Out with gout

SAN DIEGO—AstraZeneca PLC and Ardea Biosciences Inc.recently announced a definitive merger agreement by which AstraZeneca willacquire Ardea for $32 per share, for a total cash aggregate of approximately$1.26 billion. The price represents a 50-percent premium over the one-monthvolume-weighted average price of Ardea's stock, and a 54-percent premium overthe closing price on April 20, 2012.

The boards of directors of both companies have unanimouslyapproved the terms of the merger agreement, and Ardea's board has recommendedthat the company's shareholders approve the transaction. Those of Ardea'sshareholders representing approximately 30 percent of the current totaloutstanding shares have entered into a voting agreement with AstraZeneca infavor of the deal.

The acquisition gains AstraZeneca a strong gout program,including Ardea's most clinically advanced drug candidate, lesinurad (formerlyRDEA 594), which is currently in Phase III development as a treatment for thechronic management of hyperuricemia in gout patients. Lesinurad is a selectiveinhibitor of URAT1, a transporter found in the proximal tubule cells of thekidney that regulates the excretion of uric acid from the body. It is beingstudied as an add-on treatment to allopurinol (the standard gout treatment), asa monotherapy and as an add-on treatment to febuxostat in patients withtophaceous gout.

"We are delighted to be joining AstraZeneca," Barry D.Quart, president and CEO of Ardea, said in a press release. "From our earliestinteractions, we were impressed with the quality of AstraZeneca's people, andwe are confident their commercial strength and global reach will help realizethe full potential of our programs. The Ardea team and I are committed tohelping complete development and working to secure registration for lesinurad."

Ardea's gout program also includes RDEA3170, anext-generation selective URAT1 inhibitor currently in Phase I development.

"These projects offer an excellent opportunity to leverage AstraZeneca'sspecialty and primary care sales and marketing capabilities, as well as ourpresence in the U.S. and in key markets around the world—includingopportunities in China and Japan," says Christopher Sampson, a spokesman forAstraZeneca.

According to Stephen Davis, executive vice president andchief operating officer of Ardea, the combination of lesinurad with allopurinoloffers significant efficacy increases for treating gout patients. Allopurinol,he explains, functions by reducing the body's production of uric acid, which iselevated in gout and causes painful joint inflammation. However, "about 90percent of gout patients don't have a problem with production of uric acid,they have a problem with excretion," Davis says.

The situation is similar to that of a bathtub with thefaucet on and the drain open, he explains, and allopurinol partially closes thefaucet.

"What's not often appreciated is drugs like allopurinol …when you close the faucet, there's a feedback mechanism that also closes thedrain a little bit," he says. "Now, the net benefit is good, you have more ofan effect on the production than on the excretion, but it's taking a situationwhere these people aren't excreting enough and from that perspective making itworse. Again, the net effect is good, but it's not as effective as treatingpatients with combination therapies."

Combining lesinurad with allopurinol, Davis notes, keeps theproduction at its lowered level, but also opens the "drain" completely. InPhase II studies, when lesinurad and allopurinol were administered together,"about 85 to 90 percent of those patients then got to the medical target … it'sa very profound effect that we see when we combine these two mechanisms."

Pursuant to the acquisition, Ardea will maintain its SanDiego facilities as a standalone, functioning subsidiary to "secure delivery ofthe lesinurad Phase III program, regulatory submission and approval," accordingto Sampson. The transaction is subject to customary regulatory approvals andshareholder approval, and is expected to close in the second or third quarterof 2012.

"Put simply, AstraZeneca's strategy is to be a focused,integrated, innovation-driven, global, prescription-based biopharmaceuticalbusiness. Critical to our success is bringing to market innovative,differentiated medicines either from our own labs or through partnering andacquisition," says Sampson. "Late-stage opportunities like lesinurad are a goodstrategic fit with our business because they can leverage our commercial strengths,allowing us to add real value to the asset. Management has been clear that weare actively pursuing product licensing deals, more partnerships with industrypeers, like the Amgen deal, and smaller acquisitions like Ardea. For us,partnering and externalization have become a way of life."

AstraZeneca and TheMedicines Company announce global collaboration in acute ischemic heart disease

LONDON—In late April, AstraZeneca PLC also announced aglobal collaboration with The Medicines Company to develop acute ischemic heartdisease compounds, the first part of which is a U.S. co-promotion deal forAstraZeneca's oral antiplatelet medicine BRILINTA.

Under the terms of the global collaboration, a jointcommittee has been established to prepare and deliver global development andcommercialization plans related to BRILINTA and The Medicines Company'sAngiomax (bivalirudin) for injection and cangrelor, which is in development asan acute intravenous antiplatelet agent.

Implementation of these plans is subject to furtheragreements between both parties.

Under the terms of the co-promotion agreement, The MedicinesCompany sales force will begin supporting BRILINTA in May 2012. This willcomplement the AstraZeneca sales team's promotion of BRILINTA to U.S. hospitalcustomers and practitioners whose patients with acute coronary syndrome (ACS)may benefit from the therapy. AstraZeneca will pay The Medicines Company $15million per year for performing pre-agreed commercialization activities, withup to an additional $5 million per year paid if performance thresholds are met.

"The Medicines Company is a respected organization with astrong network in interventional cardiology," said Lisa Schoenberg, vicepresident of U.S. sales and marketing for AstraZeneca's Growth Portfolio unit,in a statement. "We have laid the groundwork for BRILINTA in the U.S. withstrong managed market access, as well as hospital formulary and protocolaccess, such that now is the right time to bring this important medicine tomore patients with ACS through additional support in the acute setting."