How Gilead Leveraged Slow Walking for a Promising HIV Treatment

In 2004, Gilead Sciences decided to stop pursuing a new HIV drug. the General explanation is that it was not sufficiently different from the current treatment to warrant further development.

There was something else at play in the secret though. Gilead was Make plan to delay the launch of the new drug to boost profits, even though executives had reason to believe it might be safer for patients, according to a set of internal documents released in the litigation against the company.

Gilead, one of the world’s largest drugmakers, appears to be adopting an industry-hacking tactic: manipulating the US patent system to protect lucrative monopolies over its best-selling drugs.

At the time, Gilead already had a couple of blockbuster HIV treatments, both powered by a version of a drug called tenofovir. The first of these treatments was due to lose patent protection in 2017, at which point competitors will be free to offer cheaper alternatives.

The most promising drug, which was in the early stages of testing, was an updated version of tenofovir. Gilead executives knew it contained May be less toxic on more patients’ kidneys and bones than in the previous iteration, according to internal memos discovered by lawyers suing Gilead on behalf of the patients.

Despite these potential benefits, executives concluded that the new version risked competing with the company’s existing, patented formulation. If they delay releasing the new product until shortly before existing patents expire, the company can dramatically increase the period of time that at least one HIV treatment remains patented.

The “patent extension strategy,” as Gilead’s documents have repeatedly called it, would allow the company to keep high prices for tenofovir-based drugs. Gilead could switch patients to its new drug before the cheaper ones hit the market. By setting tenofovir on a path to remain a money-making juggernaut for decades, the strategy was likely worth billions of dollars.

Gilead ended up introducing a version of the new treatment in 2015, nearly a decade after it would have become available had the company not paused development in 2004. Its patents now extend Until 2031 at least.

The delayed release of the new treatment is now the subject of state and federal lawsuits, as some 26,000 patients who took Gilead’s old HIV drugs allege the company unnecessarily exposed them to kidney and bone problems.

In court filings, attorneys for Gilead said the allegations were unfounded. They denied that the company had halted development of the property to increase profits. They 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.

“Had Gilead been motivated by profit alone,” the attorneys wrote, “the plaintiffs say, the logical decision would have been to accelerate development of the remake.”

“The research and development decisions made by the company have always been, and continue to be, guided by our focus on delivering safe and effective medicines to the people who prescribe and use them,” Gilead’s chief attorney, Deborah Tillman, said in a statement.

Today, an expensive Gilead drug containing the new iteration of tenofovir accounts for half of the HIV treatment and prevention market, according to IQVIA, an industry data provider. One widely used product, Descovy, is priced at $26,000 annually. Generic versions of its predecessor, Truvada, whose patents have expired, now cost less than $400 a year.

If Gilead had gone ahead with its development of an updated iteration of the drug back in 2004, its patents would either have expired by now or they would sooner.

“We should all take a step back and ask: How did we allow this to happen?” said James Krelenstein, a longtime AIDS activist who has advised attorneys to sue Gilead. “This is what happens when a company deliberately delays the development of an HIV drug for monopolistic purposes,” he added.

Gilead’s obvious maneuver with tenofovir is so common in the pharmaceutical industry that it has a name: product hopping. The companies get rid of their monopoly on the drug and then, shortly before generic competition arrives, switch — or “jump” — patients to a newer, patented version of the drug 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 is likely to extend the company’s revenue streams for years after the new version of the drug faces its first competition from other companies in 2028. (Julie Cunningham, a Merck spokeswoman, denied being involved in product hopping and said the new convenience version is “a new level aimed at bringing a higher level to patients.”

Christopher Morten, an expert on pharmaceutical patent law at Columbia University, said the Gilead case illustrates how the US patent system creates incentives for companies to slow innovation.

“Something went very wrong here,” said Mr Morten, who provides pro bono legal services to an HIV advocacy group in 2019. no avail It defied Gilead’s efforts to extend the life of its patents. “The patent system has encouraged Gilead to delay 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, battling kidney disease and osteoporosis. He said that four years ago, when he was 62, 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 turned off Truvada, which he thought was hurting him. By then, he said, he had become too ill to work and retired from his job as the airline’s director of operations.

He said, “I feel like all this time was taken away from me.”

First synthesized in the 1980s by researchers in what was then Czechoslovakia, 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 a product containing Gilead’s first iteration of tenofovir. Four more will follow. The drugs prevent the reproduction of HIV, the virus that causes AIDS.

These have been game-changers in the war against AIDS, and are credited with saving millions of lives worldwide. The drugs were used not only as a treatment but also as a preventative for those at risk of infection.

But a small percentage of patients who were taking the drug to treat HIV developed kidney and bone problems. It has proven particularly risky when combined with sedative drugs to enhance its efficacy – a practice that was once popular but has since fallen out of favor. the Global Health Organization And the United States National Institutes of Health Use of the original version of tenofovir is discouraged in people with osteoporosis or kidney disease.

The newer version does not cause these problems, but it can cause weight gain and higher cholesterol levels. For most people, experts say, tenofovir-based drugs — the first of the two known as… TDFcalled the second tuff Offer roughly equal risks and rewards.

Internal company records from the early 2000s show that Gilead executives sometimes wrestled over whether to rush the new formulation to market. At some points, the documentation described the two iterations of tenofovir as being similar from a safety point of view.

But other notes indicate that the company believed the updated formula was less toxic, based on lab and animal studies. Those studies showed that the newer formulation had two advantages that could reduce side effects. It was much better than the original at getting tenofovir into target cells, which means much less of it escapes into the bloodstream, where it can travel to the kidneys and bones. It may be given at a lower dose.

The new version “may translate to a better side effect profile and less drug-related toxicity,” an internal note read in 2002.

That same year, the first human clinical trial of the newer version began. A Gilead employee charted a development timeline that would have brought the newer formula to market in 2006.

But in 2003, Gilead executives began to feel weary of pushing it forward. They were concerned that doing so would “ultimately cannibalize” the growing market for the older version of tenofovir, according to minutes from an internal meeting. Norbert Bischofberger, Gilead’s head of research at the time, instructed the company’s analysts to explore the possibilities of the new formulation as an “extension strategy” for IP, according to a colleague’s email.

As a result of this analysis a September 2003 note that described how Gilead would develop the newer formula to “replace” the original, with development “timed to launch in 2015.” In a best-case scenario, the company’s analysts calculate, their strategy will generate more than $1 billion in annual profits between 2018 and 2020.

Gilead moved to revive the newer formulation in 2010, which put it on track for a 2015 release. John Milligan, Gilead’s president and future CEO, told investors it would be a “gentle, gentler version” of tenofovir.

After obtaining regulatory approvals, the company embarked on a successful marketing campaign targeting physicians promotion Its new iteration is safer for the kidneys and bones than the original.

By 2021, according to market research firm Ipsos, nearly half a million HIV patients in the United States were taking Gilead products containing the new version of tenofovir.

Susan C Beachy Contribute to the research.