Iressa: In Japan, The Only Country Where This Novel Cancer Therapy is Approved, Death Rate is Unexpected and Worrisome.

Coverage beginning: 25 Sep 2002

Last update: 11 Feb 2003

Iressa (gefinitib, Zd1839) is an Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase Inhibitor with great potential in theory for treating solid tumors. The drug is selective for the HER1-TK subtype of tyrosine kinases, the so-called HER family. Phase II clinical trials are currently ongoing at City of Hope National Medical Center (Duarte CA) for bronchioloalveolar lung cancer (BAC). Phase I trials were carried out at the Dana Farber Cancer Institute in Boston.

In Japan the death toll has climbed to 39 amid regulatory concerns about the slowness of reporting severe adverse events. The product is being developed by Astra-Zeneca.

Interestingly, Doctor's Guide reports "AstraZeneca announced today that the Oncologics Drugs Advisory Committee (ODAC) to the U.S. Food and Drug Administration (FDA) have recommended accelerated approval for Zd 1839 (Iressa, gefitinib) for the treatment of advanced non-small cell lung cancer (NSCLC) after disease progression, following at least two chemotherapy agents."

Update 16 Nov 2002: AstraZeneca emphatically states that not only is Iressa planned to remain on the market, there are no slowdowns expected in the FDA approval process. Reuters, Dow Jones, AstraZeneca

Update 11 Feb 2003: As Japanese physicians were alerted to the possibility that Iressa (Generic name: Gefinitib) was linked to patient deaths, deaths previously not thought to be linked to this drug were reported, causing an increase in the death toll to 173. Of the 23,5000 patients exposed to the drug, 471 have developed serious cases of pneumonia. The official tally in December 2002 was 124, according to the Japanese Health Ministry spokesperson Tatsuo Kurokawa. After guidelines for prescribing Iressa were tightened by the Japanese government, there have been 2 deaths among 10 patients who developed the characteristic side effects between Dec 27 and Jan 24. The drug is on the fast track for FDA approval apparently propelled by impatience from AstraZeneca who insisted that Japanese post-marketing experience would not be linked to FDA approval. Nonetheless FDA appears to be monitoring the situation carefully before granting approval. Since Iressa targets a deadly form of cancer in its late stages, even this high death toll (about 0.7%) does not preclude approval; but the label will need to carry strong warnings and the eligible patient population will shrink.

Coincidentally, AstraZeneca applied for European Union approval (with EMEA) of Iressa.

Iressa represents a bold new approach to therapy of cancer, being an epidermal growth factor receptor - tyrosine kinase inhibitor.

*** POSTED FEBRUARY 12, 2003 ***