In 2004, Gilead Sciences decided to discontinue development of new HIV drugs.of Public explanation It was not sufficiently different from existing treatments to justify further development.
But in private, something else was happening.Gilead had made a plan A trove of internal documents released in a lawsuit against the company reveals that executives had reason to believe that new drugs might be safer for patients, but delayed the launch of new drugs to maximize profits.
Gilead, one of the world’s largest pharmaceutical companies, appears to be employing a well-worn industry tactic of using the US patent system to protect its profitable monopoly on best-selling drugs.
At the time, Gilead had already developed two blockbuster HIV treatments, both backed by a class of drugs called tenofovir. These first treatments are set to lose patent protection in 2017, at which point competitors will be free to introduce cheaper alternatives.
A promising drug in early trials at the time was an updated version of tenofovir.Gilead executives said the company Possibly less toxic Internal memos unearthed by a lawyer suing Gilead on behalf of the patient say it’s hurting the patient’s kidneys and bones more than previous iterations.
Despite these possible benefits, executives concluded that the new version risked competing with the company’s existing patent-protected formulations. By delaying the launch of a new product until just before an existing patent expires, the company could significantly extend the patent protection period for at least one HIV drug.
A “patent extension strategy” repeatedly mentioned in Gilead’s documents will allow the company to keep the price of its tenofovir-based drug high. Gilead may switch patients to its new drug just before cheaper generics hit the market. By putting tenofovir on track to remain a money-making giant for decades, the strategy was potentially worth billions of dollars.
Gilead finally introduced a version of this new treatment in 2015, nearly a decade after it might have been available had it not paused development in 2004. The patent is now extended. at least until 2031.
The delayed launch of the new treatment is now the subject of state and federal lawsuits, with nearly 26,000 patients who were taking Gilead’s older HIV drugs alleging that Gilead unnecessarily exposed them to kidney and bone problems.
Gilead attorneys said in court filings that the allegations were without merit. They denied that the company had halted development of the drug to increase profits. They cited an internal memo from 2004 that estimated Gilead would increase revenue by $1 billion over six years if it released a new version in 2008.
“If Gilead was motivated solely by profit, as plaintiffs allege, the logical decision would have been to expedite the development of the new version,” the attorneys write.
Gilead’s top attorney, Deborah Telman, said in a statement that the company’s “research and development decisions have been and continue to be focused on delivering safe and effective medicines to prescribers and users.”
Expensive Gilead drugs, including the new generation of tenofovir, now account for half of the HIV treatment and prevention market, according to industry data provider IQVIA. One of his widely used products, Descovy, has a list price of $26,000 per year. Generic versions of its off-patent predecessor, Truvada, now cost less than $400 a year.
If Gilead had pursued development of this new drug in 2004, its patent would have expired by now or soon.
“We should all take a step back and ask ourselves: How did you allow this to happen?” said James Clenstein, a longtime AIDS activist who advised the lawyers in the Gilead case. “This is what happens when a company intentionally delays the development of an HIV drug for proprietary purposes,” he added.
Gilead’s apparent maneuvers with tenofovir are so common in the pharmaceutical industry that they are called product hopping. Companies survive drug monopolies and, just before generic competition arrives, switch, or “hop,” patients to more recently patented versions of drugs in order to extend the monopoly.
Pharmaceutical maker Merck, for example, is developing an injectable version of its blockbuster cancer drug Keytruda that could bolster revenue streams for the company for years after the injectable version of the drug faces initial competition in 2028. said yes).
Christopher Morten, a pharmaceutical patent law expert at Columbia University, said the Gilead case shows how the US patent system creates incentives for companies to slow down innovation.
“There’s something seriously wrong here,” said Morten, who in 2019 provided free legal services to HIV advocacy groups. We’re screwed challenged Gilead’s efforts to extend the term of its patents; “The patent system has actually encouraged Gilead to delay the development and launch of new products.”
Central Florida resident David Swisher is one of the plaintiffs in federal lawsuit against Gilead. He took Truvada for 12 years from 2004 and developed kidney disease and osteoporosis. Four years ago, when he was 62, he said doctors told him he had the bones of a 90-year-old woman.
It wasn’t until 2016, when Descoby finally hit the market, that Swisher stopped using Truvada. By then, he was too ill to work and quit his job as an airline flight manager, he said.
“I feel like all that time has been taken from me,” he said.
First synthesized by then-Czechoslovak researchers in the 1980s, tenofovir was the starting point for Gilead’s dominance in the HIV treatment and prevention market.
In 2001, the Food and Drug Administration first approved Gilead’s first tenofovir-containing product. Four more follow. These drugs prevent replication of HIV, the virus that causes AIDS.
They are credited with revolutionizing the fight against AIDS and saving millions of lives around the world. The drug is now used not only as a treatment, but also as a prophylaxis in people at risk of infection.
However, a small percentage of patients taking the drug for HIV treatment developed kidney and bone problems. It has been found to be particularly dangerous when used in combination with booster drugs to increase its effectiveness, and although it was once common, it has since fallen out of use.of world health organization and the United States National Institutes of Health Avoid using original tenofovir in people with fragile bones or kidney disease.
Newer versions do not have these problems, but may cause weight gain and elevated cholesterol levels.For most people, according to experts, his two tenofovir-based drugs, the first TDFcalled the second TAF — offer roughly equal risks and benefits.
Company records from the early 2000s show that Gilead executives sometimes struggled with whether to rush new drugs to market. In some respects, the document considers his two repeat doses of tenofovir to be similar from a safety standpoint.
But other notes indicate that the company believed the updated formula was less toxic, based on research in labs and animals. These studies showed that the new formulation has two advantages that can reduce side effects. This means that tenofovir is much better than the original at getting it to target cells, and significantly less tenofovir leaks into the bloodstream and reaches the kidneys and bones. and it may be given in lower doses.
A 2002 internal memo stated that the new version “has an improved side-effect profile and may reduce drug-related toxicity.”
The same year, the first human clinical trials of the new version began. A Gilead employee planned a development schedule for his 2006 launch of the new formulation.
But in 2003, Gilead executives began to be reluctant to rush the business. They were concerned that doing so would “eventually cannibalize” the growing market for the older version of tenofovir, according to the paper. Internal meeting minutes. Norbert Bischofberger, Gilead’s head of research at the time, instructed in-house analysts to explore the potential of the new formulation as an intellectual property “expansion strategy,” according to an email from a colleague.
As a result of that analysis, Notes from September 2003 The document described how Gilead would develop a new formulation to “replace” the original and “time it to launch in 2015.” In a best-case scenario, the company’s strategy would see him generate more than $1 billion in annual profits between 2018 and his 2020, according to company analysts’ calculations.
Gilead revived the new formulation in 2010 and put it on track for release in 2015. Gilead’s president and future chief executive, John Milligan, told investors that this would be a “friendly, gentler version” of tenofovir.
After obtaining regulatory approval, the company embarked on a successful marketing campaign targeting physicians. promotion The new version is safer for kidneys and bones than the original.
By 2021, nearly half a million people with HIV in the United States will be taking Gilead products containing the new version of tenofovir, according to market research firm Ipsos.
Susan C. Beachy Contributed to research.
