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  1. Development & Approval Process | Drugs

Drug Trials Snapshots: XURIDEN

HOW TO USE THIS SNAPSHOT
The information provided in Snapshots highlights who participated in the clinical trials that supported the FDA approval of this drug, and whether there were differences among sex, race, and age groups. The “MORE INFO” bar shows more detailed, technical content for each section. The Snapshot is intended as one tool for consumers to use when discussing the risks and benefits of the drugs.

LIMITATIONS OF THIS SNAPSHOT:
Do not rely on Snapshots to make decisions regarding medical care. Always speak to your health provider about the risks and benefits of a drug. Refer to the XURIDEN Prescribing Information for complete information.

XURIDEN (uridine triacetate)
(ZUR-uh-den)
Wellstat Therapeutics Corporation
Approval date: September 4, 2015


DRUG TRIALS SNAPSHOT SUMMARY:

What is the drug for?

XURIDEN is a treatment for a very rare inherited disease called hereditary orotic aciduria. In this disease, the body cannot make uridine, which is necessary for life.

XURIDEN is intended to replace uridine.

Patients with hereditary orotic aciduria have low counts of blood cells, developmental delays, and do not properly gain weight (called failure to thrive).

How is this drug used?

XURIDEN is in the form of orange-flavored granules that are taken once a day usually mixed with soft foods or infant formula or milk.

What are the benefits of this drug?

XURIDEN maintained stability of blood cell counts in all four clinical trial patients.

What are the benefits of this drug?

The table below summarizes hematologic parameters (neutrophil count, white blood cell count, or mean corpuscular volume), individualized by patient. Stability was defined as:

  • Maintenance of abnormal baseline value at Days 28 and 42

Table 2. Primary Efficacy Results

PatientPre-specified hematologic parameter (Age-specific reference range)Primary EndpointBaseline (Day 0)Week 6 (Day 42)Percent Change from Baseline
Patient #1Neutrophil count (1.5 to 8.0 x103/mm3)Stable hematologic value0.950.81-15%
Neutrophil % (26 to 48%)Stable hematologic value212310%
Patient #2White Blood Cell Count (3.8 to 10.6 x109/L)Stable hematologic value7.87.4-5%
Patient #3Mean Corpuscular Volume (75 to 91 fL)Stable hematologic value109.9108.5-1%
Patient #4Mean Corpuscular Volume (72 to 90 fL)Improved hematologic value114.6113.4-2%

Source: Prescribing Information, Section 14, Table 4

During an extension phase of the trial, patients continued to receive XURIDEN. Dosing during the extension phase ranged from 60 mg/kg to 120 mg/kg once daily. After 6 months of treatment, Patient #1’s neutrophil count and neutrophil percent values normalized; hematologic parameters for the other three patients remained stable. Orotic acid and orotidine levels also remained stable for all four patients.

Nineteen (19) case reports of patients with hereditary orotic aciduria have been documented in published literature. Eighteen (18) patients were diagnosed as infants or children between the ages of 2 months and 12 years and were treated with exogenous sources of uridine. One patient, diagnosed at age 28, was not treated with exogenous uridine. All 19 patients presented with significantly elevated levels of urinary orotic acid. Fifteen of 19 had abnormal hematologic parameters at presentation, including 15 with megaloblastic anemia, 8 with leukopenia and at least 2 with neutropenia. Oral administration of exogenous sources of uridine was reported to significantly improve hematologic abnormalities (megaloblastic anemia, leukopenia and neutropenia) within 2 to 3 weeks in almost all documented cases when administered in sufficientamounts. Concentrations of urinary orotic acid were significantly reduced within 1 to 2 weeks of initiating uridine replacement therapy. Some fluctuation in levels of urinary orotic acid were observed, but always at much lower levels than those reported prior to treatment. Improvements in body weight were also documented over time with continued uridine replacement therapy.

The effects of exogenous uridine were maintained over months and years, as long as treatment continued at sufficient doses (with appropriate dose increases based on body weight increases). Most hematologic abnormalities and orotic aciduria reappeared within days up to 2 or 3 weeks when administration of uridine was stopped or the dose was reduced. If treatment was interrupted for longer periods, body weight growth receded. If absolute dosages were not adjusted adequately to compensate for body weight gains, signs and symptoms of hereditary orotic aciduria recurred.

Were there any differences in how well the drug worked in clinical trials among sex, race and age?

The trial that looked at the benefit of XURIDEN was too small (4 patients) to determine if there were any differences in sex, race, and age subgroups.

Were there any differences in how well the drug worked in clinical trials among sex, race, and age groups?

There were insufficient numbers of patients to perform any subpopulation analyses.

What are the possible side effects?

Side effects were not observed in the trial of XURIDEN for up to nine months.

What are the possible side effects (results of trials used to assess safety)?

No adverse reactions were reported with XURIDEN in the clinical trial.

Were there any differences in side effects among sex, race and age?

Side effects were not observed in the clinical trial of XURIDEN for the treatment of hereditary orotic aciduria for up to nine months.

Were there any differences in side effects of the clinical trials among sex, race, and age groups?

No adverse reactions were reported with XURIDEN in the clinical trial.

WHO WAS IN THE STUDIES?

Who participated in the clinical trials?

The FDA approved XURIDEN based on evidence from a clinical trial of 4 patients with hereditary orotic aciduria. The trial was conducted in the USA. The approval was also based on evidence from the medical literature that describes the treatment of 18 patients with hereditary orotic aciduria treated with the active ingredient in XURIDEN.

The table below summarizes enrolled patients by sex, race, and age in the clinical trial.

Table 1. Baseline Demographics

 Patient
1234
SexMaleFemaleMaleMale
RaceWhiteWhiteWhiteWhite
Age (years)61973.5

Source: Adapted from Clinical Review, Table 5

Table 1 provides demographic information for the trial.

How were the trials designed?

Patients received XURIDEN 60 mg/kg once a day for 6 weeks.

The benefit of XURIDEN was measured by looking at stability of blood cell counts.

How were the trials designed?

The efficacy of XURIDEN was evaluated in a 6-week, single-arm, open-label trial of 4 patients with hereditary orotic aciduria as well as a six-month extension phase of the trial. All patients were administered XURIDEN at a dosage of 60 mg/kg once daily during the initial 6 week-phase. Dosing during the 6-month extension phase ranged from 60 mg/kg to 120 mg/kg once daily.

The study assessed changes in the patients’ pre-specified hematologic parameters during the 6-week trial period. The pre-specified hematologic parameters were: neutrophil count and percent neutrophils (Patient 1), white blood cell count (Patient 2), and mean corpuscular volume (Patients 3 and 4).

GLOSSARY

CLINICAL TRIAL: Voluntary research studies conducted in people and designed to answer specific questions about the safety or effectiveness of drugs, vaccines, other therapies, or new ways of using existing treatments.
COMPARATOR: A previously available treatment or placebo used in clinical trials that is compared to the actual drug being tested.
EFFICACY: How well the drug achieves the desired response when it is taken as described in a controlled clinical setting, such as during a clinical trial.
PLACEBO: An inactive substance or “sugar pill” that looks the same as, and is given the same way as, an active drug or treatment being tested. The effects of the active drug or treatment are compared to the effects of the placebo.
SUBGROUP: A subset of the population studied in a clinical trial. Demographic subsets include sex, race, and age groups.

PRESCRIBING INFORMATION

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