At the end of last week Ironwood Pharmaceuticals, Inc. (NASDAQ:IRWD) announced that the FDA has acccepted its supplemental new drug application (sNDA) for a 72 mcg dose of its chronic idiopathic constipation (CIC) candidate, Linzess. The drug is already approved in this indication, but the current approved format involves higher dosage concentrations, and in turn, is not being used to treat mild versions of the condition. If the agency approves the 72 mcg dose, it would expand the market for Ironwood’s Linzess, and could quickly improve the company’s bottom line going forward.
So, with this in mind, and ahead of the FDA’s decision, here is a look at the drug, and what an approval might mean for Ironwood, and a couple of big pharmaceutical partners with ties to the treatment in question.
So, then, let’s look at the science. Unlike some of the other development stage candidates we address here at Market Exclusive, there is nothing particularly glamorous about a CIC indication. This doesn’t mean, however, that the science behind the drug isn’t noteworthy, Specifically, in this instance, linaclotide, which is the scientific name for Linzess, is part of a family of drugs called GC-C agonists, and this is what makes it interesting. The acronym here stands for an enzyme called guanylate cyclase-C, which is present primarily on the surface of the intestine. Before Linzess, very little investigation into the effects and action that this enzyme has had been undertaken, and the chief scientific officer of Ironwood (Mark Currie, for those interested) was one of the first to take a proper look at how it might be used to address certain gastrointestinal conditions. The company designed and developed a host of GC-C agonists, of which the one that would turn out most successful was linaclotide, and carried the agonist through clinical development showing that the agonization it induced could not only play a part in reducing gastrointestinal pain (as yet, we don’t know exactly how, just that it does) but also increase fluid secretion in the bowels. This increased fluid secretion translates to improved stool transit, and in turn, reduces the symptoms associated with the indication in question – CIC.
So what is the deal with the lower dose? Well, as many as 35 million Americans are believed to suffer from some degree of CIC, but the currently approved dosage (145 mcg) is too strong a treatment for a large portion of these. It can induce a number of unwanted adverse events, specifically, diarrhea. By reducing the dose by a factor of 100%, Ironwood hopes to increase its potential target population through offering physicians the option to prescribe Linzess in the mild to moderate sufferers that currently fall outside the bracket that would justify the potential for adverse events associated with the current dosage.
As mentioned, the application is supplemental, and it is based on a phase 3 trial that pitched the 72 mcg dose against the currently approved 145 mcg dose or placebo across a 12 week period. A few key points arose from this trial. First, that across a population of more than 1200 patients, both doses demonstrated an improvement in spontaneous bowel movements over placebo. This established efficacy. Perhaps more importantly, at least as far as an approval in the lower dose is concerned, the rates of diarrhea and associated discontinuations were lower for the 72 mcg dose than for the 140 mcg dose. This means not only has the trial established efficacy, but also has quantitatively justified an application for a lower dose.
So what does this mean for Ironwood and its partners? Well, CIC is generally regarded as an unmet need outside of the currently available Linzess treatment, and as much as 60% of sufferers are not severe enough to justify the potential for AEs on the 145 mcg dose. If the 72 mcg dose gets approval, therefore, it could quickly double the market potential for the drug from a numerical standpoint. Price point remains unclear, but don’t expect too much of a reduction associated with lower dosing. Ironwood is partnered with Allergan plc Ordinary Shares (NYSE:AGN) in the US, and AstraZeneca plc (ADR) (NYSE:AZN) in China and wider Asia, so an approval from the agency come PDUFA should translate into some upside for all three companies. Of course, the likely primary benefactor will be Ironwood.
The date to watch? As yet, a specific date remains to be set, but Ironwood expects a decision during Q1 2017.