Imatinib

We've gone through everything else.

After Preston was discharged, Mooney picked up his prescription, a pill called Imatinib, an oral targeted therapy that she was to administer regularly.

That winter, she periodically celebrated in a family group chat that Preston's labs were normalizing.

Several months after the diagnosis, though, Preston's condition began worsening.

That means we had a long follow-up of some cohorts of patients and have seen that the immediate side effect rate and also the long-term side effect rate is lower than what we had available with the ATP-competing drugs.

And this was confirmed in the Assembl trial, third line and later, against the Bosutinib, and also in the first-line trials now compared to Imatinib and second-generation drugs.

That means the overall spectrum of immediate side effects is lower.

What we see, what is left are some cytopenias in the beginning of treatment.

but also other kinases.

Imatinib and nilotinib are more specific, but we have now with asiminib a drug available which is very specific to BCR-ABL based on a different mode of action.

That means we don't have an off-target inhibition.

And the off-target inhibition may be relevant for side effects, because if other kinases are inhibited, this can produce side effects.

And therefore, we need the transcript type at diagnosis.

So with second generation, there is more overlap in the false plot, but overall a clear advantage for Aciminib.

So now the deep molecular responses, that means the trigger for discontinuation on the right, MR4.5, clear advantage of Aciminib over Imatinib, and also an advantage of Aciminib over the second generation drugs.

That means This is after three years.

There is so much to do for our patients and, as you say, this year we celebrate 25 years of imatinib.

This is a huge milestone.

Imatinib revolutionized how we treat patients because it's the fourth example of targeted therapy that we can apply to patients.

But since then, A lot has been developed for CML patients, and there was a dramatic change with the introduction of imatinib, but not every patient had the response that we want.

So you need to know that not all patients respond to therapy in the same way.

Luckily, the Centers for Medicare and Medicaid Services, otherwise known as CMS, they have a tremendous amount of data available on their website where you can go in and see what states like Ohio or any other state in the country are being charged for medicines.

We looked at a drug called Gleevec, which at the time was a true miracle drug and still is today.

It's a drug that treats leukemia patients, and the patients would have to take those drugs once daily for the rest of their lives.

The brand drug was $330 a pill, so you can run the numbers and say, wow, that's going to be very expensive for a very sick patient who likely is incapable of working.

But expensive drugs are supposed to eventually give way to cheap generic drugs because the recipe, if you will, for that brand drug gets released after the patent expires, and then everybody can compete to lower the cost of that drug.

And that's exactly what happened with generic Gleevec years ago, where the drug went from $330 a pill to less than $5 a pill.

But lo and behold, Ohio Medicaid and other employers across the country and sick patients we're still paying the old stale rate.

So the question is, what is going on? If the underlying cost of the drug is going down, how are those savings not being passed on to the consumers? This is where pharmacy benefit managers or PBMs enter the equation to explain what is otherwise unexplainable.

Um, Herceptin is an example with HER2.

Gleevec in the myelogenous leukemias.

Remarkable success.

And there will be a role for targeted therapies going forward.

It varies what the wholesale acquisition cost is, but let's just say your primary wholesaler sells it to you for $200 and you realize that Cost Plus Drug sells it for $25 and you wanna buy it through Cost Plus marketplace.

Benjamin Jolley in episode 422 references the classic imatinib example directly.

The figures that he discusses are that branded Gleevec costs $27,000 a month, or that's what it used to cost.

Generic imatinib, which is the generic for Gleevec, through a traditional PBM/insurance channel, at least at the time when I interviewed Benjamin Jolley, was $9,000 a month, which the PBMs would tout as massive savings.

Like, look, you're saving $18,000 a month off the original branded Gleevec.

Now, Mark Cuban's Cost Plus Drugs cash price is $25 a month, not $9,000 a month.

$25.

Let's focus on finding- Ways to fix these genes, right? So a totally new paradigm.

And then what you say is that, well, the first few treatments, so we treat-- developed this one called imatinib, which is also called Gleevec, which is for a type of leukemia called CML.

Very rare cancer, but, uh, unbelievably good.

Like, the treatment just sort of revolutionized the treatment of CML.