Drug Trials Snapshots: RIVFLOZA
HOW TO USE THIS SNAPSHOT
The information provided in Snapshots highlights who participated in the key clinical trials that supported the original FDA approval of this drug, and whether there were differences among sex, race, age, and ethnic 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 healthcare provider about the benefits and risks 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 RIVFLOZA Prescribing Information for all 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).
RIVFLOZA (nedosiran)
(Riv-flo-za)
Novo Nordisk, Inc.
Approval date: September 29, 2023
DRUG TRIALS SNAPSHOT SUMMARY:
What is the drug for?
RIVFLOZA reduces urine oxalate in children 9 years of age and older and adults with primary hyperoxaluria type 1 (PH1) and relatively preserved kidney function.
PH1 is a rare disease in which urine oxalate is too high, which over time can harm the kidneys.
How is this drug used?
RIVFLOZA is an injection given under the skin (subcutaneously) once a month.
Who participated in the clinical trials?
FDA approved RIVFLOZA based on evidence from a clinical trial which included 29 patients with PH1. The trial was conducted at 19 sites in 11 countries in North America, Europe, Asia, and Australia.
How were the trials designed?
RIVFLOZA was evaluated in one clinical trial of 29 patients with PH1 who were 9 years of age and older. Patients randomly received either RIVFLOZA or placebo injections once a month for six months. Neither the patients nor the healthcare providers knew which treatment was being given. The benefit of RIVFLOZA was assessed by measuring the amount of oxalate in the urine and comparing it to placebo.
How were the trials designed?
The study used to evaluate RIVFLOZA was a 6-month, parallel group, double-blind, placebo controlled, multicenter trial that randomized 35 patients with primary hyperoxaluria 1 (PH1) or 2 (PH2) in a 2:1 ratio to RIVFLOZA or placebo. Because too few PH2 patients were enrolled to evaluate efficacy in the PH2 population, RIVFLOZA is indicated only for patients with PH1.
DEMOGRAPHICS SNAPSHOT
Figure 1 summarizes how many males and females were enrolled in the clinical trial used to evaluate the efficacy of RIVFLOZA.
Figure 1. Baseline Demographics by Sex
Source: Adapted from FDA Review
Figure 2 summarizes how many patients by race enrolled in the clinical trial used to evaluate the efficacy of RIVFLOZA.
Figure 2. Baseline Demographics by Race
Source: Adapted from FDA Review
Figure 3 summarizes how many patients by age were enrolled in the clinical trial used to evaluate the efficacy of RIVFLOZA.
Figure 3. Baseline Demographics by Age
Source: Adapted from FDA Review
Figure 4 summarizes how many patients by ethnicity enrolled in the clinical trial used to evaluate the efficacy of RIVFLOZA.
Figure 4. Baseline Demographics by Ethnicity
Source: Adapted from FDA Review
Who participated in the trials?
Table 1 provides the number of participants in the trial according to demographic subgroup.
Table 1. Demographic Subgroups in Trial
| Subgroup | RIVFLOZA N=18 n (%) |
Placebo N=11 n (%) |
Total N=29 n (%) |
|---|---|---|---|
| Sex | |||
| Female | 10 (55.6) | 6 (54.5) | 16 (55.2) |
| Male | 8 (44.4) | 5 (45.5) | 13 (44.8) |
| Age, years | |||
| 12 to 17 | 4 (22.2) | 4 (36.4) | 8 (27.6) |
| 9 to11 | 1 (5.6) | 2 (18.2) | 3 (10.3) |
| ≥18 | 13 (72.2) | 5 (45.5) | 18 (62.1) |
| Race | |||
| Asian | 5 (27.8) | 0 (0) | 5 (17.2) |
| Multiple | 0 (0) | 1 (9.1) | 1 (3.4) |
| White | 11 (61.1) | 9 (81.8) | 20 (69) |
| Ethnicity | |||
| Hispanic or Latino | 2 (11.1) | 0 (0) | 2 (6.9) |
| Not Hispanic or Latino | 14 (77.8) | 10 (90.9) | 24 (82.8) |
Source: Adapted from FDA Review
What are the benefits of this drug?
One trial was conducted in participants 9 years of age and older with PH1. In this trial, patients treated with RIVFLOZA had a 50% decrease in urinary oxalate after six months of treatment compared with a 6% increase in patients who received placebo.
What are the benefits of this drug (results of trials used to assess efficacy)?
Percentage reductions from baseline urinary oxalate are provided in Table 2.
Table 2. Mean Percentage Change From Baseline 24-Hour Urinary Oxalate, Days 90 to 180
| Parameter | Placebo | RIVFLOZA |
|---|---|---|
| Mean change from baseline % (95% CI) | 6 (-20, 32) | -50 (-69, -31) |
| Difference (95% CI) | -56 (-80, -33) | |
| p-value | <0.0001 | |
Source: Adapted from FDA Review
Confidence interval nominal only - endpoint selected post hoc without multiplicity adjustment.
Abbreviations: CI, confidence interval
Were there any differences in how well the drug worked in clinical trials among sex, race, and age?
