ORLANDO, Florida — It's not often that drugs can completely transform the trajectory of a disease — but for chronic myeloid leukemia (CML), that is what tyrosine kinase inhibitors (TKIs) have done. They have changed an invariably lethal disease into a manageable chronic condition.
Before these drugs came along, there were about 20,000 patients with CML in the United States.
Now there are about 112,000 such patients, and that is projected to rise to 180,000 in 2050.
However, the catch is that patients usually stay on the drug indefinitely.
And this is an issue, because the drugs are expensive.
So there was hope that, when the first of these drugs — imatinib (Gleevec, Novartis) — came off patent, generic versions would reduce cost of treatment.
Have those hopes been realized?
Not so much, said an expert discussing the topic here at the recent annual meeting of the American Society of Hematology. But there is now hope from very recent developments, he added.
"TKIs have revolutionized clinical outcomes in CML, and improved life expectancy to almost that of the general population," commented Gary Lyman, MD, MPH, senior lead for healthcare quality and policy within the Hutchinson Institute for Cancer Outcomes Research, Fred Hutchinson Cancer Center, Seattle, Washington.
"The high prices [of TKIs] are almost a scandal — they are exorbitant and put an enormous financial burden on patients and their families and the healthcare system," he said.
"Imatinib could be the quintessential poster child for drug costs escalating out of control," he continued.
"When imatinib entered the marketplace in 2001, it was priced at about $30,000 a year. That remained flat for a while and then rose steeply, even after the patent expired in 2013," he noted. "By 2012, imatinib was priced at $92,000, and then jumped to $132,000 in 2014, and then to $146,000 in 2016 when the generic version became available."
When the first generic versions of imatanib appeared, they were priced not much lower that the patented product, he noted. But there have been some recent reductions in generic imatinib pricing, and these are encouraging. "The hope is that these reductions will be sustained and reduce the financial burden and improve access to these drugs."
Sky-high Cancer Drug Prices
The US has the dubious distinction of having the highest expenditures in healthcare, but ranks far from the top in terms of improvements in life expectancy, explained Lyman. "Part of this is driven by the cancer drug experience, and healthcare costs have risen faster than gross domestic product."
Cost escalation began in the early 2000s, and eventually exceeded the median household income of a typical family. The price tag of new cancer drugs now exceeds $10,000 per month ($120,000 annually), Lyman explained, which is several fold greater than the median household income (around $63,000 in 2018, according to official figures).
"It is a real challenge for patients and families to be able to afford these drugs," he said.
This has been described as 'financial toxicity,' which comes on top of the usual toxicity of cancer treatment, and can limit treatment decisions, access to care, and affect outcomes.
"The cost in this setting matters to patients, but it should matter to us — to payers and to society as a whole," said Lyman.
Generic Products Were Delayed
Imatinib became a best-selling drug for Novartis (with sales of $4.7 billion in 2012), and when the product came off patent (in 2013), the company used pay-for-delay deals to postpose the entry of generic imatinib into the American market from July 2015 until February 2016.
In a pay-for-delay strategy, a patent holder — in this case a pharmaceutical company — agrees to pay a potential competitor who has threatened to enter the market with a generic product. They are often called 'reverse-payment' patent settlements because the payment flows in a direction opposite what is normally expected in patent litigation cases.
Novartis eventually settled a case concerning a generic version of imatinib developed by a subsidiary of Sun Pharmaceuticals Industries. According to the settlement, Sun Pharma's generic version of imatinib was allowed to enter the US market in February 2016 and, because it has first-filer status, it was entitled to 6 months of marketing exclusivity. That meant that no other generic versions of imatinib could be launched in the US until at least August 2016.
Lyman noted that when generic imatanib eventually reached the US market, it was "curious that the generic was almost as expensive as the branded product. This is quite a contrast to other countries."
In 2016, branded imatinib cost $146,000 per year, while the generic version was priced at $140,000.
In Canada, the patented product cost $38,000, whereas the generic was priced between $5000 to $8000; the generic in India runs about $400.
"We have a clear disconnect between pricing in the US and what's available in the rest of the world," Lyman said.
