Washington Editor

The much-hyped dual kinase inhibitor Tykerb (lapatinib) has entered the regulatory review process, as GlaxoSmithKline plc filed for FDA approval in certain breast cancer patients.

Specifically, the London pharmaceutical firm applied to market its compound in combination with Xeloda (capecitabine, F. Hoffmann-La Roche Ltd.) for advanced or metastatic HER2 (ErbB2) positive breast cancer in women who have received prior therapy including its likely rival in this space, Herceptin (trastuzumab, from Genentech Inc.). The FDA has named Tykerb a fast-track product.

This is a first step in GSK's broader strategy with the drug, with studies under way employing it as an addition to front-line breast cancer treatment. Of note, two of those trials are testing whether its use with Herceptin-chemotherapy combinations could improve on those existing regimens. One is measuring time to progression as its primary endpoint, and the other is looking at response rates.

There also is a more head-to-head study of the two products in which Tykerb monotherapy is being compared to dual therapy with itself and Herceptin. Its primary endpoint is progression-free survival.

Herceptin generated $320 million in U.S. sales last quarter for South San Francisco-based Genentech, a 111 percent increase over last year's second quarter. It has been on the market since 1998 and is marketed in Europe by Basel, Switzerland-based Roche.

GSK plans to file for European approval by the end of this year for Tykerb, which inhibits the tyrosine kinase components of EGFR (ErbB1) and HER2 receptors.

The drug likely wouldn't cut too deeply into Herceptin's sales early on, given that this initial label is indicated for Herceptin failures, but the newer product's front-line development bears watching.

Many analysts have forecast Tykerb's blockbuster eventual potential.

Its underlying new drug application is based largely on pivotal data showing that the Tykerb-Xeloda combination extended patients' median time to progression to 8.5 months compared to Xeloda alone, which was about half as long, 4.4 months (p=0.00008).

Those results came from the open-label Phase III trial, which was stopped prematurely because of its early success, were first reported earlier this summer at the American Society of Clinical Oncology meeting in Atlanta. (See BioWorld Today, June 6, 2006.)

The oral small molecule also is being investigated in earlier-phase studies for treating a range of other solid tumors that overexpress ErbB1 and ErbB2, including renal cell and head and neck cancer.

On Monday, GSK's stock (NYSE:GSK) rose 23 cents to close at $55.58. Shares in Genentech (NYSE:DNA) traded up 3 cents to $79.02.