Drug Trials Snapshots: NULIBRY
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.
Some of the information in this Snapshot is for presentation purposes and does not represent the approved conditions of use of this drug. Refer to the NULIBRY Prescribing Information for all of the approved conditions of use of this drug (e.g., indication(s), population(s), dosing regimen(s), safety information).
Snapshots are limited to the information available at the time of the original approval of the drug and do not provide information on who participated in clinical trials that supported later approvals for additional uses of the drug (if applicable).
NULIBRY (fosdenopterin)
(noo lye bree)
Alcami Carolinas Corporation
Approval date: February 26, 2021
DRUG TRIALS SNAPSHOT SUMMARY:
What is the drug for?
NULIBRY is a prescription medicine used to reduce the risk of death in patients with molybdenum cofactor deficiency (MoCD) Type A.
How is this drug used?
NULIBRY is given once a day into the vein (intravenously), through a special access catheter or port placed by a healthcare provider. The dose of NULIBRY varies depending upon the age and weight of the patient.
What are the benefits of this drug?
NULIBRY was shown to improve survival in children with molybdenum cofactor deficiency (MoCD) Type A.
What are the benefits of this drug (results of trials used to assess efficacy)?
The survival analysis was based on mortality data from 13 treated patients across 3 trials and 18 untreated patients in a separate natural history study who were matched to the treated patients based on the type of disease mutation. The survival benefit was also seen when comparing the 13 treated patients with all 37 untreated patients (matched and unmatched) in the natural history study.
Table 1: Overall Survival in Patients with MoCD Type A Treated with NULIBRY or rcPMP Versus Genotype-Matched Untreated Patients in Historical Control
Summary |
Treated |
Matched Untreated |
|
Number of Deaths (%) |
2 (15%) |
12 (67%) |
|
Hazard Ratio for Risk of Death (95% CI) 1 |
0.18 (0.04, 0.72) |
|
|
Mean Survival Time (Months) |
||
|
At 1 year (95% CI) 2 |
11 (9, 13) months |
10 (8, 12) months |
|
At 3 years (95% CI) 3 |
32 (26, 37) months |
24 (17, 31) months |
|
Survival Probability |
||
|
1 year (95% CI) |
92% (57%, 99%) |
67% (40%, 83%) |
|
3 years (95% CI) |
84% (49%, 96%) |
55% (30%, 74%) |
Source: NULIBRY Prescribing Information
1 Based on Cox proportional hazards model regressing survival status on an indicator variable denoting treatment status. The 95% CI is based on the modified score test statistic under the Cox model. The hazard ratio represents the risk of death in the treated patients compared to the untreated historical control patients.
2 Based on the area under the survival curves up to 1 year of follow-up.
3 Based on the area under the survival curves up to 3 years of follow-up.
Were there any differences in how well the drug worked in clinical trials among sex, race and age?
The trials that evaluated the benefit of NULIBRY were too small to determine if there were any differences in sex, race, and age subgroups.
What are the possible side effects?
Common side effects include catheter-related complications, fever, viral infections, pneumonia, ear infections, vomiting, coughing and sneezing, common cold/flu infections, stomach flu-like infections, diarrhea, and bacteria in the blood.
Based on findings in animal studies, NULIBRY also has the potential to cause ultraviolet (UV) light-induced skin damage. Patients treated with NULIBRY should avoid exposure to direct sunlight and artificial UV light and adopt precautionary measures (e.g., wear protective clothing and hats, use broad-spectrum sunscreen with high sun protection factor [SPF] and wear sunglasses) when exposed to the sun.
What are the possible side effects (results of trials used to assess safety)?
Assessment of adverse reactions for NULIBRY is based on data from three trials in treated patients with a confirmed diagnosis of MoCD Type A. In trials 1 and 2, patients received a daily intravenous infusion of NULIBRY. The median exposure to NULIBRY was 4.3 years and ranged from 8 days to 5.6 years. The table below presents the most common adverse reactions reported in two or more NULIBRY-treated patients.
Table 2 Common Adverse Reactions Reported in Two or More NULIBRY-Treated Patients with MoCD Type A (Studies 1 and 2)
|
Adverse Reactions |
NULIBRY-Treated Patients (N=9) n (%) |
|
Catheter-related complications1 |
8 (89%) |
|
Pyrexia |
7 (78%) |
|
Viral infection |
5 (56%) |
|
Pneumonia |
4 (44%) |
|
Otitis Media |
4 (44%) |
|
Vomiting |
4 (44%) |
|
Cough/Sneezing |
4 (44%) |
|
Upper viral respiratory infection |
3 (33%) |
|
Gastroenteritis |
3 (33%) |
|
Diarrhea |
3 (33%) |
|
Bacteremia |
3 (33%) |
|
Abdominal pain |
2 (22%) |
|
Influenza |
2 (22%) |
|
Lower respiratory tract infection |
2 (22%) |
|
Viral tonsillitis |
2 (22%) |
|
Oropharyngeal pain |
2 (22%) |
|
Rash maculo-papular |
2 (22%) |
|
Anemia |
2 (22%) |
|
Eye swelling |
2 (22%) |
|
Seizure |
2 (22%) |
|
Agitation |
2 (22%) |
Source: NULIBRY Prescribing Information
Abbreviations: MoCD = molybdenum cofactor deficiency
1 Catheter-related complications included complication associated with device, catheter site abscess, catheter site discharge, catheter site extravasation, catheter site pain, catheter site infection, catheter site inflammation, device dislocation, device leakage, device occlusion, and vascular device infection.
In trial 3, adverse reactions for treated patients were similar to those trial 1 and 2 except for the following additional adverse reactions that were reported in more than one patient: sepsis, oral candidiasis, varicella, fungal skin infection and eczema.
Were there any differences in side effects among sex, race and age?
The trials that looked at the side effects of NULIBRY were too small to determine if there were any differences in sex, race, and age subgroups.
WHO WAS IN THE CLINICAL TRIALS?
Who participated in the clinical trials?
The FDA approved NULIBRY based on evidence from 31 patients with molybdenum cofactor deficiency (MoCD) Type A from 3 trials which contributed a total of 13 patients who received NULIBRY and 1 study which contributed natural history data from 18 untreated patients . These were conducted at sites in 15 countries including Australia, Canada, Germany, Israel, Italy, Japan, Malaysia, Netherlands, Poland, Saudi Arabia, Spain, Tunisia, Turkey, United Kingdom and United States.
Figure 1 summarizes how many males and females were enrolled in the combined clinical trials and study used to evaluate the efficacy of NULIBRY.
Figure 1. Baseline Demographics by Sex
Source: FDA Review
Figure 2 summarizes the percentage of patients by race enrolled in the combined clinical trials and study used to evaluate the efficacy of NULIBRY.
Figure 2. Baseline Demographics by Race
Source: FDA Review
Figure 3. Baseline Demographics by Age
The mean age at time of initiation of NULIBRY in patients was 14 days of age with a range of 1 day to 69 days of age.
How were the trials designed?
NULIBRY was evaluated using data from 3 treatment trials compared to data from a natural history study of untreated patients with molybdenum cofactor deficiency (MoCD) Type A. The benefit of NULIBRY was assessed by comparing the time to death in treated pediatric patients (n=13) to untreated pediatric patients (n=18).
Safety was evaluated in 13 pediatric patients with MoCD Type A who were in the 3 treatment trials. The median duration of exposure to NULIBRY during the trials was 4.3 years.
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.
NULIBRY Prescribing Information
