In 1991, the U.S. Food and Drug Administration (FDA) approved the first treatment ever for Gaucher disease (pronounced go-SHAY). This treatment, called enzyme replacement therapy (ERT), replaces the enzyme missing in patients with Gaucher disease with a modified version of the enzyme. ERT helps the body break down glucocerebroside, a fatty chemical that accumulates in patients’ organs and blood due to an enzyme deficiency.
ERT was the first effective treatment for Gaucher disease, forever changing thousands of lives. This post will look at the history and significance of ERT approval, including how it paved the way for new treatments for Gaucher disease and other disorders.
Discovering How to Treat Gaucher Disease
In 1964, Dr. Roscoe Brady at the National Institutes of Health (NIH) discovered that a specific enzyme deficiency causes symptoms first identified by Philippe Gaucher in the 1880s.
In 1966, Dr. Brady first suggested the possibility of extracting the missing enzyme and injecting it in patients with Gaucher disease. Using human placentas, his team was able to isolate this missing enzyme, called glucocerebrosidase (GBA). He and his team discovered that they could extract the enzyme from human placentas, injecting it into a few patients in 1973 with positive results.
However, the injected enzyme did not last long, so Dr. Brady focused his research on changing the enzyme to specifically target the cells that break down glucocerebroside. He and his team were successful, but the lab couldn’t make enough of the modified enzyme to establish clinical trials.
Dr. Brady then formed a relationship with scientist and entrepreneur Henry Blair and his business partner Henri Termeer. In 1981, Blair and Termeer founded Genzyme to begin producing the enzyme in quantities needed for clinical trials.
The First Clinical Trials
In 1983, Dr. Brady and his colleagues were finally ready to conduct the first clinical trial using the modified enzyme. Brian Berman, now president and CEO of the National Gaucher Foundation (NGF), was the first patient to successfully receive ERT.
When Brian’s mother, Dr. Robin Ely, previously learned that her very ill 3-year-old had Gaucher disease, she closed her medical practice to volunteer at the NIH. After Dr. Brady and Dr. John Barranger examined Brian, they decided to include him in the first clinical trial.
He received 7 consecutive weekly doses and experienced a miraculous recovery. Then the lab ran out of enzyme, and all of his symptoms returned. This result happened several times.
“I was 4 years old at the time, but I still have memories of the experience,” says Brian. “They would make a little for me, I’d get better, then they’d run out and I’d get sick again. It was a real roller-coaster ride.”
Only later did he realize that it took 40 human placentas to get enough enzyme for one dose for him as a child. Over the next few years, Genzyme began slowly increasing its capacity to manufacture enzyme for additional clinical trials.
Expanding Funding and Clinical Trials
In 1984, the Berman family founded the NGF to help scientists raise funds to continue clinical trials. Researchers required more than 22,000 placentas for just a 1-year dose for a single patient, and investors were skeptical because the disease was so rare.
The turning point came in 1987 when Dr. Ely went with Genzyme CEO Henri Termeer to speak at several investors meetings. She was 8 months pregnant, and her words helped convince investors to provide $10 million to expand production facilities. That was just 17 days before the economic slump of 1987.
Expanded clinical trials over the next 4 years proved that ERT was a remarkably safe and effective treatment, improving symptoms for all patients studied.
In 1991, the FDA approved Genzyme’s ERT drug Ceredase (alglucerase) for patients with Gaucher disease type 1. Patients nationwide with Gaucher disease started receiving Ceredase in 1992, reversing symptoms and halting disease progression for patients who had suffered for years.
ERT: Before and After
It is impossible to overstate how dramatically ERT changed the lives of patients with Gaucher disease. Before ERT, treatment often involved spleen removal, which relieved some symptoms but did not stop progressive worsening of the disease. Doctors sometimes used bone marrow transplants, but these are risky procedures.
Limited treatment options meant patients often experienced debilitating complications, which could even be fatal. Parents had to watch their children suffer through painful and sickly childhoods, with many patients confined to wheelchairs in adulthood.
“I was sick and bled a lot,” says Brian, adding that he also had to deal with bruising issues, bone pain and exhaustion. He recalls a childhood marked more by medical procedures than free-spirited playing. “It’s such a stark contrast to my experience with my own kids. I’m so grateful,” he says.
Recent Developments in Gaucher Disease Treatment
Ceredase, the first ERT drug, paved the way for other developments in Gaucher disease treatment. Scientists have developed new ERT drugs, as well as substrate reduction therapy (oral medication) for Gaucher disease to decrease the body’s production of glucocerebroside.
Key milestones in Gaucher disease treatment include:
- 1994: The FDA approves Cerezyme® (imiglucerase), an ERT drug Genzyme developed as a successor to Ceredase.
- 2002: The FDA approves Zavesca® (miglustat), an oral SRT drug developed by Actelion Pharmaceuticals.
- 2010: The FDA approves VPRIV® (velaglucerase alfa), an ERT drug developed by Shire.
- 2012: The FDA approves ELELYSO® (taliglucerase alfa), an ERT drug developed by Pfizer.
- 2014: The FDA approves Cerdelga® (eliglustat), an oral SRT drug developed by Genzyme.