Amid tens of thousands of lawsuits that are pending in state courts all across the US, a new report based on evidence discovered in these court cases reveals Big Pharma giant GlaxoSmithKline (GSK) had, for decades, concealed evidence showing that Zantac could cause cancer.

According to Bloomberg Businessweek, GSK – then known as Glaxo – had been aware of cancer-causing risks with ranitidine, the drug which was marketed as Zantac, even before it was approved by the US Food and Drug Administration (FDA) in 1983. These warnings came from independent researchers but also from Glaxo scientists.

Within five years, Zantac, used to treat or relieve heartburn, acid indigestion and gastric ulcers, became the world’s best-selling medicine and was one of the first to surpass $1 billion in annual sales, according to Reuters. GSK later sold the drug to Pfizer – and Zantac was then sold to Boehringer Ingelheim and finally Sanofi.

In 2019, an online pharmacy detected high levels of a potent carcinogen, NDMA, in Sanofi and its generic equivalents. This led to recalls, followed by a formal FDA withdrawal of the drug in 2020.

This decision was made based on “research showing the amount of NDMA in the products increases the longer the drug is stored and could potentially become unsafe,” Reuters reported, with Fierce Pharma adding that this problem was identified “even under normal storage conditions.”

According to the Bloomberg Businessweek report, the storage issues came in addition to the known risk that “under certain conditions in the stomach, ranitidine could form a potentially dangerous compound” that could cause cancer.

All four aforementioned pharmaceutical companies are now facing tens of thousands of lawsuits in state courts throughout the US “Plaintiffs said the companies knew, or should have known, that ranitidine posed a cancer risk and that they failed to warn consumers,” reports Reuters.

According to Reuters, “While NDMA is found in low levels in food and water, it is known to cause cancer in larger amounts.” Zantac, accordingly, has been linked “to at least 10 types of cancer” in lawsuits that have been filed, including bladder, oesophageal, liver, pancreatic and stomach cancers.

GSK continues to claim that there is “no consistent or reliable evidence” that Zantac caused cancer. So, what is NDMA?

According to Bloomberg Businessweek, “NDMA, which is short for N-Nitrosodimethylamine, is a yellow liquid that dissolves in water. It doesn’t have an odour or much of a taste.” It is most toxic to the liver, and “was first linked to cancer in 1956.”

It adds that “The carcinogen, called NDMA, was once added to rocket fuel and is now used only to induce cancer in lab rats.”

The same report notes that NDMA is “one of a group of chemicals called nitrosamines, which by the 1970s were considered the most potent carcinogens yet discovered. They caused cancer in every species of animal tested. A single dose of less than a milligram of NDMA can mutate mice cells and stimulate tumours, and two grams can kill a person in days.”

According to USA Today, drawing on FDA data, “Nitrosamines are found in water, cured and grilled meats, dairy products and vegetables” and studies have found that they lead to “increased cancer risk if people are exposed to large amounts over long periods of time.”

Stephen Hecht, a professor of cancer prevention at the University of Minnesota, told USA Today that food safety experts have made efforts to reduce nitrosamine levels in foods such as cured meats to far below the levels of the 1970s and 1980s.

Bloomberg Businessweek states that “Every public-health agency, from the Environmental Protection Agency to the FDA to the World Health Organization, says NDMA likely causes cancer in humans.”

The FDA has placed limits on six types of nitrosamines, reports USA Today, equalling “up to one case of cancer per 100,000 people exposed to the contaminant.”

However, the drugs that were recalled and ultimately pulled from the market far exceeded these limits, with estimates of a risk of one cancer case for every 3,000 to 8,000 patients, according to USA Today.

The withdrawal of Zantac and its generic versions resulted in tens of thousands of lawsuits that are still pending – and a process of discovery that has unearthed significant evidence revealing that Glaxo and regulatory bodies were long aware of the presence of NDMA in these medications.

Bloomberg Businessweek reviewed “thousands of pages” of documents, including those arising from the discovery process in the ongoing lawsuits against GSK and other drugmakers, as well as scientific studies, to develop its story, discovering that GSK supported “flawed research” that skewed the narrative away from Zantac’s risks.

As stated in the Bloomberg Businessweek report, “Proving that a particular person’s cancerous cells were mutated by a company’s drug is complicated. Glaxo’s decisions suggest it never wanted to consider that possibility. The clues were there. The documents show that Glaxo preferred not to find them.”

The report continued, “From ranitidine’s beginning to its end, Glaxo had been warned by its own scientists and independent researchers about the potential danger. An account of those four decades emerges in hundreds of documents, thousands of pages, many of which have never been made public.

“Bloomberg Businessweek reviewed court filings, many still under seal, as well as studies, FDA transcripts and new drug applications obtained via Freedom of Information Act requests. They show that the FDA considered the cancer risks when approving ranitidine. But Glaxo didn’t share a critical study.

“Over the years, the company also backed flawed research designed to minimize concerns and chose not to routinely transport and store the medication in ways that could have eased the problem. Glaxo sold a drug that might harm people, tried to discount evidence of that and never gave anyone the slightest warning.”

The report presents evidence indicating that Glaxo – and later GSK – were aware that NDMA could be present in Zantac, both as a result of how it was metabolised in the human stomach and also by naturally occurring even under ordinary storage conditions.

According to the report, ranitidine was first developed by Glaxo scientists in the 1970s, and a US patent for it was granted in 1978. As stated by the report, the process of developing ranitidine and getting it approved was swift.

“They developed ranitidine quickly, and the US Food and Drug Administration reviewed it quickly. Glaxo gave it the brand name Zantac,” said Bloomberg Businessweek. It was soon marketed as being “better and safer” than the leading heartburn drug at the time, Tagamet.

However, the warning signs were already there. According to Bloomberg Businessweek, a US government cancer researcher and biochemist, William Lijinsky, had found in 1969 that nitrosamines could form in the stomach, exacerbated by the presence of nitrites, “a common chemical found in cured and grilled meat and in beer and coffee and vegetables” found to be “common causes of heartburn and acid reflux.”

Lijinsky’s solution to this, presented in published studies and in Congressional testimony in the 1970s, was to limit sodium nitrite levels in food. Already, by the late 1970s, Lijinsky identified roadblocks that were not allowing his warnings to be fully heeded.

“It seems to me that the regulatory agencies have been less than eager to act in the matter of nitrites and nitrosamines,” he testified before Congress in 1977. “There has been ample information available, if they had sought it. There is, of course, immense opposition by the manufacturing companies to any change.”

According to Lijinsky’s wife, Rosalie Lijinsky, herself a genetic toxicologist who recently retired from the FDA, William lost federal funding for his research due to pressure from both the food and pharmaceutical industries.

• The Defender report / By Michael Nevradakis, based in Athens, Greece, is a senior reporter for The Defender