Ninlaro

Approved Uses

Ninlaro is approved by the U.S. Food and Drug Administration (FDA) to treat multiple myeloma. This is a cancer that forms in a type of white blood cell called a plasma cell. Healthy plasma cells help you fight infections by making antibodies that recognize and attack germs. In multiple myeloma, cancerous plasma cells accumulate in the bone marrow and crowd out healthy blood cells.

Combination Therapy

Ninlaro is not used as a standalone treatment. It is prescribed as part of a specific three-drug combination for patients who have already tried at least one other treatment for their cancer. The regimen includes:

• Ixazomib (Ninlaro): A proteasome inhibitor that helps block certain proteins in cancer cells, preventing them from growing and spreading.
• Lenalidomide: A medication that helps the immune system work better to fight cancer cells.
• Dexamethasone: A steroid that helps reduce inflammation and can also kill cancer cells.

Because Ninlaro is available in capsule form, it allows patients to receive a proteasome inhibitor treatment orally rather than through intravenous (IV) infusion or injection.

Mechanism of Action

Ninlaro belongs to a class of medications called proteasome inhibitors. It works by targeting and blocking the activity of proteasomes, which are enzyme complexes found in all cells.

The Role of Proteasomes

Proteasomes act like a cellular recycling system or garbage disposal. Their primary job is to break down and remove damaged or unneeded proteins within a cell. This process is essential for maintaining the health and normal function of the cell.

How Ninlaro Affects Cancer Cells

When Ninlaro blocks these proteasomes, the proteins that should have been broken down begin to build up inside the cell. This accumulation of protein becomes toxic, eventually triggering a process that leads to cell death. While this can affect healthy cells, cancer cells—specifically multiple myeloma cells—are often more sensitive to this process because they produce proteins at a much higher rate than normal cells. By disrupting this balance, Ninlaro helps to:

• Stop the growth and spread of cancer cells.
• Induce programmed cell death, also known as apoptosis, in the tumor.
• Reduce the overall number of cancer cells in the body.

Common Side Effects

• Diarrhea or constipation
• Nausea and vomiting
• Swelling of the hands, feet, or ankles
• Back pain
• Skin rash

Serious Side Effects

Some side effects can be severe and require immediate medical attention. These include:

• Low blood cell counts: Ninlaro can cause a decrease in platelets (thrombocytopenia) and white blood cells (neutropenia), which may lead to increased bleeding, bruising, or infections.
• Nerve damage: Peripheral neuropathy may cause numbness, tingling, or burning pain in the hands and feet.
• Liver toxicity: Symptoms may include yellowing of the skin or eyes (jaundice), dark urine, or pain in the upper right stomach area.
• Severe skin reactions: Seek medical help for a widespread rash, blistering, or peeling skin.
• Severe digestive issues: Persistent or severe diarrhea, nausea, or vomiting.
• Eye problems: Changes in vision, such as blurred vision, dry eyes, or inflammation of the eye.

Blood and Platelet Disorders

Thrombocytopenia, or a low level of platelets in the blood, is a common risk. This condition can increase the chance of bruising or bleeding. Healthcare providers typically monitor platelet counts at least monthly during treatment.

Gastrointestinal Complications

Diarrhea, nausea, and vomiting are frequently reported. In some cases, these symptoms can be severe and may lead to dehydration. Medical management or dosage adjustments may be necessary if these issues persist.

Nerve and Tissue Effects

• Peripheral Neuropathy: Some patients experience nerve damage, which may cause numbness, tingling, burning, or pain in the hands and feet.
• Peripheral Edema: Swelling caused by fluid retention in the arms, legs, hands, or feet can occur.

Skin and Liver Health

Rashes are a known side effect and can range from mild to severe. In rare instances, serious skin reactions have been reported. Additionally, Ninlaro can cause liver injury, requiring regular monitoring of liver function through blood tests.

Reproductive Risks

Ninlaro can cause fetal harm when administered to pregnant individuals. Effective contraception is recommended for females of reproductive potential and for males with female partners of reproductive potential during treatment and for a period after the final dose.

Thrombotic Microangiopathy

There have been reports of thrombotic microangiopathy, a condition involving blood clots in small blood vessels, which can be life-threatening and requires immediate medical attention.

Pregnancy

Ninlaro can cause fetal harm when administered to a pregnant woman. Based on animal studies and its mechanism of action, this medication may cause birth defects or pregnancy loss. There are no adequate studies of Ninlaro use in pregnant humans.

Healthcare providers typically recommend the following for patients of reproductive potential:

• Pregnancy Testing: Females should confirm they are not pregnant before starting treatment.
• Contraception for Females: Use effective contraception during treatment and for 90 days after the final dose. Since Ninlaro may interfere with hormonal birth control, a barrier method is often advised.
• Contraception for Males: Men with female partners who can become pregnant should use effective contraception during treatment and for 90 days after the final dose.

Breastfeeding

It is unknown if Ninlaro passes into human breast milk. Because of the risk of serious side effects in a nursing infant, breastfeeding is not recommended during treatment and for 90 days after the last dose. Patients should discuss infant feeding options with their healthcare provider.

Dosage Forms

Ninlaro is available as a capsule for oral administration. The capsules are provided in individual blister packs to protect the medication. Each capsule is color-coded and imprinted with a logo for identification.

• Oral capsule

FDA Approval History

The U.S. Food and Drug Administration (FDA) approved Ninlaro in November 2015. It was the first oral proteasome inhibitor approved for the treatment of multiple myeloma, providing an alternative to injectable treatments in its class.

Approved Indications

Ninlaro is approved for use in combination with the medications lenalidomide and dexamethasone. This combination therapy is intended for adults with multiple myeloma who have already undergone at least one previous treatment regimen.

Regulatory Oversight and Safety

The FDA continues to monitor Ninlaro through its adverse event reporting systems. In 2018, the FDA identified potential signals of serious risks, including severe skin reactions such as Stevens-Johnson syndrome and toxic epidermal necrolysis. These findings led to updates in the drug's safety labeling to inform healthcare providers and patients of these risks. There is currently no Boxed Warning or Risk Evaluation and Mitigation Strategy (REMS) required for this medication.

Factors Affecting Cost

The actual price you pay for Ninlaro can vary based on several factors:

• Insurance coverage: Your out-of-pocket costs will depend on your specific health insurance plan, including deductibles and copayments.
• Pharmacy type: Because Ninlaro is a specialized oncology medication, it is typically dispensed through specialty pharmacies rather than standard retail locations.
• Dosage: The specific strength prescribed for your treatment cycle may influence the total cost.

Generic Availability

Ninlaro is currently only available as a brand-name medication. There is no generic version of ixazomib available at this time, which generally means the cost remains higher than it would be for a generic alternative.

Financial Assistance

Many patients may be eligible for financial support programs. The manufacturer often provides resources such as copay assistance cards or patient assistance programs for those who meet specific clinical and financial criteria. You may also find support through non-profit organizations that assist with cancer treatment costs.