Larger Firms Join Race For AIDS Vaccine

questions about the wisdom of rushing into clinical trials WASHINGTON -- The first company to win permission from the U.S. Food and Drug Administration to test an AIDS vaccine on humans was an obscure biotech firm in West Haven, Conn. That step, taken in August 1987, was viewed as a great leap forward in the fight against AIDS and a coup by the four-year-old company, MicroGeneSys, in its race against two other firms. Yet some scientists believe that the company made a false start. Because not enough was known about how the virus worked in animals, they argue, the expensive clinical trials may turn out to be for naught. Indeed, three years later, Micro-GeneSys' vaccine still lingers in clinical trials. In the meantime, three competitors -- Bristol-Myers Squibb, Viral Technologies, and Immune Response --have received permission in the United States to test their vaccines on people. Around the world, numerous laboratories are injecting a wide array of vaccines into humans. In addition, many of these companies have sought major corporate sponsors to finance their participation in the clinical trials race. To be sure, the scientific challenges are formidable. Scientists hope to build in people an impenetrable immune defense against the AIDS virus by injecting pieces of the viral coat or inner core, some of which are genetically engineered. Identifying the right piece is particularly challenging because the chemical makeup of the virus is variable. But the decision to go with a vaccine candidate in clinical trials rests as much on financing and marketing strategy as on scientific progress. In fact, one group that market analysts put at the top of their list of contenders in the AIDS vaccine sweepstakes, Repligen of Cambridge, Mass., has not even applied to FDA to enter clinical trials and is critical of others that have. "We have taken a very careful and measured approach," says Repligen president and CEO Sanford Smith, whose company is backed by the pharmaceutical giant Merck and Co. "Some groups are clearly taking stabs in the dark, and that's not how we go about it. I don't understand why the FDA is allowing [MicroGeneSys and Bristol-Myers Squibb] to go forward [into clinical trials]. Why is the health care system being allowed to spend money on something that's not going to work?" The people at MicroGeneSys say their decision three years ago was not made in haste. Testing the vaccine in people was an outgrowth of a belief that the data were "necessary and sufficient" to go ahead, says the company's chief executive, Franklin Volvovitz, who founded the company in 1983. "Do we want to wait five years and perfect the animal models?" he says. "My own view is that's a very questionable value. "On one side you'll have people saying, `Let's look at what goes on clinically and let's compare that to other diseases.' And people on the other side who say, `Well, AIDS is a new disease and there's nothing like it. So let's perfect the animal model.' And during this time there are people getting infected who are ultimately going to die from AIDS. This is not an influenza epidemic," he says. With 5 million people in the high-risk population and estimated profits of $150 million the first year the vaccine hits the market, there's good reason for companies to hustle. More than 60 research institutes, large pharmaceutical firms, and small start-up companies are pouring billions of dollars into vaccine research. How they spend that money can make or break them. Conducting clinical trials is far more expensive than doing animal studies, scientists point out. Consequently, a decision to go into trials is tantamount to putting all one's eggs in one basket. Also, testing a vaccine that proves to be just partially effective on humans who might later be exposed to the HIV virus also raises ethical questions. "So, maybe it's better to go slow and steady," says Richard Purcell, a biotechnology consultant at Kline and Co. in Newark, N.J. Companies like Repligen, he says, "are all making sure they know everything they can about the vaccine before they go to clinical trials. They want to make sure that what they have is the best there is to put forward." Some companies find that they can put their best foot forward by linking up with another, larger firm. His task, says biochemist Allan Goldstein, chairman of the tiny Alpha 1 Biomedicals in Washington, D.C., is "to identify a much larger company that can translate our work into a setting where it really can be used commercially. These companies like Alpha 1 -- and there are hundreds of them -- are providing a great service." A number of larger firms have already joined forces with