- Sex: The observed effect of RIVFLOZA was similar for females and males.
- Race: The number of patients of races other than White was small; therefore, differences in how RIVFLOZA worked among races could not be determined.
- Age: The observed effect of RIVFLOZA was similar in patients 9 to 11 years of age, 12 to 17 years of age, and adults.
- Ethnicity: The number of Hispanic or Latino patients was small; therefore, differences in how RIVFLOZA worked according to ethnicity could not be determined.
Were there any differences in how well the drug worked in clinical trials among sex, race, and age groups?
Table 3 summarizes the effects of RIVFLOZA according to sex and age.
Table 3. Percentage Change From Baseline Urinary Oxalate by Subgroup
| Subgroup | Treatment Effect* Mean % (95% CI) |
|---|---|
| Sex | |
| Female | -72 (-117, -32) |
| Male | -34 (-60, -7) |
| Age, years | |
| 9 to 11 | -56 (-90, -27) |
| 12 to 17 | -43 (-71, -9) |
| ≥18 | -55 (-83, -29) |
Source: Adapted from FDA Review
* Credible intervals include the relevance of outcomes from other subgroups.
Abbreviations: CI, credible interval
What are the possible side effects?
The most common side effects of RIVFLOZA are injection site reactions, which were reported in seven patients with PH1 (39%) on RIVFLOZA as compared to no patients on placebo.
What are the possible side effects (results of trials used to assess safety)?
Table 4 includes information injection site reactions in patients with PH1.
Table 4. Injection Site Reactions in the RIVFLOZA Group Compared to the Placebo Group in Patients With PH1
| Adverse Reaction | RIVFLOZA N=18 n (%) |
Placebo N=11 n (%) |
|---|---|---|
| Local administration reaction (injection site reaction)a | 7 (39) | 0 |
Source: Adapted from FDA Review
a Includes erythema, pain, bruising, and rash
Abbreviations: PH1, primary hyperoxaluria type 1
Were there any differences in side effects among sex, race and age?
The trials that looked at the side effects of RIVFLOZA were too small to determine if there were differences among sex, race, and age subgroups.
Were there any differences in side effects of the clinical trials among sex, race, and age groups?
Table 5. Overview of Injection Site Reactionsa by Sex, Race, Age, and Ethnicity in Subjects With PH1, Safety Population, Trial DCR-PHXC-201
| Characteristic | All Patients | All Grades | Grades 3 to 4 | |||
|---|---|---|---|---|---|---|
| RIVFLOZA N=18 n (%) |
Placebo N=11 n (%) |
RIVFLOZA N=18 n/Ns (%) |
Placebo N=11 n/Ns (%) |
RIVFLOZA N=18 n/Ns (%) |
Placebo N=11 n/Ns (%) |
|
| Sex | ||||||
| Female | 10 (55.6) | 6 (54.5) | 4/10 (40.0) | 0/6 (0) | 0/10 (0) | 0/6 (0) |
| Male | 8 (44.4) | 5 (45.5) | 3/8 (37.5) | 0/5 (0) | 0/8 (0) | 0/5 (0) |
| Race | ||||||
| Asian | 5 (27.8) | 0 (0) | 1/5 (20.0) | 0/0 (NA) | 0/5 (0) | 0/0 (NA) |
| White | 11 (61.1) | 9 (81.8) | 5/11 (45.5) | 0/9 (0) | 0/11 (0) | 0/9 (0) |
| Multiple | 0 (0) | 1 (9.1) | 0/0 (NA) | 0/1 (0) | 0/0 (NA) | 0/1 (0) |
| Missing | 2 (11.1) | 1 (9.1) | 1/2 (50.0) | 0/1 (0) | 0/2 (0) | 0/1 (0) |
| Age group, years | ||||||
| 9 to 11 | 1 (5.6) | 2 (18.2) | 0/1 (0) | 0/2 (0) | 0/1 (0) | 0/2 (0) |
| 12 to 17 | 4 (22.2) | 4 (36.4) | 2/4 (50.0) | 0/4 (0) | 0/4 (0) | 0/4 (0) |
| ≥18 | 13 (72.2) | 5 (45.5) | 5/13 (38.5) | 0/5 (0) | 0/13 (0) | 0/5 (0) |
| Ethnicity | ||||||
| Hispanic or Latino | 2 (11.1) | 0 (0) | 1/2 (50.0) | 0/0 (NA) | 0/2 (0) | 0/0 (NA) |
| Not Hispanic or Latino | 14 (77.8) | 10 (90.9) | 5/14 (35.7) | 0/10 (0) | 0/14 (0) | 0/10 (0) |
| Missing | 2 (11.1) | 1 (9.1) | 1/2 (50.0) | 0/1 (0) | 0/2 (0) | 0/1 (0) |
Source: Adapted from FDA Review
a Includes erythema, pain, bruising, and rash
Abbreviation: N, number of patients in the safety population; n, number of patients with given characteristic; NA, not applicable; Ns, total number of patients in each category; PH1, primary hyperoxaluria type 1
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.