Like many people starting out in the biotech industry, I wanted to make an impact on people’s lives by developing life-changing therapies. But I’ve become disappointed by what I believe are too many companies pushing mediocre and me-too drugs, also known as copycat drugs, into clinical development where they will likely fail.
Clinical trials are more than a way to test new therapies. They offer very sick people hope and a chance for more time with their loved ones. Lately, the drug development process has turned into an exercise in me-tooism — at patients’ expense. It’s time to shift the focus back to those who matter most.
During a recent panel discussion, Richard Pazdur, who directs the Food and Drug Administration’s Oncology Center of Excellence, called for companies to reevaluate their current clinical trial processes. He rightfully criticized the industry’s repeated attempts at testing an approach in a disease indication after it has failed multiple times.
Pazdur used the example of checkpoint inhibitors (drugs that target PD-1 or PD-L1) for multiple myeloma. Three recent studies were conducted close together, and although they were well-controlled and well-managed with data safety review boards, multiple studies showing negative results were not needed, he said.
There is no question that replicating studies has value, but in this situation the industry was duplicating harm to patients, as all three studies showed decrements in overall survival.
This problem isn’t limited to multiple myeloma.
With six checkpoint inhibitors on the market, do patients and their doctors really need more of the same? While these drugs are transformative for some, they don’t help the majority of people who take them. What’s more, their use is usually accompanied by harsh side effects. Despite this, the Cancer Research Institute estimates that a whopping 2,250 clinical trials are currently underway for PD-1 or PD-L1 agents — 748 more trials than a little over a year ago.
Is this really the best we can do or strive for? When people enroll in cancer clinical trials, they are placing their lives in our hands. Many have advanced disease and turn to a clinical trial for hope and possible healing. Yet as an industry, we are competing for these patients to test me-too drugs with significant toxicity, sometimes based on marginal preclinical data.
Pazdur said that patients are not a company’s resource. He’s right. They are people who are hoping for a chance at recovery, or at least more time with their families with reasonable quality of life. We should treat patients who volunteer for clinical trials the way we would treat our mothers or husbands or best friends.
Pazdur asked companies to be more efficient by collaborating, sharing data, and conducting platform trials. Some biopharmaceutical companies are trying to do this, but the industry has a long way to go. We should be moving drugs into clinical development only when there’s a strong understanding of disease biology and substantial evidence that a drug has the potential to truly improve lives.
This means rethinking what is an acceptable toxicity profile for a cancer drug and no longer accepting that feeling horribly ill is par for the course for cancer treatments. The drug industry has spent more money to develop more oncology drugs in the last few years than ever before, yet we have not made significant headway in providing broadly effective cancer therapies with limited toxicity. It’s a given that effective oncology treatment will involve combinations of drugs. We need to identify those combinations that offer the appropriate risk for the benefit and allow for a reasonable quality of life.
To develop effective cancer drugs that are well-tolerated, we must slow down and invest the time and dollars at the earliest stages of cancer biology, as well as in preclinical and early-stage clinical trials, ideally leveraging key biomarkers to accurately measure a drug’s effects and identify responders, in order to evaluate if a drug is really worth pushing through late-stage studies into larger populations. Along the way, each company bringing drugs to clinical trials should always be asking: Would I give this drug to a loved one?
By raising the bar, we can give people with cancer new drugs that give them more time with their families and friends without debilitating side effects. We owe it to the millions of people diagnosed with cancer who are looking towards clinical trials as their last hope. And we should accept nothing less.
Pazdur warned that he and the FDA are not pleased with the current state of affairs in the biopharmaceutical industry. We need to take this rebuke to heart, seriously reevaluate our current processes, and once again put patients at the heart of clinical trials.
Gail McIntyre, Ph.D., is the chief scientific officer of Aravive (ARAV), a biotechnology company based in Houston.