In 2004, Gilead Sciences decided to stop working on a new HIV drug. public explanation was that it was not sufficiently different from existing treatments to warrant further development.
However, in private, something else was going on. Gilead had made a plan According to internal documents made public in litigation against the company, the release of the new drug was delayed in order to maximize profits, even though executives had reason to believe it could be safe for patients.
Gilead, one of the world’s largest drugmakers, appears to be adopting a well-worn industry strategy: betting on the US patent system to protect lucrative monopolies on top-selling drugs.
At the time, Gilead already had a pair of blockbuster HIV treatments, both based on a version of the drug called tenofovir. The first of these treatments is set to lose patent protection in 2017, at which point competitors will be free to offer cheaper alternatives.
The promising drug in the early stages of the trial was an updated version of tenofovir. Gilead executives knew that he had likely to be less toxic Patients’ kidneys and bones were more affected than the previous iteration, according to internal memos discovered by lawyers suing Gilead on behalf of patients.
Despite those potential benefits, executives concluded that the new version risks competing with the company’s existing, patent-protected formulations. If they delay the release of the new product until shortly before the existing patent expires, the company can substantially extend the period of time in which at least one HIV treatment remains protected by the patent.
The “patent extension strategy,” as it is referred to repeatedly in Gilead documents, will allow the company to keep prices high for its tenofovir-based drugs. Gilead can convert patients to its new drug just before cheaper generics hit the market. The strategy was potentially worth billions of dollars, putting tenofovir on track to be a money-making juggernaut for decades.
Gilead introduced a version of the new treatment in 2015, nearly a decade after it would have been available if the company had not stopped development in 2004. Its Patents Are Now Extended at least until 2031,
The delayed release of the new treatment is now the subject of state and federal lawsuits in which nearly 26,000 patients taking Gilead’s older HIV drugs claim the company unnecessarily exposed them to kidney and bone problems.
In court filings, Gilead’s lawyers said the allegations were baseless. He denied that the company stopped drug development to increase profits. He cited a 2004 internal memo that estimated that Gilead could increase its revenue by $1 billion over six years if it released the new version in 2008.
“If Gilead was motivated only by profit, as Plaintiffs argue, the logical decision would have been to accelerate development of the new version,” the lawyers wrote.
Gilead’s top lawyer, Deborah Tellman, said in a statement that the company’s “research and development decisions have always been and will continue to be guided by our focus on providing safe and effective medicines for the people who prescribe and use them.”
Today, a generation of expensive Gilead drugs containing a new version of tenofovir accounts for half of the market for HIV treatment and prevention, according to IQVIA, an industry data provider. One widely used product, Descovy, has a sticker price of $26,000 annually. Its predecessor, Truvada’s generic version, which has expired off-patent, now costs less than $400 a year.
If Gilead had gone ahead with development of an updated version of the drug in 2004, its patents would either have expired by now or would have expired sooner.
“We should all take a step back and ask: How did we let this happen?” James Krellenstein, a longtime AIDS activist, has advised the lawyers suing Gilead. He added, “This is what happens when a company intentionally delays the development of an HIV drug for monopolistic purposes.”
Gilead’s apparent maneuvering with tenofovir is so common in the pharmaceutical industry that it has a name: product hopping. Companies end their monopoly on a drug and then, shortly before generic competition arrives, they switch patients to – or “hop” – the recently patented version of the drug in order to prolong the monopoly.
For example, drugmaker Merck is developing a version of its blockbuster cancer drug Keytruda that can be injected under the skin, and an infused version of the drug is expected to boost the company’s revenue stream for years after first facing competition from other companies in 2028. (Merc spokeswoman Julie Cunningham denied that it engaged in product hopping and said the new version is “a new innovation aimed at providing a greater level of convenience for patients and their families.”)
Christopher Morton, an expert in pharmaceutical patent law at Columbia University, said the Gilead case shows how the US patent system incentivizes companies to slow innovation.
“Something has gone terribly wrong here,” said Mr. Morton, who provides pro bono legal services to an HIV advocacy group, in 2019. fail challenged Gilead’s efforts to extend the term of its patent. “The patent system actually encouraged Gilead to delay the development and launch of a new product.”
David Swisher, who lives in Central Florida, is one of the plaintiffs suing Gilead in federal court. He took Truvada for 12 years starting in 2004 and got kidney disease and osteoporosis. Four years ago, when he was 62, he said, his doctor told him he had “the bones of a 90-year-old woman.”
It wasn’t until 2016, when Descovy was finally on the market, that Mr. Swisher discontinued Truvada, which he believed was causing him losses. By that time, he said, he had become too ill to work and had retired from his job as an airline operations manager.
“I feel like that whole time was taken away from me,” he said.
First synthesized in the 1980s by researchers in then Czechoslovakia, tenofovir was the springboard for Gilead’s dominance of the market for treating and preventing HIV.
In 2001, the Food and Drug Administration approved a product containing the first version of Gilead’s tenofovir for the first time. Four more would follow. The drugs block the replication of HIV, the virus that causes AIDS.
He became a game-changer in the fight against AIDS, credited with saving millions of lives worldwide. Medicines began to be used not only as a treatment, but also as a prophylactic for those at risk of becoming infected.
But kidney and bone problems developed in a small percentage of patients taking the drug to treat HIV. It proved particularly risky when combined with booster drugs to increase its effectiveness – a practice that was once common but has since become popular. World Health Organization and America National Institutes of Health Discourage use of the original version of tenofovir in people with brittle bones or kidney disease.
The newer version doesn’t cause those problems, but it can cause weight gain and increased cholesterol levels. For most people, experts say, two tenofovir-based drugs — the first known as tdfthe other called taf – Offer roughly equal risks and benefits.
Internal company records from the early 2000s show that Gilead executives at times struggled with whether to rush a new formulation to market. At some points, the document describes the two iterations of tenofovir as identical from a safety perspective.
But other memos indicated that the company believed the updated formula was less toxic, based on studies conducted in laboratories and on animals. Those studies found that the new formulation has two advantages that may reduce side effects. It was much better than the original at delivering tenofovir to its target cells, meaning that much less of it leaked into the bloodstream, where it could travel to the kidneys and bones. And it can be given in lower doses.
“The new version may translate into a better side effect profile and less drug-related toxicity,” said an internal memo in 2002.
In the same year, the first human clinical trials of the new version began. A Gilead employee laid out a development timeline that would bring the new formulation to market in 2006.
But in 2003, Gilead executives began to sour about pursuing it. They worried that doing so would “ultimately destroy” the growing market for the older version of tenofovir. minutes of an internal meeting, According to a colleague’s email, Gilead’s head of research at the time, Norbert Bischofberger, instructed the company’s analysts to explore the potential of the new formulation as an intellectual property “expansion strategy”.
As a result of that analysis a September 2003 Memorandum It details how Gilead will develop the new formulation to “replace” the original formulation, with the development “timing such that it will be launched in 2015.” In a best-case scenario, company analysts calculate, their strategy will generate more than $1 billion in annual profit between 2018 and 2020.
Gilead made moves to revive the new formulation in 2010, putting it on track for a 2015 release. Gilead chairman and future chief executive John Milligan told investors it would be a “kinder, gentler version” of tenofovir.
After receiving regulatory approval, the company launched a successful marketing campaign aimed at doctors PROMOTED Its new iteration is safer for kidneys and bones than the original.
According to market research firm Ipsos, by 2021, nearly half a million HIV patients in the United States would be taking Gilead products containing the new version of tenofovir.
Susan C. Beachy Contributed to research.
