Silicon Investor (SI) -- The First Internet Community

STOCKTALK

We've detected that you're using an ad content blocking browser plug-in or feature. Ads provide a critical source of revenue to the continued operation of Silicon Investor. We ask that you disable ad blocking while on Silicon Investor in the best interests of our community. If you are not using an ad blocker but are still receiving this message, make sure your browser's tracking protection is set to the 'standard' level.

Biotech / Medical : Biotech Valuation -- Ignore unavailable to you. Want to Upgrade?

To: RCMac who wrote (6958)	8/23/2002 8:03:44 AM
From: Hank	Read Replies (1) \| Respond to of 52153

Iressa troubles spell woes for drug class - update -------------------------------------------------------------------------------- Scrip, August 22, 2002 The surprise failure of AstraZeneca's anticancer, Iressa (gefitinib; ZD1839), to show any survival benefit in the combination INTACT studies of non-small-cell lung cancer (NSCLC) has led analysts to slash their earnings forecasts for the product and cast doubt over the potential of this entire new class of anticancers. The results of the trial (see adjacent story) may mean the end for Iressa in NSCLC combination therapy - for which filings were due in the fourth quarter - but the company says it is still pressing ahead with monotherapy approvals. Iressa has already been approved in Japan as monotherapy in recurrent NSCLC and a 2002 launch in the US for this indication is planned, pending an FDA advisory panel review on September 24th. ...novel drug class Iressa is the most advanced of the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors in development for cancer. Others include ImClone Systems' Erbitux (cetuximab; licensed to Bristol-Myers Squibb and Merck KGaA) and OSI Pharmaceuticals' Tarceva (erlotinib; licensed to Genentech and Roche), both of which are in Phase III trials, as well as a number of other products further back in development (see table). Following the success of Novartis' targeted anticancer, the tyrosine kinase product Glivec (imatinib), there has been a lot of interest in the EGF receptor tyrosine kinases at cancer meetings over the past year or so because of their promise as a targeted therapy with fewer side-effects than conventional treatments. Iressa and similar agents work within the cell to target and block EGFR signalling, which is responsible for the growth and survival of cancer cells in NSCLC and other tumour types including colorectal, head and neck, prostate and breast cancers. The targeted mode of action means that side-effects are generally mild. Those of Iressa include diarrhoea and skin rash. Some experts are concerned that the INTACT data will deter doctors from conducting future combination trials with EGFR products. Dr Richard Sullivan, head of clinical programmes at the CRC in London, UK, says that the INTACT data are disappointing. But he believes there is still an important place for the EGFR tyrosine kinases in cancer therapy. "The bottom line is the news is not doom for all of these products. Tyrosinases are hugely important drivers of cancer and so are important targets for anticancer therapy," he said. The failure of INTACT does not spell failure for other EGFR tyrosine kinase inhibitors in combination with chemotherapy, since even subtle differences between the products can result in profound differences in the clinic, Dr Sullivan noted. There are still problems that need to be overcome with tyrosine kinase inhibitors, and we are still in the early stages of knowing how best to use them, he added. ...regulatory hurdles Despite their potential, regulatory agencies are generally more cautious about approving products in a novel drug class and some experts believe AstraZeneca may next face difficulty in gaining US approval for the monotherapy indication, because the IDEAL data may not be strong enough (Scrip No 2762, p 18). Indeed, Iressa is not alone in facing regulatory problems with its EGFR product. Delays for ImClone's Erbitux began last December, when an FDA panel rejected the BLA because it wanted more data. Since then, Erbitux has been delayed further and US approval is still some way off (Scrip No 2748, p 20). EGFR products in development Product Brand name Originator Phase gefitinib Iressa AstraZeneca III cetuximab Erbitux ImClone III erlotinib Tarceva OSI Pharma III EMD-72000 Merck KGaA II TP-38 Ivax II PKI-166 Novartis II Source = Pharmaprojects. Analysts at Morgan Stanley have reduced their global EGFR model to $3 billion in total sales in 2008 "to reflect diminished class potential". But although the INTACT failure was a shock, they say it is too soon to write off the whole EGFR inhibitor drug class. They believe the poor results could be due to patient selection or the high hurdle of improving on combination therapy in first-line use. Keen to distance itself from the news of AstraZeneca's failed trial, OSI has issued a statement saying that it remains on track with three Phase III NSCLC trials with Tarceva. Although both Iressa and Tarceva work by blocking the EGFR pathway, there are important differences between the agents and clinical programmes including structure, formulation, pharmacokinetics and Phase III design and dosing, OSI maintains. Its share price plunged by 57.1% to $14.05 on the failed INTACT trial, while ImClone Systems' fell by 10.6% to $8.26 on the news on August 19th. OSI says one trial with Tarceva monotherapy in refractory NSCLC patients and two in combination with chemotherapy are continuing and have "noteworthy differences" from the INTACT study. Tarceva is given at 150mg/day and the trials are powered for a 25% improvement in survival. SCRIP - World Pharmaceutical News FILED 22 August 2002 COPYRIGHT 2002 PJB Publications Ltd gene.com ms.com Copyright (c) 2002 PJB Publications, Ltd. Received by NewsEDGE/LAN: 08/23/2002 5:18 AM