Ironwood's Linzess Beats PDUFA Date to Approval in IBS
By Marie Powers
Ironwood Pharmaceuticals Inc. crossed the commercial threshold Thursday morning, gaining FDA approval of irritable bowel syndrome (IBS) drug linaclotide more than a week ahead of the drug's Sept. 9 PDUFA date.
The company plans to launch the drug, branded Linzess, in the fourth quarter with partner Forest Laboratories Inc., of New York.
Trading in Cambridge, Mass.-based Ironwood's stock (NASDAQ:IRWD) was halted prior to the FDA's announcement. When trading resumed in mid-afternoon, shares edged lower, closing at $12.42 in what Jefferies & Co. Inc. analyst Corey Davis called a "muted reaction" to the FDA's expected decision.
Linaclotide, a first-in-class guanylate cyclase-C (GC-C) agonist that acts locally in the intestine with minimal systemic exposure, was cleared for use in the dual indications of chronic idiopathic constipation and IBS with constipation (IBS-C) in adults.
"We developed the drug in the two indications in parallel and submitted a single [new drug application], which is pretty unusual," Ironwood CEO Peter Hecht told BioWorld Today. "We're very pleased to have the breadth of that label."
Approval was based on data from four studies two in IBS-C, where 1,604 patients were randomized to 290 mcg of linaclotide or placebo for at least 12 weeks, and two in chronic constipation, where 1,272 patients were randomized to linaclotide at 145 mcg or 290 mcg or placebo for 12 weeks. The FDA approved the 145-mcg dose in chronic constipation since studies suggested it was just as effective as the higher dose.
Ironwood and Forest inked their potential $330 million deal on linaclotide in 2007, when Ironwood was known as Microbia Inc. The firms split U.S. development costs and profits, and Ironwood stands to receive royalties from sales in Mexico and Canada, where Forest holds exclusive rights to the compound. Ironwood also is set to bank an $85 million milestone payment linked to approval. (See BioWorld Today, Sept. 18, 2007.)
In a research note, Davis called linaclotide "one of the most significant assets in Forest's portfolio," with huge potential and strategic value for primary care physicians, patients and payers. Although the companies suggested a pricing range of $6 to $7 per day for both doses, Davis predicted the drug would price near the IBS-constipation drug Amitiza (lubiprostone, Sucampo Pharmaceuticals Inc./Abbott), around $7 per day.
In Europe, where linaclotide is under review, Ironwood is partnered with Almirall SA, of Barcelona, Spain, in a potential $95 million deal that included $40 million in up-front cash and a near-term equity milestone of $15 million. Ironwood could earn up to an additional $40 million in milestone payments, plus escalating royalties on product sales. (See BioWorld Today, May 5, 2009.)
In addition, Ironwood received $75 million in up-front and precommercial milestones on linaclotide, plus escalating royalties, in a deal with Tokyo's Astellas Pharma Inc. The Japanese drugmaker gained the rights to develop and commercialize linaclotide in Japan, Indonesia, Korea, the Philippines, Taiwan and Thailand. (See BioWorld Today, Nov. 11, 2009.)
Marketing, Sales Strategy Beginning to Emerge
Ironwood and Forest have prepared for months for the U.S. launch. Ironwood raised $79.2 million earlier this year in a public offering to buttress its bottom line. (See BioWorld Today, Feb. 13, 2012.)
The company reported $85.6 million in cash and equivalents as of June 30.
Hecht was short on specifics Thursday as Ironwood and Forest officials prepped for a hastily convened late afternoon conference call.
"We've been working for many months together on an integrated launch plan, and we feel very good about that," Hecht told BioWorld Today. "Details are going to have to wait for another day. Today's the day for the patients."
According to the National Institutes of Health, an estimated 63 million people are affected by chronic constipation that does not respond to standard treatment. Another 15.3 million people are affected by IBS, including IBS-C, characterized by abdominal pain and hard or lumpy stools at least 25 percent of the time and loose or watery stools less than 25 percent of the time.
All told, the patient population could represent a $6 billion opportunity, Ironwood and Forest officials predicted on the conference call.
Many patients with those diagnoses "have tried everything out there and are dissatisfied with available options," Hecht said. "Many have been suffering from pain chronically for years. They've been mischaracterized, until now, because there haven't been good treatment solutions."
A once-daily capsule, Linzess is designed to relieve constipation by helping bowel movements occur more often. In IBS-C, the drug also may help ease abdominal pain.
"In the final label, the FDA approved very good documentation of pain relief," Hecht said. "It's a very strong label that will enable us to effectively educate patients and physicians."
The drug was approved with a boxed warning that it should not be used in patients 16 and younger. As part of linaclotide's post-approval requirements, Ironwood and Forest agreed to a pediatric development program that will include additional nonclinical studies to characterize deaths observed in neonatal and young juvenile mice 1 to 3 weeks of age during nonclinical toxicology studies. Linaclotide did not cause deaths in older juvenile mice and was safely dosed up to 5,000 mcg/kg/day in nonclinical toxicology studies with adult models.
Ironwood and Forest officials said they expect to have product stocked and marketing under way well before the year-end holiday break.
The companies also said they would focus sales and promotional activities on high-prescribing primary care physicians and gastroenterologists.
From a manufacturing perspective, Ironwood is "fully prepared to launch in the fourth quarter," Hecht emphasized.
Once linaclotide is on the market Ironwood is expected to turn its attention to its internally developed pipeline, which includes IW-9179, a second-generation GC-C agonist slated to enter Phase II trials this year for painful disorders of the small intestine, such as dyspepsia and gastroparesis.
"We have a lot of work going on to broadly explore the area of GC-C agonists," Hecht confirmed.
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