By Randall Osborne
"Robust" is defined by Webster's as "strong and healthy; hardy; vigorous." It's a word used as often to describe Iowa farmhands, flour-dusted lady bakers, and Colombian coffees, as it is to describe biotechnology companies and their pipelines.
But nobody would deny that the modifier fits Genentech Inc. perfectly.
The thriving South San Francisco firm ¿ the world's first biotechnology company can boast that 14 industry products are based on its science, and Genentech itself markets and manufactures nine, including the flagship monoclonal antibodies Herceptin (trastuzumab) for metastatic breast cancer in patients whose tumors overexpress the human epidermal growth factor receptor2, or HER2, protein; and Rituxan (rituximab), the antibody marketed with IDEC Pharmaceuticals Corp., for relapsed or refractory low-grade or follicular, CD20-positive, B-cell non-Hodgkin's lymphoma.
With almost $1.3 billion in product sales last year, Genentech, more than half-owned by F. Hoffmann-La Roche Ltd., is surely robust, in the view of First Union Securities and everybody else. First Union, as an example, expects revenues to grow 19.5 percent per year for the next five years, with product growth of 23.1 percent per year during the same period, and diluted earnings to jump by 23.6 percent.
Genentech scored another win last week, when the FDA approved its thrombolytic agent Cathflo Activase (alteplase), a tissue plasminogen activator for restoring function to central venous access devices, as assessed by the ability to withdraw blood.
It's the only such agent for the indication, which can be a serious problem for cardiovascular patients ¿ about 5 million annually ¿ who require catheters.
Of those, about 1 million become occluded (more than half because of blood clots), and Activase off-label has been popular among physicians for several years, since the removal of Abbott Laboratories Inc.'s Urokinase from the market, and the growth has happened despite a drop-off in thrombolytic use, as doctors move toward interventional therapy instead.
Another Genentech thrombolytic product, TNKase (tenecteplase), which was developed for acute myocardial infarction, has been gaining ground, and approval of Cathflo ¿ $60 per 2 mg dose ¿ means a cheaper way to fix blocked catheters, which might otherwise need to be replaced at a cost that could be four or five times as much.
Sales of Activase and TNKase are expected by Wall Street to hit around $210 million for this year.
At the sam time, though, a trial began in California state court on allegations by City of Hope National Medical Center that Genentech owes at least $400 million in royalties based on work by two of the center's biologists, Arthur Riggs and Keiichi Itakura.
Both scientists were under contract with Genentech when insulin and human growth hormone were discovered, and the company has been paying royalties to the non-profit center for a couple of decades.
The 1976 contract between Genentech and City of Hope gave then-early stage Genentech rights to the patents on the pair of scientists' methods, and provided the cancer center with 2 percent royalties from resulting products.
City of Hope is now claiming it should have received royalties from all patented research coming out of the 1976 agreement. That would mean Genentech should have been paying royalties for (among others) alpha interferon, licensed by Genentech to Schering-Plough Corp.
Genentech, for its part, says the center's claim is too broad. Twenty-seven patent licenses are the subject of the fight, which is expected to last until winter.
Genentech is no stranger to legal skirmishes. About two years ago, the firm agreed to pay the University of California $200 million so that its dispute over a patent for human growth hormone would go away.
The firm also has battles pending with GlaxoSmithKline plc (the appeal of an earlier case, in which Genentech was victorious, related to Herceptin and Rituxan, and another case related to culturing Chinese hamster ovary cells); Chiron Corp. (regarding Herceptin); Pharmacia AB (a dispute before the International Chamber of Commerce, related to royalties due Genentech on human growth hormone); and Genzyme Corp. (over TNKase).
Through the artillery fire, Genentech charges onward.
Analysts expect Rituxan to keep making inroads in the lymphoma market, and Herceptin could surge when interim safety data are disclosed later this year on the monoclonal antibody when used with chemotherapy.
And there's more.
The company is readying supplemental data for the FDA on its biologic license application for Xolair (omalizumab), a potential blockbuster developed with Tanox Inc. for asthma and seasonal allergic rhinitis. In July, the agency said it needed additional information on Xolair, which Genentech said might be supplied from ongoing trials.
This week ¿ Tuesday ¿ an FDA advisory panel is expected to consider Zevalin (ibritumomab tiuxetan), a mouse monoclonal antibody targeted against the CD20 antigen found on normal mature B cells and cancerous B cells, and is conjugated to a yttrium-90 radioisotope. Developed by IDEC, it's administered with Rituxan, IDEC's non-radiolabeled chimeric antibody against CD20. Genentech has a co-marketing agreement for Rituxan in the U.S.
In May, the FDA asked for more data on Zevalin, but no more trials, and analysts are optimistic about a favorable outcome at Oncologic Drugs Advisory Committee. It's possible that IDEC will run into patent challenges from Corixa Corp. related to radiolabeled antibodies, but the picture still looks bright for Zevalin and, by extension, Genentech.
Also, by the end of this year or the start of next, Genentech said it hopes to submit, with partner XOMA Ltd., a biologics license application for Xanelim (efalizumab), a psoriasis treatment. Promising initial data from the second of two Phase III trials were disclosed last month at a scientific meeting.
Analysts expect FDA approval in October of Tracleer (bosentan), a twice-daily pill for pulmonary arterial hypertension, and its launch soon after. The drug, given an advisory panel's nod in August, was developed by Genentech and Actelion Ltd., and is expected to be the subject of an NDA in the fourth quarter for congestive heart failure.
And investors are looking forward to data from a Phase II study of TNKase with COR Therapeutics Inc.'s anti-platelet agent Integrilin (eptifibatide), developed for patients with acute coronary syndrome (unstable angina and non-Q-wave myocardial infarction), including those to be managed medically and those undergoing percutaneous coronary intervention. Data from that study are expected in November ¿ right about the time the City of Hope trial is anticipated to finish.
Will Genentech win or lose the court case? Pundits can debate endlessly from the sidelines, but the company, ever ready for whatever happens, keeps on ticking.
At the beginning of the year, Genentech CEO Arthur Levinson opened the J.P. Morgan H&Q Healthcare Conference in San Francisco with a rousing keynote luncheon speech.
Kill your clinical failures early, Levinson counseled attendees. It seemed easy for him to say, because the company seems to have had so few ¿ staying, as the overworked adjective has it, robust.