Hot on the Trail
The cold and flu season is already upon us and the outlook is bleak.
Aside from getting a flu vaccine (and time is running out for that), there isn’t much to do now that the inevitable wintertime bugs are descending in force, other than treat the symptoms, get extra rest and drink plenty of fluids.
However, new ways of fighting back could be just a few years away. Several biotechnology and pharmaceutical companies are racing to get products on the market that take novel approaches to treating and preventing these annoying, and sometimes deadly, virus-borne diseases.
Some are developing drugs that attempt to block the common cold virus in its tracks by stopping it from multiplying in the nose and throat. Others are testing medications designed to keep the flu virus from spreading through the lungs.
Still others are working on improved flu vaccines that are sprayed into the nose rather than injected in the shoulder or that may be better tolerated than the current vaccines because of the way they are manufactured.
Adults on average can expect as many as four colds a year; children as many as eight, according to the American Lung Assn. While usually a mild illness, the common cold represents a potentially serious problem for the more than 20 million Americans who already have problems breathing because of emphysema, asthma or chronic bronchitis.
Influenza, which attacks the nose, throat and lungs, is a serious and sometimes deadly disease. Typically, it is accompanied by high fever, cough, chills and muscle ache. It saps your energy, and sometimes it takes weeks for sufferers to recover fully. If this turns out to be an epidemic season, 40 million Americans or more could come down with the flu and as many as 300,000 could be hospitalized. More than 40,000 Americans, most of them elderly, could die from flu-related illness.
Early signs indicate that the U.S. could be in for another epidemic season. By mid-November, 14 states had reported confirmed cases of flu; and deaths from pneumonia and influenza reported from 122 cities for the week ending Nov. 14 were “above the epidemic threshold,” according to the Centers for Disease Control and Prevention.
A growing understanding of how flu and cold viruses insinuate themselves in the machinery of their host’s cells has led to new strategies for treatment. No drug or vaccine is likely to be perfect, and the discovery of side effects could sink an otherwise promising treatment. However, the race is intense to bring effective new drugs and vaccines into a vast and potentially lucrative market.
Stopping Rhinovirus From Multiplying
The most frequent cause of colds is the rhinovirus--”rhino” from the Greek for nose. More than 100 varieties of the virus circulate among us, making it difficult to come up with a practical vaccine. And the ability of the body to fight off a second infection deteriorates over time, allowing a particular variety to strike repeatedly.
At the core of every rhinovirus is a short strand of RNA--the same stuff that directs the building of proteins in healthy human cells. The virus RNA is surrounded by a protective protein coat.
The rhinovirus cannot multiply without invading the cells that line the nose and throat. Inside the host cell, the virus throws off its protective coat and commandeers the cell’s machinery to duplicate itself.
Scientists at one Southern California biotechnology company have developed a compound, called AG7088, that blocks a vital enzyme produced by the rhinovirus. Called a “protease,” the enzyme cuts up a long chain of proteins into its active parts.
Block the protease, and the virus can’t make copies of itself and the infection stops there. After figuring the three-dimensional structure of the protease molecule, researchers at Agouron Pharmaceuticals in La Jolla designed a drug to neutralize its active regions. (Agouron used a similar strategy to design its successful anti-AIDS drug, Viracept.)
Test-tube studies have shown that AG7088 can stop the multiplication of all 46 types of rhinovirus checked so far--a sign that the drug could be effective against all the rhinoviruses. This month the company will begin testing the drug, delivered in a nasal spray to healthy volunteers.
Company officials acknowledge that the drug still requires several years of testing followed by a year or more of government review, but they are optimistic.
“If it works, it is going to be a blockbuster,” predicts Donna Nichols, vice president of Agouron.
Another biotech company, Pennsylvania-based ViroPharma, is using a different point of attack against the rhinovirus and a related virus that causes meningitis.
ViroPharma’s drug, called pleconaril, was designed to fill in a crevice or valley in the virus’ protein coat.
“It’s like putting a Popsicle stick in a Rubik’s Cube so that it can’t move,” explained Mark McKinlay, the company’s vice president for research and development. If the coat is locked in place and can’t be removed, the virus cannot multiply.
The company is far along in testing the drug in patients with viral meningitis, a disease of the brain and spinal cord caused by a cousin of the rhinovirus.