Also affecting the cost of care in CML was the introduction of second and third generation TKIs in 2006, which led to a decrease in the use of imatinib.
"It is important to emphasize that while the second and third generation TKIs may produce a deeper molecular response and perhaps a more durable response, no clinical trial has shown an advantage in terms of overall survival and progression-free survival," he emphasized. "That adds to the complexity of the clinical decision of what to use up front."
Generic Price Dropping?
There are several generic imatanib products on the US market, and there has been a decrease in the use of the branded product, Lyman noted.
But will these generic products push down the cost of drug therapy?
"I can be a skeptic and say that the generic prices competition may not be enough to reduce the price of these drugs," said Lyman.
"On the other hand, you can be an optimist and see the glass as half full," he said. "The day is early, the generic imatinibs have only been available for a short time, and challenges aside, maybe it's just delaying or slowing price competition. It may just be too early to see the results of the 11 competitors."
Recent Decrease in Generic Imatinib Prices
Over the past year, there has been a dramatic decrease in the price of generic imatinib in the US, Lyman added. "And this brings me to be somewhat optimistic."
Approached for comment, Stacie B. Dusetzina, PhD, associate professor of health policy and associate professor of cancer research at Vanderbilt University School of Medicine in Nashville, Tennessee, was cautiously optimistic, noting that prices of generic products have very recently fallen.
Last year, Dusetzina and coauthor Ashley L. Cole, University of North Carolina, Chapel Hill, published a study (Health Aff. 2018;37:738-742) that looked at the pricing and use of imatinib in CML. They found the price of the generic version had decreased by only 10% in the 20-month period following its introduction (in February 2016) to the marketplace.
"In our article, we looked at the situation a year and half in (in August 2017), and there were only three manufacturers making generic imatinib," Dusetzina told Medscape Medical News. "We had a general sense that we needed four to make the price really competitive."
Right after their article came out, a fourth company began making imatinib and the prices went down, she noted.
In early 2018, the team used online resources to look at cash prices being offered at various pharmacies. They found that the average price for imatinib at the beginning of 2018 was about $2000 for a 30-day supply, whereas through September 2017, the price was about four times higher (roughly $8000).
"But price decreases can take a long time before it is reflected in the health insurance data," Dusetzina explained. "In the last quarter of 2018, the average bill for imatinib in Medicare Part D claims was $4800, which is a substantial decrease from previous amounts."
With more competition now, the price should drop even lower. Coupons offered through places like GoodRx will allow patients to purchase a month's supply of the drug for a few hundred dollars. The lowest price was at Costco, where a 30-day supply of 400 mg tablets sold for $245.74, which is 97% off the average retail price of $11,475.
Dusetzina emphasized that these very low prices are for people willing to pay cash, but all things considered, paying cash could even be less expensive than out of pocket copays and coinsurance. Medicare requires 25% coinsurance, and as imatinib is in a high tier, the out-of-pocket burden can be quite high.
Newer Drugs in Same Class
However, another issue is the growing use of second- and third-generation TKIs as frontline therapy, Dusetzina said. During the research period of her study (2016-2017), there were large shifts in prescribing frontline therapy. Prior to the release of generics, most patients (75%) diagnosed with CML and prescribed a TKI received brand-name imatinib in 2010. Five years later, less than half (40%) were on brand-name imatinib; the remainder received the newer second-generation agents. By 2017, generic imatinib represented only 28% of prescriptions for newly diagnosed patients.
"Even if patients are treatment naïve, providers are not starting patients with imatinib," she said. "This means that patients that are being started on something that isn't necessary."
There may be several reasons for this, including the following: Until very recently, the cost of imatinib hadn't shown any real decline. The branded newer products also offer rebates and other incentives to offset costs. "So it may be that all were equally expensive," she said. "But now that we are seeing the price come down, providers and insurers may need to re-evaluate the treatment choice."
Lyman has received research funding from Amgen. Dusetzina has received funding for related projects from the Laura and John Arnold Foundation, the Leukemia and Lymphoma Society, and the Commonwealth Fund.
American Society of Hematology (ASH) 2019. Presented December 7, 2019.
Medscape Medical News © 2019
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