Article & Journal Resources

Novartis May Be One of the First
To Get a Payoff From Latest Know-How
By JEANNE WHALEN
December 17, 2007; Page A12

As advances in gene-mapping have revealed more about the underpinnings of life, pharmaceutical companies have been trying to translate that knowledge into product discoveries.

Novartis AG is among a few companies now showing results. Its work is raising the potential for a source of new drugs and vaccines for an industry facing dry research pipelines and aging product portfolios.

A Novartis vaccine for a deadly form of meningitis is proving effective in human trials. Its researchers mapped the genes of the bacterium that causes meningitis B and used the map to develop a vaccine that has produced encouraging results in its first trial in infants, the company reported at a meningitis conference in London on Nov. 8. Out of 150 babies in the United Kingdom who received two shots of the vaccine, 60% to 90% experienced a strong level of protection against three common strains of meningitis B. The test is continuing, with the infants scheduled to receive another two shots.

Novartis plans to move its experimental vaccine into a much-larger test involving thousands of children next year, says Rino Rappuoli, an Italian scientist who heads Novartis's vaccine research. The vaccine is still in midstage, or Phase 2, trials and could still fail in further studies. If all goes well, the vaccine could reach the market by 2010. "I find this incredibly exciting," says Craig Venter, the American biologist who helped Novartis decipher the genetics of meningitis B and went on to map the human genome. "Hopefully, this can be a model that can be repeated."

The science of gene-mapping is called genomics. Scientists began mapping the genes of bacteria in the early 1990s, and Novartis and other drug companies are now using these maps to find ways to kill the bacteria with vaccines.

Intercell AG of Austria is testing a number of vaccines that it developed from gene maps, including one for pneumococcus, which causes pneumonia. Intercell and Merck & Co. are jointly developing another genomically derived vaccine for staph infections. And GlaxoSmithKline PLC also has used genomics to develop vaccines against streptococcus and the bacterium that causes meningitis B; both are in early-stage testing.

After figuring out how to map bacteria, scientists moved on to decode the more complicated genetics of humans, publishing a full map in 2003. Some drug companies hoped the human genome would help them speedily discover new drugs.

That hasn't happened as quickly as some predicted. Researchers in the past two years have identified about 10 human genes that appear linked to diabetes, for example, but that knowledge hasn't produced a drug. One reason: dozens of additional genes probably also play a role in the disease, and it is unclear which genes a drug should target. Also, poor diet and other behavioral issues contribute to diabetes. And a drug can take as many as 10 years to develop.

"Getting these hints from genetics isn't really close to producing a drug," says David Goldstein, a geneticist and director of Duke University's Center for Population Genomics and Pharmacogenetics. He and others say the human genome is helping scientists understand diseases better and should lead to new drugs down the road.

Novartis and other pharmaceutical companies are under big pressure to invent new drugs and vaccines. Many of the industry's biggest products are facing generic competition, leaving companies vulnerable to a sharp fall in sales. Several of Novartis's drugs were hit by generic competition this year, contributing to poor third-quarter earnings at the company. Excluding a one-time gain from asset sales, profit fell 12% over the year-earlier quarter to $1.57 billion.

A meningitis B vaccine could be good business for Novartis. French drug maker Sanofi-Aventis SA says it expects its vaccine for other forms of meningitis to reach global sales of €400 million, or about $580 million, this year. In a research note last year, Bear Stearns estimated that a meningitis B vaccine for infants could reach sales of as much as $3.5 billion a year.

Meningitis B is a devastating and unpredictable strain of meningitis, a potentially lethal infection in the membranes surrounding the brain and spinal cord. It strikes between 20,000 and 80,000 people a year world-wide, killing 2,000 to 8,000 of them within hours of infection. Many of its victims are under one year of age. Those who aren't killed by the disease can suffer brain damage, hearing loss and loss of limbs.

Scientists spent decades trying to find a vaccine using traditional methods, which include cultivating the pathogen and dissecting it to identify the parts important for inducing immunity. Dr. Rappuoli says he got the idea of using a gene map in 1995, when Dr. Venter changed science by publishing the first gene map of a living species -- the bacterium H. influenzae, which can cause pneumonia. Dr. Rappuoli figured if he could understand the genetic makeup of the microbe that causes meningitis B, he would have an easier time finding ways to attack it.

At the time, he was running vaccine research for Chiron Corp., which was partly owned by Novartis. Keen to build its vaccines business, Novartis paid $5.4 billion in 2006 to acquire full control of Chiron. Dr. Rappuoli asked mutual friends to get in touch with Dr. Venter to see if he could help with the meningitis B bacterium. In 1996 the Italian flew to the U.S. to meet Dr. Venter at the Institute for Genomic Research, the center he founded in Rockville, Md. "I told him it's an interesting disease. People die, children die. And maybe we can help," recalls Dr. Rappuoli.

Dr. Venter, who was paid for his work, agreed to use the institute's automated gene-sequencing machines to decode all the genes in the meningitis B bacterium. With the map in hand, Dr. Rappuoli and his team spent two years analyzing the more than 2,000 genes.

Dr. Rappuoli says his scientists knew roughly what they were looking for: genes that would direct the body to make proteins that would generate antibodies capable of killing the bacteria. They used high-speed computers to home in on 350 such genes on the surface of the bacteria.

Then they began the years-long process of immunizing laboratory mice with all of these proteins. They found that several of the proteins stimulated a powerful immune response in the mice.

The researchers used the most potent proteins to make an experimental vaccine and began testing it in humans in 2002, starting with adults and then adolescents. Then they moved to infants.

Simon Kroll, a professor of pediatrics and molecular-infectious disease at Imperial College London, said the preliminary results in infants look "very promising indeed" but need to be confirmed by larger trials. Harold Lambert, an infectious-disease expert and medical adviser to the Meningitis Research Foundation, said he is also encouraged by Novartis's results. Neither doctor receives funding from Novartis.

Write to Jeanne Whalen at jeanne.whalen@wsj.com