Ibrutinib, idelalisib, GA-101 (aka obinatuzumab - if I got that right), ABT-199, etc. The tidal wave of new drugs is exciting because we will soon be treating the disease with therapies that are very effective and lack many of the side effects of chemotherapy. These are some of the exciting new drugs coming soon for patients with CLL and NHL. Unfortunately they will probably also break the bank. I bet that ibrutinib costs about $150k per year... that is my prediction.
CML is a leukemia that has a lot in common with CLL. It is a slow cancer that affects about 10k new patients per year. Historically (before the year 2000) patients lived a number of years (3-5) with the disease and put up with a bunch of lousy chemotherapy drugs that didn't do much. Eventually the disease took on a nasty personality (like richter's transformation) and the patient died of "blast crisis."
That all changed in 2000 when a new "wonder pill" called Gleevec made the disease vanish from patients blood. A single, once a day medication literally changed overnight what it meant to hvae the diagnosis of CML. Newer, more sensitive molecular tests were required to even detect the disease that could no longer be seen by standard tests like, "cytogenetics." Sounds familiar right?
Gleevec cost about $40k/year when it first came out (we can talk about how much that price has risen later). While that number seems extremely high - it is inexpensive compared to many of the new drugs for cancer.
Why so high?
I have a prior post about why drug development takes so long. It might be a good read for starters because it can help explain why the process is long and expensive. A landmark study from 2002 estimated that the total research and development costs of a new drug was about $800,000,000 (eight hundred million dollars). That is the price for a drug that actually gets approved. Then you need to take into account all of the drug failures. There are a ton of drugs that get made that never even enter human clinical trials. Of the ones that enter phase 1 testing, somewhere between 5-20% will ever see a successful phase 3 trial and get approved.
Join the high cost of drug development and the high rate of failure and you have a formula for expensive drugs - but that still misses one critical ingredient - what is the frequency of the disease? If you are making a new drug for cholesterol, you can treat just about everyone in America. If you are making a drug for angioimmunoblastic T cell lymphoma - you have to recoup your costs on the backs of the 1000 patients per year that get the diagnosis. The formula goes something like: (drug development costs divided by number of patients = drug price).
One irony is that the number of new patients diagnosed with CML per year hasn't changed, now that patients are living much longer, CML has actually become quite common. Every oncologist probably has a handful of CML patients in their clinic because instead of living 3-5 years, they now all live almost normal lives.
Ok, I think most readers at this point can agree that drugs for CLL and NHL will be expensive. Many readers will agree that the drug developers should be rewarded for taking enormous risk and bringing new effective drugs to patients with cancer. Some would say that we should just have government funded research and that would make drugs more affordable. Unfortunately, I've seen both government supported research and pharma research up close. If we relied on government based research to bring new drugs, I think we would still be stuck with chlorambucil.
But at what point does a drug price go from being a fair reward for innovation to profiteering off vulnerable cancer patients? In the last ten years we have seen remarkable breakthroughs in cancer treatment but it doesn't always seem like price and effectiveness are totally linked. Some new drugs are small incremental improvements while others are truly revolutionary. What is odd is that the difference between a "single" and a "homerun" have no impact on cost. Any new cancer drug is more than $100k/year. Academic thought leaders have taken note and for the first time we are seeing organized pushback.
One clue to me that we are in an era of profiteering is that the price of a new drug seems more linked to what the price of the most recently approved drug was rather than how effective the new drug is. In the case of Zaltrap - a newly approved drug for colon cancer that didn't move the needle too far in terms of effectiveness (ie. new mechanism but not a whole lot more effective) the price was right on mark with other recently approved drugs (over 100k per year). Fortunately the organized rebellion of academic thought leaders has resulted in a decreased price for this drug.
I believe that market forces are able to result in fair prices in most situations. The problem with medical care is that it isn't a normal market. When you go to buy a car, you figure out what something is worth and you decide if the dealer is selling it for a fair price. If not, you walk away. In medicine though, how do you put a value on keeping your hair? Staying at your job instead of taking sick leave? How do you decide the value of an additional year of life. Is that the same for a 25 year old as an 85 year old? Value determinations are difficult. Furthermore, in medicine you may have your co-payments but chances are some anonymous third party is paying the lion share of the cost. Who wouldn't want the latest and greatest if they don't have to foot the bill. Add to that the lack of choice. You can't just go down the street to a different car dealer when it comes to picking a therapy in lymphoma. Without market forces, drug prices get all out of whack.
If we come back to the price of Gleevec it is interesting that the price has risen over the years. Two newer drugs came along (sprycel and tasigna) that had prices set around the going rate when those drugs were approved. Oddly enough, Gleevec rose too. The drug didn't get better, it's peers got more expensive and they were able to rise closer to their peer group. This has drawn the focused criticism of many CML docs as well as a rebuttal from the maker of two of these drugs. It will be interesting to watch what happens to all three drugs when Gleevec goes generic soon. A generic drug can sometimes drop in price by 90% overnight. Sprycel and tasigna are better than Gleevec but I bet the price of all three drop considerably.
I think most patients who see these prices for their care experience some disbelief and anger. It is hard to know where to place that anger and sometimes that falls upon the drug companies, sometimes the insurance companies, and sometimes even the doctors caring for the patient. I can tell you as a docs are not the ones making much money - in fact some docs are closing up shop or refusing to see Medicare patients because they can't deal with the costs anymore. Any simple answer probably misses a lot of complexity.
It is clear to me that the current trajectory is unsustainable. I watched in amazement as Peter Hillman gave an analysis of the impact of new CLL drugs on the overall spending of the British Health Service. New CLL drugs alone could tank the British cancer funding system. I credit the British for having a system that also takes into account the cost of drug in determining coverage. In the US it is strictly about safety and efficacy. Drug prices are not a factor in determining approval.
I am not sure I can offer solutions without getting too political. We all want new drugs but in a broken marketplace you cannot expect "fair prices" to sort themselves out. I'm not even sure that a "single payor system" could afford the innovation we are seeing now. I think the best thing we can all do right now is get involved in clinical trials so that there are a bunch of new BTK or PI3K inhibitors out there to restore some degree of choice.