smaller companies to develop a vaccine (see box). Merck and Co. has hitched up with Repligen. Ciba-Geigy of Switzerland and the Chiron Corp. of Emeryville, Calif., have formed Biocin Co. Bristol-Myers Squibb has its subsidiary Oncogen, of Seattle, working on a vaccine. And Alpha 1 Biomedicals joined another small biomedical company, CEL-SCI of Alexandria, Va., to form Viral Technologies. Merck, Ciba-Geigy, and Bristol-Myers Squibb bring years of experience in developing and marketing drugs and vaccines, as well as deep financial pockets to back up the scientific ingenuity in the smaller companies. But these alliances can also represent a merging of research prowess. For example, "Chiron knew a lot about infectious diseases, and Ciba-Geigy had a very good program in adjuvants," says Chiron spokesman Larry Kurtz. Adjuvants are chemicals that are added to vaccines to jump-start the immune system. According to Repligen's Smith, Merck was interested in his company because it was making a vaccine from a genetically engineered fragment of the viral envelope protein. That approach, scientists believe, is safer than candidate vaccines that use a chunk of killed or weakened virus. Of the leading companies, Repligen is the only one not to have begun human testing of the vaccine. Instead, it has funneled its resources into animal studies and into fine-tuning the vaccine so that it protects against many different strains of the AIDS virus. Earlier vaccines were not so refined. "Our goal has not been to get into clinicals," says chemist Walter Herlihy, senior vice president of research and development at Repligen. "It is to get out of clinicals," he says, and into the market. But scientists at MicroGeneSys think they did the right thing three years ago by jumping quickly into clinical trials. Because the company has specialized in developing vaccines and diagnostic products for malaria, Dengue fever, and hepatitis B, says Volvovitz, it had a unique vaccine technology that was ready to be tested on humans. Even if it fails, he adds, the results will help the company's other vaccine research. Actually, the reason that Micro-GeneSys began clinical research early may have less to do with its assessment of its science and more to do with its identity as a small, upstart company. These firms do not have a lot of extra financing to support years of preclinical product development, and thus the payoff for being first on the market looms very large. "People like MicroGeneSys rushed in to clinical [trials] without a whole lot of money," says Purcell. "That is what that sort of entrepreneurial company does. If they win, they're golden. If they don't, well, they gave it their best shot." Not all small companies have to think along those lines. Repligen, another startup, may be small, but it has the advantage of being backed by Merck, one of the biggest pharmaceutical outfits in the business. "A major pharmaceutical firm comes to the decision to develop an AIDS vaccine with a different attitude from the one taken by a small biotech firm," says Mark Dibner, director of biotechnology information at the North Carolina Biotechnology Center. "The issues each faces are different. Pharmaceutical companies are in it for the long haul. Even if a vaccine doesn't work, they see the potential spin-offs in other vaccine markets, in terms of the technology they develop," he adds. With $5 million from Merck in 1987, plus annual payments of $2.5 million and an extra $3 million awarded for good progress last year, Repligen can afford to think like a big company. However, not all companies in the AIDS vaccine race fit neatly into this pattern. Take Bristol-Myers. In November 1987 it became the second company to begin clinical trials, just three months behind Micro-GeneSys. Again, the skeptics argued that too little was known about the virus, and some analysts still wonder why it moved forward so soon. "Bristol-Myers is a company that could take its time, but for some reason, it hasn't," says analyst Purcell. Although company officials were unavailable to comment, the reason may be as simple as the lure of new knowledge. "MicroGeneSys has learned a lot [in clinicals], such as what dose of vaccine it takes to get an antibody response, the safety results, quality of response, and level of antibodies," says Gerald Quinnan, Jr., deputy director of FDA's Center for Biologics Evaluation. Bristol-Myers Squibb is gathering the same useful information. Indeed, Repligen's decision to wait may be purely commercial. Among other things, Quinnan adds, it allows them "to sit back and see what happens."

Larger Firms Join Race For AIDS Vaccine

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