Ninlaro® (ixazomib)

NINLARO (ixazomib) is a prescription medicine used to treat multiple myeloma in combination with the medicines REVLIMID® (lenalidomide) and dexamethasone, in people who have received at least one prior treatment for their multiple myeloma.

Ixazomib was granted orphan drug designation in MM in both the U.S. and Europe in 2011, and for AL amyloidosis in both the U.S. and Europe in 2012. Ixazomib received Breakthrough Therapy status by the U.S. Food and Drug Administration (FDA) for relapsed and/or refractory AL amyloidosis in 2014. It is also the first oral proteasome inhibitor to enter Phase 3 clinical trials.

Four global Phase 3 trials are ongoing: TOURMALINE-MM1, investigating ixazomib vs. placebo in combination with lenalidomide and dexamethasone in relapsed and/or refractory MM; TOURMALINE-AL1, investigating ixazomib plus dexamethasone in patients with relapsed or refractory AL amyloidosis; TOURMALINE-MM2, investigating ixazomib vs. placebo in combination with lenalidomide and dexamethasone in patients with newly diagnosed MM; and TOURMALINE-MM3, investigating ixazomib vs. placebo as maintenance therapy in patients with newly diagnosed MM following induction therapy and autologous stem cell transplant.

For additional information on the ongoing Phase 3 studies please visit www.clinicaltrials.gov.

For more information about NINLARO please visit www.NINLARO.com

General Information

Ninlaro website

NINLARO® (ixazomib) is the first and only oral medication of its kind, a proteasome inhibitor, that you can take at home. A study showed that adding NINLARO to REVLIMID® (lenalidomide) and dexamethasone improved median progression-free survival (PFS) by nearly 6 months (20.6 months with the NINLARO regimen and 14.7 months with the placebo regimen).

Ninlaro 1Point    

At Takeda Oncology, we are committed to helping you get access to NINLARO® (ixazomib) whenever possible. NINLARO 1Point offers comprehensive programs that can assist with the financial concern, cost, and other day-to-day needs associated with your NINLARO treatment.

Understanding Ninlaro

Ninlaro is the first oral proteasome inhibitor approved by the FDA to treat multiple myeloma. It is the third drug in the proteasome inhibitor class that has been approved for MM. Ninlaro is indicated for myeloma patients who have received at least one prior therapy.  

Ninlaro Tip Card 

This handy tip card includes indications, dosage, and potential side effects.        

Possible Side Effects

Thromocytopenia (low platelet count)

Thrombocytopenia is a lowered level of platelets in the blood. Platelets help blood to clot; fewer platelets can lead to bruising, bleeding, and slower healing. Both Ninlaro and Revlimid can cause platelet counts to drop. During treatment with Ninlaro + Revlimid + dexamethasone, the platelet count reaches its lowest point on days 14–21 of each 28-day cycle, but usually recovers to baseline by the beginning of the next cycle. (That is why there is no Ninlaro dose during week four of each cycle.) 78% of the patients in the Ninlaro arm of the TOURMALINE trial and 54% of the patients in the placebo arm had thrombocytopenia, some of it severe enough to be life-threatening.

Diarrhea 

In the TOURMALINE trial, 42% of the patients in the Ninlaro/Rev/dex arm and 36% in the placebo arm (Rev/dex without Ninlaro) experienced diarrhea. While no patient on the trial had diarrhea that was life-threatening, 6% of the cases in the Ninlaro arm and 2% of the cases in the placebo arm were severe.

Constipation

Prevention is the key to managing constipation, which is defined as having fewer than three bowel movements a week. Chronic constipation is defined as infrequent bowel movements or difficult passage of stools that persists for several weeks or longer. While 34% of the patients in the Ninlaro arm, and 25% in the placebo arm of the TOURMALINE trial experienced constipation, less than 1% of cases in either arm were considered serious. Sometimes constipation is the flip side of diarrhea, with patients cycling back and forth between these two uncomfortable states. Talk to your healthcare providers about strategies to regulate your bowel health.

Nausea and vomiting

Nausea affected 26% and 21% of the patients in the Ninlaro and placebo arms of the TOURMALINE trial, respectively, and vomiting occurred in 22% and 11%, respectively. None of these episodes was life-threatening.

