The Wonder Drug That Was Lost

Does it work? Yes. Is it safe? Yes. Is it available for thousands of endangered patients? Of course not.

Pharmaceuticals
quimono / Pixabay

Does it work? Yes. Is it safe? Yes. Is it available for thousands of endangered patients? Of course not.

Lipoprotein Lipase Disorder (LPLD) is a genetic mutation that causes the body to be unable to produce an essential protein required to process dietary fat. A victim’s blood becomes white with fat particles that can eventually destroy the pancreas. People with LPLD cannot eat any food that contains fat, nor drink even a drop of alcohol. Women with LPLD cannot have children. Doctors have tried every fat and cholesterol-lowering drug on the market, but none of them work.

A team of Canadian scientists found a cure for LPLD. It took 30 years and a number of acts of serendipity to find it and make it available to the world. It’s called Glybera, and it is the world’s first gene therapy. Yet, according to CBC News, nobody can have it.

Dr. Michael Hayden, who spent decades at the University of British Columbia and the B.C. Children’s Hospital searching for cures to various lipid disorders, took an interest in LPLD in 1986. LPLD affects two to three of every 1 million people worldwide, but in the Saguenay region of Quebec, the ratio is about 200 per million. Hayden assigned the task to John Kastelein, a young doctor from Amsterdam who had just joined Hayden’s lab.

Genetic research was in its infancy at the time, but nonetheless Kastelein attempted to investigate if a genetic mutation was the cause of LPLD. Using a blood sample from a 19-year-old man with LPLD, Kastelein was fortunate to be able to see “a bizarre hole in a gene” that the team would otherwise have been unable to see. It was the first twist of good fortune for Hayden and his team. The team turned to another young doctor who joined the lab, Dr. Colin Ross, who was able to develop a harmless virus specially designed to carry a human gene that could insert itself into the cell and begin replicating the new gene, which would in turn begin producing the required protein that would clear the blood of fat. Ross lab tested the therapy on mice genetically engineered to carry LPLD, and in January of 2002, the test worked. The mice had their white, fat-infused blood turn clear and red.

Before the team could move to human testing, they needed to test the therapy on a larger mammal, and again received a stroke a good luck. Hayden attended a medical conference in Florence, Italy, where he met a New Zealand veterinarian who had found an odd family of cats with white blood. Hayden asked for some blood samples and confirmed that the cats had LPLD. Hayden got some of the cats shipped to his lab and tested the gene therapy on them. It worked. The path to human trials was clear.

Once the drug goes into clinical trials, it leaves the hands of university researchers and enters the hands of doctors and later pharmaceutical companies. Kastelein returned to Amsterdam and formed a drug company, Amsterdam Molecular Therapeutics (AMT), to oversee clinical trials, gain government approval, and produce the cure for LPLD. Human trials began in 2005 in Amsterdam and continued with further trials in Canada three years later. In 2009, AMT had a facility ready to manufacture Glybera, but it took nearly three years for the government in Amsterdam to approve the drug. In 2012, Glybera was formally approved, but AMT also went bankrupt.

The assets, including the licenses for Glybera, were sold to uniQure, a private company. They partnered with an Italian pharmaceutical company to produce the drug, and when it finally hit the European market in 2015 it made headlines, but for all the wrong reasons. Glybera cost $1 million. For a single dose.

Patients couldn’t afford it. Insurance companies would not pay for it. The world’s first gene therapy had exactly one customer, a German woman who was fortunate enough to get her insurance company to pay for the treatment. The single dose of Glybera she received allowed her to go from 40 hospitalizations for pancreatitis to none since taking the drug.

In 2017, the drug was abandoned by its manufacturers. The Italian pharmaceutical company returned the product rights to uniQure, who has no plans to license Glybera in the U.S. or Canada. The costs to produce the drug were simply too high.

Glybera took 30 years and a series of fortunate events to be produced. It has been administered to 31 patients in trials and in its limited life on the free market, and has cured every one of them. However, it will never cure another.

It is a truly lugubrious end to what should otherwise be a triumphant story of human endeavor.