AstraZeneca will immediately stop promoting its oncologic Iressa and will inform physicians that Genentech/OSI's Tarceva demonstrated a survival benefit in refractory non-small cell lung cancer patients, CEO Tom McKillop said.

"We will draw to physicians' attention the fact that Tarceva is available and that physicians should really consider that for their patients," that Tarceva has "demonstrated a better survival compared to placebo and that we did not," McKillop said during a Dec. 17 analyst call.

In the 1,692-patient Iressa Survival Evaluation in Lung cancer trial, Iressa (gefitinib) failed to show a statistically significant survival benefit in the overall population (median survival 5.6 months for Iressa versus 5.1 months for placebo) and in patients with adenocarcinoma (6.3 months versus 5.4 months).

AstraZeneca has "volunteered to not promote [Iressa] while the discussions with the regulatory authorities are going on," McKillop said. AstraZeneca presented the ISEL results to FDA Dec. 16, he said.

Iressa will continue to be available to patients currently receiving the drug, the company said.

Iressa received accelerated approval in May 2003 for third-line treatment of patients with locally advanced metastatic NSCLC based upon the surrogate endpoint of tumor response rate. AstraZeneca conducted the ISEL study as a postmarketing commitment for Iressa's Subpart H approval.

FDA cleared Tarceva (erlotinib) Nov. 18 for treatment of refractory NSCLC under priority review (¹ Also see "Genentech/OSI's Tarceva Will Be Detailed Alongside Herceptin" - Pink Sheet, 19 November, 2004.). Tarceva demonstrated a two-month survival benefit relative to placebo in a Phase III trial (protocol BR21) (² Also see "Genentech/OSI Tarceva Shows Two-Month Improvement Over Placebo" - Pink Sheet, 8 June, 2004.).

It remains unclear whether FDA will withdraw Iressa's accelerated approval, McKillop said.

FDA and AstraZeneca will further analyze and discuss the results from the ISEL trial, McKillop said. "Until we do that we really have no idea whether or not Subpart H would be withdrawn and we would go back into IND status or not," he said.

FDA faces a major decision in deciding whether to withdraw Iressa's approval.

By withdrawing Iressa, the agency would send a strong message to manufacturers that accelerated approval still requires well-designed confirmatory trials that clearly demonstrate efficacy. However, opposition to withdrawal by patients and physicians who perceive that Iressa is beneficial would likely be strong.

Even if Iressa were not withdrawn, third-party insurers may be reluctant to reimburse for an oncologic that has not shown a survival benefit when there is an alternative (Tarceva) that has shown a benefit.

Division of Oncology Drug Products Director Richard Pazdur has expressed concern that companies use the accelerated approval pathway to gain approval based on minimal efficacy data.

Iressa's tumor response rate of 8.2% in the ISEL trial was comparable to the rate seen in Tarceva trials and the response rate seen in the Phase II IDEAL study, which FDA used to grant Iressa accelerated approval, the company said.

ISEL also followed earlier studies in finding an increased benefit for Iressa in patients of "Oriental" origin and patients who never smoked. Oriental patients came from a number of countries including Malaysia, the Philippines, Singapore, Taiwan and Thailand, the company said.

Oriental patients accounted for approximately 20% of the ISEL population (370) and exhibited a statistically significant survival benefit of 9.5 months for treated patients compared to 5.5 months for those on placebo. Approximately 12% of the Tarceva protocol BR21 population was Asian, AstraZeneca said.

"Very importantly," McKillop noted, "in the Caucasian population we are seeing almost nothing for Iressa" in terms of survival benefit.

AstraZeneca said that it did not expect the ISEL data to have significant financial impact. "Iressa…was selling pretty well, but we don't see the financial impact as very, very large for Iressa," McKillop said. Sales of Iressa were $113 mil. in the third quarter of 2004.

CFO Jonathan Symonds said that AstraZeneca's current Iressa inventory exposure is "around $70 mil….but it's by no means certain yet how much of that we will consider necessary to provide against," he added.

"I don't see any significant risk of" liability, McKillop said. "We have no reason to believe that there are any safety concerns" in the ISEL study other than those found in earlier trials, he said.

"There are patients that have had very significant benefit from the drug, therefore I wouldn't anticipate any substantial liability issues," he added.

In light of AstraZeneca's recent difficulties with Iressa and Exanta , McKillop outlined a strengthened regulatory risk management program within the company (see ³ Also see "AstraZeneca Refocuses On Risk Management, Elevates Development Oversight" - Pink Sheet, 17 December, 2004. ).

- Andrew Kasper

Iressa Promotion Halted; AstraZeneca To Highlight Tarceva Survival Benefit

More from Archive

More from Pink Sheet