of
the data from the Phase IIa clinical trial of IW-3718 in refractory GERD
and our ability to optimize the dose and commercial formation for
IW-3718; the expected period of patent exclusivity; the strength of the
intellectual property protection for our product and product candidates;
LINZESS profitability; inventory levels, write-downs and the drivers
thereof; and our company's financial performance and results, and
guidance and expectations related thereto, including our projected 2015
operating expenses (including certain research and development expenses
and selling, general and administrative expenses), cash flows, revenue
growth, operating leverage, cash burn, and 2015 marketing and sales
expense for LINZESS. 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, those related to
pre-clinical and clinical development, manufacturing, and formulation
development; the risk that findings from our completed nonclinical and
clinical studies may not be replicated in later trials; decisions made
by regulatory authorities; decisions made by the U.S. Patent and
Trademark Office and its foreign counterparts; intellectual property
rights of competitors or potential competitors; efficacy, safety and
tolerability of linaclotide and our product candidates; competition in
disease states; the commercial potential of linaclotide and our product
candidates; the risk that we may never get sufficient patent protection
for linaclotide and our product candidates; the risk that our planned
investments do not have the anticipated effect on our company revenues,
linaclotide or our product candidates; the risk that we are unable to
manage our operating expenses over the year due to foreseeable or
unforeseeable events or occurrences; the risk that we and our partner,
Actavis plc, are unable to commercialize LINZESS within the guided range
of expenses; and the risks presented by future business decisions made
by us, our partners and our competitors or potential competitors.
Applicable risks also include those that are listed under the heading
"Risk Factors" and elsewhere in Ironwood's Quarterly Report on Form 10-Q
for the quarter ended
Condensed Consolidated Balance Sheets
|Cash, cash equivalents and available-for-sale securities||$||248,334||$||197,602|
|Accounts receivable, net||25,839||3,213|
|Prepaid expenses and other current assets||10,603||6,168|
|Total current assets||289,730||229,128|
|Property and equipment, net||29,826||37,376|
|Liabilities and Stockholders' Equity|
|Accounts payable and accrued expenses||$||35,948||$||32,037|
|Current portion of capital lease obligations||1,152||1,139|
|Current portion of deferred rent||4,992||2,790|
|Current portion of deferred revenue||7,191||5,074|
|Current portion of long-term debt||11,258||—|
|Total current liabilities||60,541||41,040|
|Capital lease obligations||2,571||3,134|
|Total stockholders' equity||88,552||38,225|
|Total liabilities and stockholders' equity||$||333,513||$||278,962|
Condensed Consolidated Statements of Operations
(In thousands, except per share amounts)
Three Months Ended
|Collaborative Arrangements Revenue||$||38,073||$||5,031||$||76,436||$||22,881|
|Cost and expenses:|
|Cost of revenue||13,141||533||25,583||7,203|
|Research and development (1)||27,482||22,516||101,890||102,378|
|Selling, general and administrative (1)||30,575||28,720||118,333||123,228|
|Total cost and expenses||71,198||51,769||245,806||274,883|
|Loss from operations||(33,125||)||(46,738||)||(169,370||)||(252,002||)|
|Net loss per share—basic and diluted||$||(0.27||)||$||(0.43||)||$||(1.39||)||$||(2.35||)|
Weighted average number of common shares used in net loss per
(1) Non-cash compensation expenses reflected in the condensed
|Research and development||$||2,370||$||1,904||$||9,482||$||9,178|
|Selling, general and administrative||$||6,192||$||2,634||$||16,702||$||10,651|
LINZESS U.S. Collaboration Revenue/Expense Calculation1
Three Months Ended
|LINZESS U.S. net sales||$||93,752||$||51,044||$||296,980||$||118,753|
Commercial costs and expenses2
|Net profit (loss) on sales of LINZESS||$||33,702||$||(11,762||)||$||28,566||$||(145,998||)|
|Ironwood's share of net profit (loss)||$||16,851||$||(5,881||)||$||14,283||$||(72,999||)|
Ironwood's selling, general and administrative expenses3
|Profit share adjustment4||$||(623||)||$||—||$||1,689||$||—|
|Ironwood's collaborative arrangement revenue (expense)||$||23,882||$||2,914||$||47,618||$||(39,160||)|
1 Ironwood collaborates with Actavis on the development and
commercialization of linaclotide in
2 Includes cost of goods sold incurred by Actavis as well as selling, general and administrative expenses incurred by Actavis and Ironwood that are attributable to the cost-sharing arrangement between the parties.
3 Includes Ironwood's selling, general and administrative expenses attributable to the cost-sharing arrangement with Actavis.
4 Ironwood or Actavis may incur additional expenses related to certain contractual obligations, resulting in an adjustment to the company's share of the net profits as stipulated by the collaboration agreement.
Director, Corporate Communications
Director, Investor Relations
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