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Making renal disease a top priority
LONDON—AstraZeneca PLC got a boost to its pipeline in early October as it struck a deal with Fremont, Calif.-based Ardelyx Inc. for a worldwide exclusive license for Ardelyx's NHE3 inhibitor program, including the Phase II-ready lead compound RDX5791 that is aimed at irritable bowel syndrome and renal disease.
Under the terms of the agreement, AstraZeneca will pay a $35 million upfront fee, with development milestones of as much as $237.5 million related to launch and commercialization of potential drug candidates, as well as tiered, double-digit royalties.
Ardelyx will conduct clinical trials in Phase II trials for the NHE3 inhibitors, though AstraZeneca will assume the subsequent development costs. As part of the transaction, Ardelyx has secured an option to co-promote the product in the United States, subject to agreed limitations.
Additional financial details were not disclosed.
Ardelyx CEO Mike Raab tells ddn that it's a particularly good time for a deal like this in part because "given the increased incidence of diabetes and obesity and resulting kidney disease, many pharmaceutical companies have come to realize that therapeutics for the complications of renal disease may be one of the largest underserved market opportunities in medicine. That, coupled with the expiration of patent life for multibillion dollar drugs, has led several pharmaceutical companies to prioritize to the top of their in-licensing lists drugs for renal disease."
Add the recent safety failure of bardoxolone in Phase III clinical trials, "a drug with extremely high promise for renal patients," Raab notes, and that "points to the even more urgent need to find drugs that can impact this disease and improve outcomes for these patients."
He points out that AstraZeneca has been aggressive about pursuing novel medicines, making the company what he characterizes as "among the best possible worldwide partners for validating Ardelyx's unique approach to drug development," also having noted in a news release about the deal that he has been impressed with his interactions with AstraZeneca throughout the licensing process, adding to his confidence that the British company has the necessary commitment to develop the RDX5791 molecule successfully.
NHE3, or sodium-hydrogen antiporter 3, is a protein essential in the absorption of sodium in the intestines, and the NHE3 inhibitor RDX5791 is intended for the treatment of complications associated with end-stage renal disease and chronic kidney disease. Another notable point about RDX5791, Raab has noted, is that it is his company's "first clinical example of how our technology can be used to develop non-absorbed, small-molecule therapeutics."
Ardelyx has evaluated RDX5791 in a Phase IIa clinical trial in constipation-predominant irritable bowel syndrome (IBS-C) and in two Phase I clinical studies in healthy subjects for its ability to divert sodium absorption in the gastrointestinal tract. Through its unique mechanism of action, RDX5791 is believed to decrease the absorption of dietary sodium and thus divert sodium excretion from the kidney to the feces, sparing the kidney and the cardiovascular system from unhealthy exposure to both sodium and fluid accumulation.
It is on the basis of this mechanism of action, Ardelyx and AstraZeneca say, that they plan to develop RDX5791 for use in end-stage renal disease and chronic kidney disease in addition to IBS-C. They also have expressed an intention to explore development opportunities for other diseases that are a consequence of sodium and fluid overload.
"Building our pipeline is our number-one priority, and this agreement with Ardelyx presents an opportunity to leverage AstraZeneca's global capabilities in drug development and our commercial capabilities in cardiovascular disease, diabetes and now complications of diabetes," says Gunnar Olsson, vice president and head of CVGI Innovative Medicines at AstraZeneca, adding that the compound has the potential to meet a significant need among patients with renal complications linked to diabetes and other conditions who currently have limited treatment options.
AstraZeneca had already identified renal indications as an area with a large unmet medical need, Olsson notes. His company has evaluated different approaches and "identified mechanisms targeting sodium and fluid overload as an area we wanted to pursue," he explains. "We have been aware of Ardelyx for some time and identified them as having a program that is pursuing a relevant mechanism. In looking in more detail, we found the Ardelyx program to be very promising. In our interactions with Ardelyx, we found them to be a very capable, experienced and professional team. Moreover, it was clear that Ardelyx and AstraZeneca had good chemistry as potential partners."
Looking at the deal, Zacks Investment Research commented in an investor note that "We are encouraged by AstraZeneca's focus on the high-potential emerging markets. We are pleased with its efforts to expand its pipeline and portfolio through mergers and acquisitions." According to Zacks, this Ardelyx agreement—along with the acquisition of Ardea Biosciences Inc., a recent collaboration deal with Amgen Inc. and the expansion of a diabetes alliance with Bristol- Myers Squibb Co.—"all represent the company's efforts in this direction. We expect more such deals in the near term."
However, Zacks points out that it remains concerned about generic competition faced by the company's key products, noting that in 2011, the company lost revenues worth almost $2 billion to generics. The firm also added, "The weak late-stage pipeline at AstraZeneca coupled with slow Brilinta uptake also bothers us," leading to a Neutral recommendation from Zacks right now regarding AstraZeneca stock.