By Karen Pihl-Carey

Genentech Inc.'s stock rose 18 percent Monday with news that the FDA approved for marketing the thrombolytic agent TNKase and with the company's regulatory submission for its anti-IgE asthma and allergy drug.

The stock (NASDAQ:DNA) closed at $128.56, up $19.437.

TNKase (tenecteplase) is indicated to treat acute myocardial infarction (AMI) and has the potential to cannibalize Genentech's Activase, analysts said.

Anti-IgE is a recombinant humanized monoclonal antibody to immunoglobulin E being developed jointly by South San Francisco-based Genentech, East Hanover, N.J.-based Novartis Pharmaceuticals Corp., and Houston-based Tanox Inc. as a therapy for asthma and seasonal allergic rhinitis.

"These are two important milestones for the company," said Jay Silverman, a senior analyst with Robertson Stephens in San Francisco. "Each one is important on its own, but together, they're just a great sign of the new product flow of Genentech."

With the approval of TNKase, physicians now will have a simpler way of treating patients with heart attacks, a condition that strikes more than 1.1 million Americans and causes about 500,000 deaths each year. While the product and Activase have shown similar results in trials, TNKase can be administered more efficiently.

"We are really pleased that TNKase has been approved by the FDA. It is the first thrombolytic to date that can be given over 5 seconds and in one dose," said Betsy Rosenberg, senior manager of corporate communications at Genentech.

Activase is the most widely-used thrombolytic over the past decade, Genentech said, but it involves a 90-minute accelerated infusion. It was approved for AMI in November 1987, acute pulmonary embolism in June 1990 and acute ischemic stroke in June 1996.

The approval of TNKase, which Genentech announced late Friday, is based on results of the ASSENT 2 (assessment of the safety and efficacy of a new thrombolytic agent 2) study, which involved 17,000 patients and compared a weight-adjusted dose of TNKase with Activase.

The study yielded mortality rates of 6.2 percent for each product. Side effects also were similar in each group. Both products showed a rate of .9 percent for intracranial hemorrhage. TNKase had a rate of 1.8 percent for stroke, while Activase had a rate of 1.7 percent.

"The important thing," Rosenberg said, "is ASSENT 2 demonstrated that non-intracranial major bleeding and the need for blood transfusions were lower in patients treated with TNKase compared to Activase."

Rosenberg said Genentech has no intention of removing Activase from the market because it is approved for two other important indications. "It will remain the only available treatment for acute ischemic stroke within three hours of symptom onset, and it will continue to be used by physicians for acute massive pulmonary embolism," she said.

Silverman said TNKase likely will cannibalize Activase in the AMI indication. He expects TNKase to have sales of $10 million to $15 million this year, rising to about $100 million next year. That will eat into Activase's sales, which were $236 million in 1999, Silverman said. TNKase also will take a share of the sales from Johnson & Johnson's Retevase, a double-bolus drug.

Matthew Geller, senior biotech analyst at CIBC World Markets Inc. in New York, also believes TNKase will cannibalize Activase sales. Together, the two products will record sales of $259 million in 2000, $280 million in 2001 and $300 million in 2002, Geller's firm estimates. While exact pricing of TNKase has not been announced, the wholesale list price per dose of Activase is $2,200, Rosenberg said. A launch of TNKase is expected in the third quarter.

It is under regulatory review in Europe as a treatment for heart attack. Upon approval there, it will be marketed by Boehringer Ingelheim GmbH, of Ingelheim, Germany.

TNKase also is being tested in four ongoing clinical studies involving more than 9,000 patients to evaluate various heart attack regimens in combination with the three GP IIb/IIIa inhibitors currently on the market - Cor Therapeutics' Integrilin, Johnson & Johnson's ReoPro and Merck's Aggrastat.

Anti-IgE Has "Multibillion Dollar Potential"

On Monday, Genentech, Novartis and Tanox said they submitted a biologics license application (BLA) for anti-IgE (rhuMAb-E25), a product designed for early intervention in allergies by binding to circulating IgE. IgE is an antibody that triggers the release of inflammatory mediators that cause allergy symptoms.

"This is really good news," Geller told BioWorld Today. "The filing is a little ahead of schedule. It's about a month ahead of what we expected. We think this is the blockbuster product in the Genentech pipeline with a multibillion dollar potential. We see nothing competitive-wise. This seems to do exactly what you want it to do without side effects. It's really a remarkable compound for both asthma and allergies."

Geller estimates anti-IgE, which recently was given the brand name Xolair in Europe, could be launched as early as mid-2001, with sales of $95 million that year and about $280 million in 2002. Projected peak annual sales of the product are more than $4 billion, Geller said.

Silverman said the product could reach $2 billion in sales by 2004, "one of the biggest drugs the industry has seen."

The BLA is based on data from three studies in children, adolescents and adults with asthma and three studies in adolescents and adults with seasonal allergic rhinitis, said Wendy Emanuel, a senior manager of corporate communications at Genentech. The Phase III program involved about 2,000 patients, she said.

In the asthma trials, treatment with anti-IgE showed a decrease in the frequency of asthma exacerbations, defined as symptoms requiring a doubling of inhaled steroids or initiation of oral steroids to maintain adequate asthma control.

"Particularly interesting is that 40 percent of anti-IgE patients completely withdrew from inhaled steroids during the trial, compared to only 19 percent of placebo patients," Emanuel said.

Phase II/III results showed patients with moderate to severe ragweed-induced seasonal allergic rhinitis who received 12 weeks of therapy experienced a statistically significant dose-related decrease in nasal and ocular symptom severity and frequency.

"The study also demonstrated that there was as much as a 50 percent decrease in the number of days patients required rescue medication in the 300 milligram group, compared to placebo," Emanuel said.

"You can virtually eliminate an allergy season by taking this drug," Geller said. "We think it's one of the most exciting biotech products to come along."

Novartis also has filed for marketing approval of anti-IgE in the European Union, Switzerland, Australia and New Zealand. Additional clinical data of anti-IgE will be presented in August at the European Respiratory Society meeting.

About 17 million Americans suffer from asthma, Emanuel said, and there are about 40 million Americans who have allergic rhinitis.

The collaboration between Genentech and Tanox came about after a long-running dispute, dating back to 1993, in which one side alleged breach of contract and the other patent infringement. They settled the actions in 1996 by deciding to pool resources, as each had an anti-IgE antibody in Phase II trials. Tanox had a collaboration already in place with Ciba-Geigy Ltd., a company that later merged into Novartis.