This news release by the Dana-Farber Cancer Institute is a teaser on a potential new drug target for sufferers of a blood cancer called chronic myelogenous leukemia, or CML, which affects 30,000 Americans a year.
The release spends a good amount of space explaining the condition and problems with a standard treatment — a drug called Gleevec (a brand-name version of the drug imatinib) — and how up to 90% of patients with the disease face a lifetime of medication that may eventually stop working. It also does a nice job explaining a biological pathway that helps drive CML and why it might be a mechanism to target in the future, specifically Ezh2 inhibitors.
However, the study was done in mice — not people. The release belatedly points this out in the final third of the text — but we would have liked to see it more prominently mentioned. The reason: The relevance may not transfer to people with CML. That’s also why we think the repeated use of the word “cure” and the possibility of shorter treatment in the headline is overstating and misleading. One glaring omission was that of price. The only allusion to price in the news release is an aside in the closing line noting shorter treatment times translate into cost savings. We’re also given no rough treatment cost estimates for an unnamed Ezh2 inhibitor made by Epizyme that’s mentioned in the release.
Chronic myelogenous leukemia (CML) develops in bone marrow and affects myeloid cells. Those cells typically mature into platelets or red blood cells, but genetic and other abnormalities can lead them to mature into defunct granulocyte cells, i.e. leukemia. CML patients experience a gradual though sometimes rapid build-up of leukemia in their bones and then in their spleen, crowding out healthy cells over time. This drives symptoms that may include frequent infections (due to immune system weakening), fatigue (fewer red blood cells), and easy bleeding (fewer platelets).
CML affects about 30,000 people each year and about 1.2 million to 1.5 million people worldwide, most of them middle-aged adults (though there are a few children). While patients who seek the standard of treatment — imatinib (marketed as Gleevec and Glivec) — receive it “indefinitely,” the median survival is between 5-6 years, since leukemia cells can build up resistance to imatinib-like drugs. In fact, about 80-90% of patients can’t clear all of their leukemia cells and stay on permanent drugs.
By increasing the number of CML patients who can drive their cancer into remission, suffering could be dramatically reduced — as would the cost of their treatment. As teased by this release, Ezh2 inhibitors may (or may not) help CML patients. Clinical trials would have to determine if that hypothesis pans out.
Oddly, the release includes a quote from the study’s leader about how “the cost savings of such an approach could … be significant” — yet treatment cost estimates are completely absent in the release.
Cost deserved more than the nod given in this release. The release mentions the treatment will be a “Gleevec-like” drug so it’s notable that the costs may also be “Gleevec-like” to start. A 2016 Washington Post article noted that the wholesale cost of Gleevec had risen from $26,400 to $120,000 annually over the 15 years it has been on the market. Even with insurance, a patient might have paid $500-$800 month out-of-pocket for the drug, the Washington Post found. The introduction of generics after the patent on Gleevec expires this year will bring the cost down dramatically.
In the chronic phase of the disease, where remission isn’t likely, the average cost for brand-name imatinib per year is $79,000 a year, or $92,000 by a more recent estimate. A large group of physicians wrote in a 2013 cost analysis study in the journal Blood: “We believe the unsustainable drug prices in CML and cancer may be causing harm to patients.” Fortunately, a generic drug should cost $46,000 a year as Gleevec loses patent exclusivity in 2016, according to a recent study in the Journal of the National Cancer Institute.
But that’s just imatinib. Although the release mentions an Epizyme-made Ezh2 inhibitor drug in an unrelated Phase 1 clinical trial, it doesn’t name it.
The release makes clear that its discovery of a potential weak point in a frustrating form of leukemia has the potential to push CML patients into remission. But it doesn’t quantify those results in any way. Even more importantly, the release drags its feet when disclosing that the research was performed in animal subjects. It remains to be seen if the treatment would have similar benefits for people. And that result could be many years down the road.
Side effects are mentioned for imatinib, but never detailed. And this is a major oversight that would have benefited the crux of the release (i.e. a need for alternatives to imatinib-like drugs). One 2010 study assessed a flotilla of side effects, including muscle cramps, nausea, diarrhea, headaches, abdominal pain, joint pain, and more in greater than 10% of patients who take it for CML. But it also notes a rare few can be “sinister” in less than 1% of patients: heart damage, kidney failure, muscle degeneration, secondary cancers, and even cerebellar edema, which can cause fainting, seizures, and even put someone into a coma.
The side-effects of Ezh2 inhibitors also aren’t noted since it seems the most promising one is still in clinical trials. Since the new drug hasn’t been tested in humans there is really no way to gauge side effects but all cancer drugs have them, often very serious ones as noted above.
We’re told that when gene-editing techniques turned off Ezh2 in mice with CML, it prevented their leukemia cells from progressing, “halting the disease at its source.” But it’s one thing to go from a genetically engineered mouse to a human patient, let alone targeting that person’s disease with a fairly experimental drug.
There are so many studies in mice that don’t pan out in humans. This release appears to be putting the cart before the horse.
We don’t see anything that would scare a reader.
We’re told the pharmaceutical company Epizyme opened a phase 1 clinical trial at Dana-Farber/Boston Children’s hospital. We’re also told an NIH grant and Hyundai Hope on Wheels is funding the study. The release also notes one of the authors on the study is an employee of Novartis Pharmaceuticals — which owns the (soon-to-expire) patent for Gleevec, also called Glivec.
Aside from the current standard of care — imatinib-like drugs — the release only vaguely references “second- and third-line targeted therapies” that “can often return the disease to remission,” yet doesn’t name them.
The release notes imatinib-like drugs are the standard of care for CML patients, implying a diagnosis would grant access to the drugs by prescription. Though it doesn’t name the potential Ezh2 inhibitor drug, the release does note it’s part of a Phase 1 trial, as well as other clinical trials — implying it’s not readily available. A lack of absolute clarity here isn’t helpful to readers, but there’s enough to mark this satisfactory. A statement that clarified that it would likely be years before testing in humans would be complete would have been appropriate here.
The release does a decent job of teeing up the connection between the leukemia cells that drive CML and a biological pathway that an existing drug might be able to target.
The repeated use of the term “cure” — including in the headline — when only preliminary animal data is being presented — is unjustifiable.