Last month, ViroPharma announced “encouraging” but inconclusive results in a trial of pleconaril pills for children with meningitis. The drug is also being tested in patients with severe colds caused by another member of the same viral family, and here the results, according to McKinlay, were “pretty black and white.” The pills stopped infections in all the healthy volunteers who were deliberately exposed to the virus, he said.
The company expects to apply for Food and Drug Administration approval for pleconaril for both meningitis and respiratory tract infections in the year 2000.
Other companies, including Bayer and Boehringer Ingelheim, have been trying to develop inhalant sprays or powders that keep the cold virus from attaching to nasal cells. The hope is that the drugs would tie up the virus, stopping the spread of infection.
Early results suggested that the sprays could reduce cold symptoms, but there have been questions about price and effectiveness.
Drug Companies Race to Develop Treatments
There are only two drugs currently on the market for treating influenza--amantadine and rimantadine; however, both work only against type A influenza--one of three distinct types of flu virus. Luckily, type A is the most common form.
The drugs are 70% to 90% effective against type A infection, according to the CDC. But to work, they must be taken daily throughout the flu season, which is far more expensive than a vaccine--as much as $100 a month instead of $10 to $20 for an annual flu shot. The drugs also can shorten the duration and severity of flu symptoms if taken within 48 hours of infection. But they cause serious side effects in some people, including delirium, hallucinations and seizures. Worse still, the influenza virus can develop resistance to the drugs, rendering them ineffective over time.
Because of the drawbacks, drug companies are racing to test and win approval for a new class of antiflu drugs. At least three companies hope to have products on retailers’ shelves within the next few years.
These drugs work by blocking a viral enzyme called neuraminidase, which is required for the release of new virus particles from infected cells. During an epidemic, these neuraminidase inhibitors could be used to prevent infection or to ease the severity of symptoms.
One version of the drug is a dry powder, which is inhaled by mouth like an asthma medication. Called Relenza, it will be marketed by drug giant Glaxo Wellcome. The drug was invented by an Australian biotech firm, Biota.
Last month, Glaxo released results of two trials of the drug, given to patients within 36 hours of the first symptoms of flu. Patients with confirmed cases of type A or B influenza recovered two or more days sooner and had less severe symptoms than those given a placebo powder, containing no drugs.
The company filed for drug approval from the FDA in October and hopes to begin marketing Relenza in time for the 1999-2000 flu season.
Another pill, dubbed GS4104, has been shown in tests to reduce the duration and severity of symptoms, according to Hoffmann-La Roche, a Swiss pharmaceutical company that hopes to begin marketing the neuraminidase inhibitor next year. The drug was developed by Gilead Sciences of Foster City.
“The most common way physicians treat the flu is to tell their patients to go home, take plenty of fluids and get plenty of bed rest,” Roche spokesman Charles Alfaro said. “With a product like GS4104 . . . the earlier the patients come in and start treatment, the sooner they are going to start to feel better.”
Trailing the other companies, Johnson & Johnson is trying to get its flu pill on the market within two years. The medication was developed by BioCryst Pharmaceuticals in Birmingham, Ala.
Working to Improve, Create Flu Vaccines
Public health officials believe that the best way to respond to the flu is to prevent it from happening. And every year, an FDA scientific advisory committee recommends a vaccine intended to give protection against the three flu sub-types thought to be most likely to strike the United States in the next season. Three companies produce the vaccines.
Several firms are now hard at work on improved flu vaccines.
Aviron in Mountain View has developed a vaccine nasal spray called FluMist. In September, Aviron officials reported that FluMist was 87% effective in preventing flu in children in a large-scale trial. The researchers also found 94% protection against ear infections, a frequent complication of the flu among children.
Company officials believe that a nasal spray will be more widely accepted than flu shots, particularly among youngsters, and vaccinating them may be the best way of preventing a widespread epidemic. “The flu peaks first in young children, then in adults and then in the elderly,” said Dr. J. Leighton Read, Aviron’s chairman and chief executive. “It marches through the population, starting first with our young friends.”
Aviron hopes to launch FluMist in the fall of 2000.
BioChem Pharma of Montreal is also developing a nasal spray vaccine--one containing killed viruses.
Protein Sciences in Meriden, Conn., is working on a vaccine using proteins made by the virus.
One advantage of the protein vaccine is that it contains fewer contaminants than the current viral vaccines, said Bethanie Wilkinson, the company’s director of virology and immunology.
Earlier this year, the company developed an experimental vaccine against the deadly “bird flu” that struck Hong Kong last year, and it is already being made available to laboratory and health care workers who come in contact with the virus.
