Race for the Cure, and the Vaccine too

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These days it seems that everyone around me knows a family member, friend, neighbor, or congregation member who has battled breast cancer. Some come through, others don't, but all are impacted by it in one way or another. So, if you're like me, your spirits lifted when you read the headlines this week that heralded "New Vaccine Could Prevent Breast Cancer."

Without hesitation, I went to read the articles where I found out that the results being reported were from a study of 12 mice who had a genetic predisposition to tumors and are used as an 'animal model' of breast cancer in people. I had two reactions immediately. First, the media's headlines were a bit overstating the results. Second, I bet most people don't know what it will take to go from these promising results in mice to a vaccine to prevent cancer in humans.

So, in the spirit (or the footsteps?) of author Malcolm Gladwell, who recently chronicled the difficulties in developing cancer treatments in his article, "The Treatment" for the May 17th issue of the New Yorker, I thought that it might be useful to describe briefly what will be involved to take this vaccine candidate to a point where it can really help our friends and families.

First, the vaccine will need to be tested on humans. To gain approval for this clinical testing step, the US Food and Drug Administration will need to approve an Investigational New Drug application. Once the application is approved, the first step in clinical testing, called Phase 1 testing, can begin. Before a phase 1 study is approved, the FDA will review additional animal testing results of the vaccine's expected toxicity and teratogenicity (i.e., its ability to cause malformations in a fetus or embryo), and the detailed plans for the clinical study. These early steps go cautiously because the FDA takes precautions to be sure that the safety is clearly studied in a small number of people before it goes further and into larger numbers.

If the phase 1 results are acceptable and the vaccine meets standards of clinical acceptability, it will move into phase 2 testing where the primary goal is to get the right dosing and schedule for a protective immune response. These studies are likely to involve anywhere from a few dozen to a few hundred people.

The phase 1 and 2 testing generally take 2-4 years to complete and the costs are in the millions of dollars. The next step, phase 3 testing, is the really exciting part. It's at this point that you get the final answer on the vaccine's effectiveness. It's also the point at which big money is needed. Phase 3 trials can cost tens of millions of dollars to conduct (and they may not show an effective vaccine at the end).

Furthermore, if a company really thinks that the vaccine will be effective, they'll need to invest in building a manufacturing plant at the same time. Depending on the vaccine, this plant could cost from tens of millions to hundreds of millions of dollars to build. Regardless of the cost, companies expect that the building and validation of the plant may take at least 3-4 years to complete.

If the phase 3 trial shows that the vaccine is safe and effective, then it's back to the FDA for approval and licensing. With a licensed, approved vaccine, the company can start selling the vaccine and begin trying to earn back the money it invested. Bear in mind that the probability of successfully moving from each one of these steps to the next one is generally between 70-80%, according to a 1996 study (Nature Biotechnology 14, 591 - 593 (1996) doi:10.1038/nbt0596-591), so the probability of moving through all of these steps successfully - from mice to licensed product - is less than 20%.

Most researchers think that once licensed the hard work is done and that the vaccine will instantly eliminate the disease. However, our experience at the International Vaccine Access Center has shown that it can take as long to get the vaccine to the people who need it as it took scientists to develop the vaccine in the first place!

It's a long road ahead to realize the ambition of the lead researcher, Dr. Vincent Tuohy of the Cleveland Clinic, who says that if this vaccine is successful, "We could eliminate breast cancer." I'm hoping that it does succeed and in time to protect my two daughters, aged 5 and 7 today, and their friends from this devastating disease. In the meantime, I'm making a donation to Race for the Cure (for those in the Washington, DC area, the race is tomorrow on the National Mall), a charity that helps fund breast cancer research. I hope that some of it will go to Dr. Tuohy and the many other researchers who embark on the long, tedious, road to developing safe, effective vaccines.