By Lisa Piercey

Special to BioWorld Today

The FDA's Oncologic Drug Advisory Committee's unanimous thumbs-up yesterday for Genentech Inc.'s Herceptin (trastuzumab) as a treatment for metastatic breast cancer caps a phoenix-like resurgence for monoclonal antibodies in recent years — and, ironically, may make the South San Francisco company all the more attractive for acquisition by its majority shareholder, Hoffman-La Roche Ltd.

It's also a small bit of good cheer for the beleaguered biotechnology sector.

"Any approval today is spectacular because there's a sea of negative news out there," said Steven Burrill, CEO of Burrill & Company, a private merchant bank based in San Francisco. The industry has lost about a quarter of its market value in the last two weeks alone, he said.

Though the news boosted Genentech's share price (NYSE:GNE) by $2.25 per share over the last two days — it closed Thursday at $67.50, up $0.75 — the company's stock tends to respond sluggishly to news events, due to the terms of Roche's put/call option, which caps the stock at $82.50 per share. Nonetheless, analysts say Herceptin is a major breakthrough for molecular biology and a solid success for the company.

It's The Decade Of Antibodies, Analyst Says

Herceptin is a humanized monoclonal antibody against the protein HER-2. Overexpression of HER2 is associated with a particularly aggressive form of breast cancer that afflicts about 25 to 30 percent of women with metastatic breast cancer.

Jeffrey Casdin, CEO of New York-based Casdin Capital Partners and a longtime industry observer, told BioWorld Today the 1990s have been "the decade of antibodies." If approved by the FDA, Herceptin will join the ranks of three FDA-approved therapeutic monoclonal antibodies developed by biotechnology companies: Malvern, Pa.-based Centocor Inc.'s ReoPro for acute cardiovascular disease and Remicade for Crohn's disease; and Genentech's own Rituxan for the treatment of refractory or relapsed low-grade non-Hodgkin's lymphoma. Since its launch late last year, Rituxan has generated sales in excess of $70 million.

Monoclonal antibodies, once hailed as potential "magic bullets" to cure a vast array of diseases, fell into disrepute after several high-profile products flopped, such as Centocor's infamous HA-1A and Berkeley, Calif.-based XOMA Corp.'s E5, both developed to treat sepsis. But once immunogenicity problems were solved by the creation of humanized antibodies and targeting became more precise, the field was resurrected.

"Credit ought to go to [Genentech CEO] Art Levinson for boiling down the pipeline at Genentech, focusing in on the top product candidates and getting the job done," said Casdin. "Unfortunately for Genentech, successes like this just make them all the more attractive to Roche." Roche, of Basel, Switzerland, which currently owns about 66 percent of Genentech, has a call option that expires June 30, 1999, to buy the remainder of the company.

The option, which one analyst likened to a "sword of Damocles" hanging over Genentech, has caused some investors to lose interest in the firm.

Genentech spokeswoman Marie Kennedy said the company expects FDA action on Herceptin by early November, and analysts anticipate a product launch by December. Herceptin was reviewed by FDA under the fast-track system for drugs that treat serious and/or life-threatening diseases, a system put in place by last year's FDA Modernization Act. The fast-track route requires FDA action in a six-month time period and Kennedy praised the approach. "It's always better to be working within a deadline," she said.

Herceptin Marketing Could Bolster Oncor's Test

Oncor Inc., of Gaithersburg, Md., jumped on the good news bandwagon by issuing a press release stating that it expects to benefit from the advisory panel's recommendation to approve Herceptin. Oncor said it currently markets the only FDA-approved gene-based breast cancer detection test, called Inform, which identifies the presence or absence of increased copies of the HER2/neu gene. Oncor's prognostic test was approved in December of 1997 for predicting the risk for recurrence of breast cancer.

Today, the FDA's Hematology and Pathology Devices Panel and the Immunology Devices Advisory Panel will review a similar test developed by Dako A/S, of Copenhagen, Denmark, in collaboration with Genentech. The Dako test is a slight modification of the test used by Genentech in the clinical trial to determine the eligibility of patients for Herceptin treatment.

Roche last month acquired exclusive marketing rights for Herceptin outside of the U.S. for an up-front fee of $40 million, plus cash milestones based upon European regulatory progress.

The advisory panel, voting 11-0, advised the FDA to approve Herceptin as a single agent in second- and third-line therapy, and in combination with paclitaxel in first-line therapy. It voted 9-2, however, in deciding the risks outweigh the benefits of using Herceptin with anthracycline. *

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