AstraZeneca's product development and regulatory affairs overhaul will include a review of ongoing Phase III programs for Galida , Cerovive and Symbicort .

"We will be including a review of Cerovive, of Galida and of Symbicort U.S. programs," CEO Tom McKillop said Dec. 17 during an analyst call.

Galida (tesaglitazar) is a dual peroxisome proliferator-activated receptor agonist in development for the treatment of type 2 diabetes. Cerovive (NXY-059) is being developed for treatment of acute ischemic stroke. Both are new molecular entities.

The company's Phase III portfolio also includes Symbicort (budesonide/formoterol), a combination of AstraZeneca's Pulmicort and Schering-Plough's Foradil , in development for asthma and chronic obstructive pulmonary disorder.

Review of those clinical programs will be one the responsibilities of former Exec VP-Product Strategy & Licensing John Patterson, who has been promoted to the board-level position of exec director-development effective Jan. 1.

The move to place the responsibility for product development under a board-level position is part of AstraZeneca's broader refocusing of its clinical and regulatory activities following development hurdles for two significant products: the anticoagulant Exanta and the oncologic Iressa .

"AstraZeneca is committed to the development of innovative medicines, but Exanta and Iressa, two products based on breakthrough science, have suffered setbacks," McKillop said.

AstraZeneca announced the same day that a confirmatory Phase III trial evaluating Iressa (gefitinib) failed to show a survival benefit in patients with lung cancer (see ¹ Also see "Iressa Promotion Halted; AstraZeneca To Highlight Tarceva Survival Benefit" - Pink Sheet, 17 December, 2004.). Iressa was approved in May 2003 based on a surrogate endpoint.

Exanta (ximelagatran) received a "not approvable" letter in October following a negative review by FDA's Cardiovascular & Renal Drugs Advisory Committee (² Also see "Exanta “Not Approvable” Decision Leads To $80 mil. Charge" - Pink Sheet, 21 October, 2004.).

"Following the non-approval of Exanta by FDA, we accelerated a significant program of change in the development and regulatory functions, based on the learning from these and other experiences," McKillop said.

Patterson's board-level appointment "is a further step in this process," McKillop said.

In his new role, Patterson will oversee "the design and implementation of all clinical and regulatory programs with emphasis on rigorous risk management and risk assessment," the CEO said.

Patterson will also assume responsibility for the "implementation of substantial changes to the clinical organization and its processes" and the "improvement of our regulatory capability and our effectiveness in interactions with regulatory authorities," he said.

"The kind of company that AstraZeneca is is, I think, a very innovative one. We put an enormous importance on innovation and creativity," McKillop said.

"I am not sure that we have put the same weight on challenge, to use that word," McKillop said. "I am not sure that we have been really taking apart the clinical programs from the point of view of 'where are all the risks?' and 'have we really optimized the risk management of the whole program as well as we might?'"

"Coupled with that is this whole question of our interaction with the regulatory authorities," the CEO said.

AstraZeneca needs to determine if the company is "actually asking ourselves and asking the regulatory authorities the difficult questions. Are we really addressing and sharing those kinds of questions with the regulatory authorities early enough?"

Although McKillop's remarks focused on Exanta and Iressa, one of the most significant challenges currently facing AstraZeneca relates to safety questions surrounding Crestor (rosuvastatin).

The cholesterol-lowering agent has become the center of a broader debate over FDA's postmarketing surveillance system following the withdrawal of Merck's Vioxx (³ Also see "Public Citizen Takes Aim At Crestor DTC Ads Defending Statin's Safety" - Pink Sheet, 26 November, 2004.).

Crestor has also been a flashpoint for debate over direct-to-consumer advertising.

McKillop has acknowledged the potential for drug companies' marketing efforts to undermine R&D. The CEO recently said manufacturers' promotional spend is roughly double that for R&D, noting that those figures make it hard to "use the R&D argument successfully."

Those remarks came shortly after FDA Acting Commissioner Lester Crawford cautioned against running DTC ads that make comparative claims (⁴ Also see "DTC Ad Comparative Claims Draw FDA Criticism, Even With “Scientific Basis”" - Pink Sheet, 16 November, 2004.).

A TV ad for Crestor describes the product as "clearly the best" when compared to other statins in a head-to-head study (⁵ Also see "AstraZeneca Launches New Crestor DTC Ad Campaign" - Pink Sheet, 21 October, 2004.).

AstraZeneca appears to have recently reduced the number of national ad buys for Crestor. The company said it has not halted the rosuvastatin campaign.

- Steele Thomas

AstraZeneca Refocuses On Risk Management, Elevates Development Oversight

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