Researchers said only half of the cancer drugs approved by European regulators in the past few years have shown to help patients. Many of the drugs were approved without any conclusive evidence of their efficacy.
The new study by scientists in Britain and Latvia showed that the European Medicines Agency (EMA) approved 39 new cancer drugs between 2009 and 2013 without evidence that they worked. A total of 68 cancer drugs were given a nod by the European drug regulator during the period.
“We were quite surprised about the high proportion of drugs entering the market without evidence,” said Huseyin Naci, of the London School of Economics, one of the study’s authors.
The researchers found that only about half of the approved drugs significantly improved patient survival or their quality of life. The efficacies of the remaining drugs were “uncertain,” they said. “This situation has negative implications for patients and public health,” they concluded in the study published online on Thursday (October 5, 2017) in The BMJ medical journal.
“When expensive drugs that lack clinically meaningful benefits are approved and paid for within publicly funded healthcare systems, individual patients can be harmed, important societal resources wasted, and the delivery of equitable and affordable care undermined,” the authors said.
The EMA said it “has discussed the evidence underpinning cancer medicines widely and welcomes further debate on this.”
Naci said the existing drug-approval process, which does not require drugmakers to prove that their treatments improve or extend life, offers little incentive to them to produce more rigorous proof that their drugs work.
The study found that even among the 23 drugs that improved survival, 11 failed to meet the modest definition of “clinically meaningful benefit” set by the European Society of Medical Oncology.
If you’re like me, hardly a week goes by these days where you don’t wake up in the morning, fire up the Internet and are confronted with some mind-boggling account of another “cure” for a type of cancer that not that long ago was an early and certain death sentence.
Terms like PARP inhibitors, CAR-T cell therapies, checkpoint inhibitors; names like Opdivo, Keytruda, Kymriah and Gleevec, just to name a few. And are they expensive? Novartis’s Kymriah has a cost of $475,000. And that’s just a mid-range price among the entire bunch.
Don’t get me wrong. The eruption of new cancer drugs that’s occurred over the past decade includes major superstars that have registered some eye-watering results in clinical trials. But I was surprised to find out that researchers at prestigious King’s College London and the London School of Economics decided to hit the pause button and examine 68 cancer indications approved in Europe over a 5-year period through 2013, they found that many were sanctioned on only tenuous data resulting from unreliable trial designs. At least 10 of these approvals have never demonstrated any real benefit for patients.
Regulators and agencies like cost watchdog NICE, which often refuse to cover high-priced cancer drugs, are slammed by pharma industry critics who say that the trend of fast-tracking oncology therapies has put a long lineup of drugs into routine use, even though the companies haven’t supplied solid evidence of efficacy four or more years later.
Sixty-eight cancer drug indications won European approval between 2009 and 2013–but most of them got the green light without showing they could extend or improve life. Fifty-seven percent of indications approved during that period hit the market based on endpoints other than overall survival or improved quality of life. Instead, they won approval thru “surrogate” endpoints such as tumor shrinkage or progression-free survival.
And after a median of five years on the market, only eight drug indications had managed to post data showing a survival or quality of life benefit.
Lastly, in many situations where new meds did show benefits over existing therapies, those benefits were marginal. The way the researchers see it, that’s not acceptable considering the products’ high prices, says FiercePharma.
The jarring results come not long after two confirmatory trials failed to show that high-profile, immuno-oncology medicines could improve overall survival. Roche Holding AG’s Tecentriq was the first to bomb, failing to extend survival among bladder cancer patients, and Merck & Co.’s Keytruda followed with a washout in head and neck cancer.
According to Vinay Prasad, MD, an assistant professor at Oregon Health & Sciences University, most cancer drugs, which cost about $100,000 per year of treatment, are being approved based on “flimsy or untested” initial measures and declared that the regulatory system was “broken.”
“The expense and toxicity of cancer drugs means we have an obligation to expose patients to treatment only when they can reasonably expect an improvement in survival or quality of life,” Prasad said.
He cited another study, published in 2015, that showed most cancer drugs approved by the US Food and Drug Administration between 2008 and 2012, similarly did not show any evidence that they helped a patient’s life.
Taken together, the foregoing facts paint a grim picture. In sum, although we are approving cancer drugs at a rapid pace, few come to market with good evidence that they improve patient-centered outcomes.
If they do, they often offer marginal benefits that may be lost in the heterogeneous patients of the real world. Most approvals of cancer drugs are based on flimsy or untested surrogate endpoints, and post marketing studies rarely validate the efficacy and safety of these drugs on patient-centered endpoints.
I recently wrote that we face an intractable dilemma in that society wants personalized medicine, yet who is going to pay for the cost of it? Insurance providers will not pay for CAR-T therapy because it presently is unproven by regulatory standards as well as their own company standards; the side effect profile is risky even though it can be managed, and it is very expensive. Today, most insurance companies will only pay for the standard treatments and it’s only when all other therapies fail will they consider cellular therapy.
The actual answer to who gets access to these extremely costly “wonder drugs” relies on the payer. That’s because an insurance company will not pay for a new therapy unless it is proven that CAR-T therapy, for example, works and is a cure, by their standards not just the FDA’s, it is safe, and it saves the insurance company money.
But to ascertain this, economic data must be collected for a predetermined period not just to demonstrate these factors, but also that the med saves the company money compared to “standard of care” treatment. This can be generic versions of the drug or biosimilar of a biologic drug.
We need to embrace the notion of treating the right patient with the right drug, with the freedom of advance technology being covered by insurance, and encourage the principle that not every disease needs to be treated with the latest “breakthrough.” Especially where we don’t know if it actually works.