Primary hyperoxaluria type 1 (PH1) is a rare genetic disease that causes high levels of a substance called oxalate to build up in your blood or urine (pee). Oxalate can combine with calcium in your body and form a type of kidney stone, called a calcium oxalate stone, that can form in your kidney and bladder. Calcium oxalate stones can form in the blood vessels of the kidneys, which makes it harder for the kidneys to work properly. As kidney function worsens, oxalate builds up in the blood and causes even more stones to form. Without treatment, PH1 can eventually cause kidney failure and may cause problems in other areas of your body, such as your eyes, heart, skin, and bones.
Rivfloza (nedosiran) is a medicine approved to lower oxalate levels in the urine in people with PH1 aged 2 years or older whose kidneys are still working fairly well.
How Does Rivfloza Work for PH1?
Rivfloza is a medicine designed to work mainly in the liver, where oxalate is made. After being injected under the skin, Rivfloza uses special sugar molecules attached to it to guide it directly to liver cells. Once inside these liver cells, Rivfloza uses a process called RNA interference to block the instructions that the cells use to make a protein called lactate dehydrogenase. Lactate dehydrogenase helps make oxalate, so by lowering the amount of this protein in the liver, the body produces less oxalate. This makes it less able to build up and cause problems in the kidneys and other areas of the body.
How Is Rivfloza Given?
Rivfloza is given as an injection under the skin (subcutaneous) once a month. The dose that you get will depend on how much you weigh. Each injection can be given by a health care provider. After proper training, you or a caregiver may also give the injection. Anyone younger than 12 years should have their injection given by a caregiver or health care provider.
Your prescription for Rivfloza will either come as a prefilled syringe or a vial containing a single dose. The vial should only be used by a health care provider or an adult who has received proper training from a health care provider. Before you use it, the medicine should be stored in the refrigerator between 36 F and 46 F (2 C and 8 C) and kept in the carton to protect it from direct heat and light. If needed, Rivfloza can be stored at room temperature between 59 F and 86 F (15 C and 30 C) for up to 28 days (four weeks). If Rivfloza is removed from the refrigerator, mark down the date that it was removed on the carton and throw it away if it is not used within 28 days.
Take Rivfloza out of the refrigerator 30 minutes before you are ready to inject it to let it come up to room temperature. Follow the medicine’s Instructions for Use for detailed directions on how to prepare the dose. When you are ready, inject Rivfloza under the skin in your stomach area (abdomen) or upper thigh. Avoid injecting Rivfloza within 2 inches of your belly button; do not inject into a vein or into any areas that are bruised or scarred. If you are using the vial and the dose requires more than one injection, make sure to inject each syringe into a different place.
After you have used your dose of Rivfloza, make sure to throw away any used needles and syringes in an FDA-approved sharps container. You can find out more about sharps disposal in the state you live in on the FDA website at fda.gov/safesharpsdisposal.
How Was Rivfloza Studied for PH1?
The safety and effectiveness of Rivfloza in people with PH1 (whose kidneys were still working fairly well) were tested in two studies, called PHYOX2 and PHYOX8. PHYOX2 included people who were 6 years of age or older, while PHYOX8 included people between 2 and 12 years of age. Both studies looked at different outcomes that helped show how the oxalate levels in the urine (pee) changed over time after people started using Rivfloza. Because high levels of oxalate in the urine can cause and worsen kidney problems, the researchers wanted to see if Rivfloza helped to lower oxalate levels. More details about each of the PHYOX studies are described below.
PHYOX2
In the PHYOX2 study, people were either treated with Rivfloza (with the dose given based on how much each person weighed) or a placebo containing no medicine once a month for six months. The median (middle) age of people in PHYOX2 was 20 years old. About half were female, and half were male. Most (71%) were White, 17% were Asian, 3% reported having multiple races, and race information was missing for about 9% of people. About 60% of people in the PHYOX2 study were also taking another treatment that is commonly used for PH1 called pyridoxine.
PHYOX8
In the PHYOX8 study, everyone got Rivfloza. The median age of people in the study was 5 years. About 33% were female, and the rest were male. Most (80%) were White, and the remaining 20% of people in the study were classified as “non-White” (this was the wording used by the researchers in their report).
What Did the Studies Find?
In both the PHYOX2 and PHYOX8 studies, children and adults with PH1 who received monthly doses of Rivfloza saw large reductions in urine oxalate levels. This shows that the medicine works to lower oxalate levels, which can cause and worsen kidney problems in people with PH1.
Your results may differ from what was seen in clinical studies.
What Is Known About the Effectiveness of Rivfloza Beyond Six Months?
People who were enrolled in PHYOX2, PHYOX8, or other clinical studies of Rivfloza were able to continue treatment in a longer-term study, called PHYOX3. Early results from the PHYOX3 study showed that people who were treated with Rivfloza for an additional six months after the PHYOX2 and PHYOX8 studies continued to have lower oxalate levels in their urine. After two years of treatment with Rivfloza, most people from PHYOX2 reported that their kidney function did not worsen. These findings suggest that long-term reduction of urine oxalate levels with Rivfloza may help prevent kidney damage in people with PH1.
Your results may differ from what was seen in clinical studies.
How Long Until Rivfloza Starts to Work?
In clinical studies of Rivfloza, lower urine oxalate levels were seen at the first visit, which took place 30 days after the first dose. You may not notice if the medicine is working, but it is meant to lower your oxalate levels and keep them lowered over time. This can lower your chance of forming calcium oxalate stones in your kidneys and other areas of your body.
Your results may differ from what was seen in clinical studies.
How Can I Prevent and Manage Side Effects of Rivfloza?
The most common side effect of Rivfloza is injection site reactions, which include pain, redness, bruising, rash, or formation of a dimple where Rivfloza is injected. These injection site problems are usually mild. Also, they did not cause anyone to stop using Rivflova in clinical studies.
Tips to help prevent or ease injection site reactions:
- It is important to take the medicine out of the refrigerator 30 minutes before your injection. Allowing Rivfloza to come to room temperature before you inject it can help lessen pain from the injection.
- Ask your health care provider for ways to lessen discomfort. They may suggest using an ice pack on the area, or they may tell you to gently massage the area.
- Ask your health care provider if an over-the-counter (OTC) pain medicine or antihistamine may help. They can tell you if you can safely take an OTC medicine and when to take it to help ease any pain, itching, or irritation you may have at the injection site.
Getting Your Medicine: What to Expect
You will receive Rivfloza from a specialty pharmacy. The drugmaker has a Patient Support Program to help support the process for you and your health care provider. You can find out more at www.novocare.com/ph1/home.html or by calling 844-906-5099.
Insurance approval. Your insurance may require special approval to cover this medicine, also called a prior authorization. The insurance company reviews the prescription from your health care provider to make sure it is covered.
Cost support. There is a cost support program from the drugmaker that may allow you to pay as little as $0 for your prescription. For questions or more information, contact the drugmaker at 844-906-5099 or visit novocare.com/ph1/savings-offer.html.
