More Rapid Infusions of VPRIV Still Safe, Effective for Gaucher Type 1 Patients, Study Finds

More Rapid Infusions of VPRIV Still Safe, Effective for Gaucher Type 1 Patients, Study Finds

Shortening the duration of VPRIV (velaglucerase alfa) infusions from 60 to 10 minutes does not affect the safety or effectiveness of the enzyme replacement therapy in patients with Gaucher disease type 1, a study reports.

The study, “Rapid intravenous infusion of velaglucerase‐alfa in adults with type 1 Gaucher disease,” appeared in the American Journal of Hematology.

Gaucher disease type 1 is caused by mutations in the GBA gene, which leads to insufficient levels of glucocerebrosidase (GBA), an enzyme that breaks down a fat molecule called glucocerebroside.

For Gaucher patients, enzyme replacement therapies deliver a modified version of GBA, which then breaks down the excess fat molecules and keep symptoms of the disease in check.

Besides Shire‘s VPRIV, other enzyme replacement therapies for Gaucher include Cerezyme (imiglucerase), by Sanofi Genzyme, and Elelyso (taliglucerase alfa), by Pfizer.

Because hourlong infusions of enzyme replacement therapies every other week can impact patients’ quality of life, namely having to take time off school or work, there have been various reports of some patients drastically reducing the duration of their infusions to as little as two to five minutes. Interestingly, no negative effects from these shortened times have been reported.

Rapid intravenous infusion of medications can induce various undesired reactions, including mild irritations at the injection site, inflammatory responses, and life-threatening hypersensitivities. Even patients who do not develop a reaction at a standard, or lower, rate of infusion may be affected.

To look into the possible effects of a shortened infusion time of enzyme replacement therapies, researchers assessed the safety of reducing the infusion duration of VPRIV from 60 to 10 minutes, using a step-wise reduction in time and enabling home infusions in the final phase. According to the scientists, they chose to test VPRIV due to its good safety and tolerability profiles in clinical trials and practice.

Supported by a grant from Shire, the study was conducted at the Shaare Zedek Medical Center in Israel. Eligible patients were adults with at least three months of exposure to VPRIV at a stable dose and no treatment-related adverse events.

Each infusion consisted of 100 ml of VPRIV. For safety reasons, the patients’ blood pressure, heart rate, and temperature were controlled before, at the start, and at the end of infusions.

To assess effectiveness, they measured the concentration of hemoglobin — the protein carrying oxygen throughout the body — platelet counts, and spleen and liver volume — normally enlarged in Gaucher patients — as well as levels of the Gaucher biomarker glucosylsphingosine (lyso-Gb1). Participants also completed a questionnaire to evaluate disease impact.

The study included a total of 15 patients, with a mean age of 32, who had been receiving treatment with VPRIV for a mean of 9.6 years. Pre-study dosages — between 15 and 60 units/kg body weight — were maintained.

The 10-minute infusions did not cause any severe adverse events either at the clinic or at home. Only one patient reported a mild adverse event, experiencing a feeling of coldness in the infused arm during the procedure. This patient was withdrawn from the trial after becoming pregnant. A second patient withdrew for personal reasons.

All patients showed stable blood parameters, spleen and liver volumes, and lyso-Gb1 levels. Questionnaire scores also remained stable between the start and end of the study in the 13 patients who completed the trial. No patients developed antibodies against the treatment.

Data also showed that VPRIV’s concentration in the blood reached higher levels with rapid infusions, but remained in the blood for longer periods with 60-minute infusions.

“We established that step-wise shortening of infusion duration, from one hour to 10 minutes in three stages over 6 months and as home infusions, did not compromise the safety or efficacy of treatment in adult patients with type 1 GD receiving velaglucerase alfa (VPRIV),” the researchers wrote.

Twelve patients continued into a 15-month extension phase. Investigators said the willingness of patients to continue with the rapid infusions confirms the procedure’s convenience and is in line with anecdotal evidence.

“Moreover, this approach may also have broader implications for healthcare providers and payers because of the possibility of reducing the considerable costs engendered by both prolonged intravenous administrations and the reliance on a hospital setting,” they said.

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