Cerezyme and VPRIV for Patients with Type 1 Gaucher Disease


Prior to the introduction of enzyme replacement therapy, symptom relief was a major focus of Gaucher disease management.

Gaucher disease is a chronic, progressive, autosomal-recessive inherited metabolic disorder that affects fewer than 10,000 people worldwide. Patients with Gaucher disease have a deficiency of glucocerebrosidase, an enzyme stored in the lysomes of macrophages that is vital to breaking down glucocerebroside. With insufficient enzyme activity, these lipids begin to accumulate in the spleen, liver, lungs, kidneys, brain, and bone marrow. Type 1 Gaucher disease can present a wide array of symptoms, including easy bleeding and bruising, anemia, excessive fatigue, and bone and joint pain.

Prior to the introduction of enzyme replacement therapy (ERT), symptom relief was a major focus of Gaucher disease management. Treatments included various pain reduction therapies, blood transfusions, orthopedic surgery for bone and joint involvement, and possibly splenectomy.1 While these options still have a place in the management of Gaucher disease, the treatment paradigm shifted with the advent of targeted ERT. Genzyme Corporation (Cambridge, MA) partnered with the National Institutes of Health (Baltimore, MD) in 1991 to develop such ERT, and in 1994 the company introduced Cerezyme (imiglucerase for injection) for the treatment of type 1 Gaucher disease. Since then, clinicians have been able to target the disease process itself, thereby alleviating and even reversing many of the effects of type 1 Gaucher disease.

For years, Cerezyme has been the standard treatment for type 1 Gaucher disease. The approval in March 2010 of VPRIV (velaglucerase alfa for injection), a hydrolytic lysosomal glucocerebroside-specific enzyme from Shire Human Genetic Therapies, Inc. (Dublin, Ireland), gives patients with type 1 Gaucher disease another option to treat the hereditary condition. The availability of VPRIV, combined with supply issues that have plagued Genzyme over the last 12 months, have prompted many patients to ask their physicians to switch their prescription from Cerezyme to VPRIV. Some prominent physician researchers have offered their views on prescribing either medication.

“I can comfortably say that newer is different, not better,” says Barry E. Rosenbloom, MD, a founding member of Tower Hematology Oncology Medical Group (Beverly Hills, CA). “There’s nothing better about velaglucerase [as compared with Cerezyme] that I can judge. It’s a similar product.”

Cerezyme Supply Problems and Backlash

On June 16, 2009, Genzyme temporarily suspended all production of Cerezyme at its Allston, Massachusetts facility after identifying a viral contamination in a bioreactor used to make the drug. Although the facility has since been sanitized and is fully functional, the temporary suspension of production constrained the supply of Cerezyme.

Shire, looking to plug the therapeutic gap in the market, filed for and received FDA approval for fast-track designation of VPRIV. The company also began offering the drug for free to patients with type 1 Gaucher disease who were affected by the Cerezyme shortage.

“We’ve put 23 patients on [VPRIV],” says Gregory A. Grabowski, MD, director of the Division of Human Genetics at Cincinnati Children’s Hospital Center (Cincinnati, OH) and principal investigator in the recent TKT-034 study that demonstrated the safety of switching patients from Cerezyme to VPRIV. “There is some backlash toward Genzyme; it has been a difficult problem for everyone, including the company.”

“Some patients have felt betrayed by Genzyme,” explains Dr. Rosenbloom. “I think they felt let down; mainly, they were scared. A number of patients made the choice [to switch] on their own, for reasons that have nothing to do with cost, effectiveness, or side effects. [They switched] simply because [VPRIV] has been available. It was good public relations for [Shire], and to some degree they got more data from it.”

Gregory M. Pastores, MD, an associate professor for the departments of neurology and pediatrics at the NYU School of Medicine (New York City) and a principal investigator in phase III trials for both Cerezyme and VPRIV, reported that about 50 of his 300 patients with type 1 Gaucher disease have switched to VPRIV therapy largely because of the supply issues with Cerezyme.

“Patients were not feeling well during the period where there was either an interruption in their treatment or a reduction in their dose,” recalls Dr. Pastores. “I think that level of anxiety drove [patients] to ask for another enzyme therapy, and now that they’ve had experience with VPRIV, their anxiety has been allayed and they’ve decided to stay with it.” He adds, “The fact that there was an alternative [seemed to] rescue the whole situation, which could have been potentially catastrophic.”

A Side-by-Side Comparison

Dr. Rosenbloom explains that Cerezyme and VPRIV have never been compared head to head, and he doubted they ever will. The main reason is that one company would have to purchase their competitor’s drug and give it to patients for free because, “how can you compare it and have patients pay for it? That’s hard to do with expensive drugs,” he says.

These thoughts are echoed by Dr. Grabowski, who explains that the ideal study would involve treatment-naive patients with type 1 Gaucher disease randomized to receive Cerezyme or VPRIV. The problem, however, is a lack of patients with type 1 Gaucher disease who have never received therapy.

Examining the available data, Dr. Grabowski notes that there is nothing he can identify—either statistically or from speaking with patients— that would indicate a major difference between the two agents. “It appears as though both [drugs] have the same adverse event profile; around 7% to 8% of patients have some kind of adverse event with either drug, and they’re mild in general,” says Dr. Grabowski. He adds, “There aren’t enough patients on VPRIV yet to talk about whether there are the same number of serious adverse events.”

According to the TKT-034 study, “a range of adult and pediatric patients with Gaucher disease type 1 were safely transitioned from imiglucerase (15-60 U/kg every other week) to the same number of units of velaglucerase alfa.” With both agents administered intravenously on an every-other-week basis, study results showed that for patients transitioned to VPRIV, “clinical measures of disease remained stable over 12 months.”

One difference between the drugs, notes Dr. Pastores is that 1 in 100 patients taking VPRIV have developed antibodies to the agent; with Cerezyme, he says, the ratio has historically been approximately 15 in 100. “If in fact those signals prove to be true over time, then I think it’s telling us that there’s something the body senses. Whether that will translate into an advantage for VPRIV or not remains to be seen.”

Dr. Grabowski, however, says it is difficult to make the antibody comparison for several reasons. “Are the tests for antibodies identical assays? Are they really comparative from one company to another, or is there something inherently different about the assays?” Either way, he says that the adverse event profile of the two drugs is more important. “There have been very, very few [adverse events] with Cerezyme, but there aren’t enough numbers to talk about that yet with VPRIV.”

Moving forward, Dr. Rosenbloom believes that Genzyme “is a smart company” that is currently developing other products to treat type 1 Gaucher disease, including an oral agent—eliglustat tartrate (formerly Genz-112638)—currently in phase III trials. “I can tell you, patients are clamoring for that,” he says.

Dr. Grabowski agrees. “There are a lot of people interested in Genzyme’s new oral agent.” From a convenience factor alone, he said, [an oral agent] would be a huge step forward. “The phase II data look really promising. If it continues to be so in phase III, and the safety profile seems to be the same, [eliglustat tartrate will be] a really important drug.”

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