Peripheral neuropathy

Peripheral neuropathy (PN) is a serious condition in which treatment affects nerves in the hands, feet, legs, and/or arms. Symptoms of PN include numbness, tingling, cramping, burning, weakness, or pain in the hands, feet, legs, and/or arms. Some patients may have experienced PN from the effects of the myeloma itself and/or from previous treatments for myeloma. If you begin taking Ninlaro with peripheral neuropathy as a pre-existing condition, it is especially important that you pay attention to any increase in your discomfort. Report a worsening of your condition to your doctor immediately. If detected and managed appropriately, your neuropathy should not become worse. If these signs and symptoms are new to you, dealing with them promptly may prevent them from becoming a long-term problem. 28% of the patients on the Ninlaro arm of the TOURMALINE study reported PN, 18% of it mild enough not to cause pain or affect the activities of daily living (grade 1 on a scale of 1–4). In the Revlimid + dexamethasone + placebo arm, 21% reported PN, of which 14% was grade 1. Only 2% of patients in either arm of the study reported PN that caused severe pain, weakness, or numbness that interfered with the activities of daily living.

Peripheral edema

Peripheral edema is accumulation of fluid that causes swelling, usually in the ankles, feet, and legs. This swelling is the result of the accumulation of excess fluid under the skin in the spaces within the tissues, or “interstitial” spaces. Peripheral edema can be a side effect of long-term use of anti- inflammatory medications (such as the corticosteroid dexamethasone), which increase fluid pressure from sodium and water retention, and thereby upset the balance of inflow and drainage of intersti-tial fluid. Peripheral edema can also result from many other causes, including immobility, obesity, varicose veins, cardiac, kidney, or liver dysfunction, gastrointestinal disorders, medications for diabetes such as insulin and pioglitazone, and non-steroidal anti-inflammatories such as ibuprofen and naproxen. Usually peripheral edema affects both legs/ankles/feet. If you have swelling in one leg only, you should tell your healthcare team immediately, as it might signal the presence of a blood clot.

Rash

Rash was reported in 19% of patients in the Ninlaro regimen and 11% of the patients in the placebo regimen in the TOURMALINE trial. The majority of these cases were mild, and fewer than 1% of the patients in either arm discontinued one or more of the three drugs because of a skin reaction. However, rash can be a serious concern. It is potentially dangerous, as a rash may be mild initially and then escalate in severity. Drug rashes vary in severity from mild redness with tiny bumps over a small area to peeling of the entire skin. Rashes may appear suddenly within minutes after a person takes a drug, or they may be delayed for hours or days.

Liver toxicity (hepatotoxcicity)

Drug-induced liver injury was reported in 6% of patients treated with Ninlaro and 5% of the patients treated with placebo in the TOURMALINE study. Signs of liver toxicity include yellowing of your skin or the whites of your eyes and/or pain in your right upper-stomach area.

Eye disorders

Eye disorders of different types were reported in 26% of the patients in the Nin-laro regimen and 16% of the patients in the placebo regimen of the TOURMALINE clinical trial. The most common disorders were blurred vision, dry eye, and conjunctivitis (pinkeye), an inflammation of the thin, clear tissue that lies over the white part of the eye. 2% of the patients in the Ninlaro arm and 1% of the patients in the placebo arm had more serious eye  side effects.

Fetal harm

Based on findings with animals, Ninlaro can cause fetal harm when administered to a pregnant woman. There are no adequate or well-controlled studies in pregnant women, but studies in rats and rabbits that were exposed to the medication at slightly higher levels than those observed in patients caused embryo-fetal toxicity. Women of childbearing potential should not become pregnant while taking Ninlaro. Animal studies indicated that there were no effects due to Ninlaro on male or female reproductive organs.

Clinical Trials

NCT02181413:  A Study of Oral Ixazomib Citrate (MLN9708) Maintenance Therapy in Patients with Multiple Myeloma Following Autologous Stem Cell Transplant

In this phase III study, patients who have had any type of positive response to induction therapy followed by high-dose therapy with stem cell transplant will be randomly assigned by a computer to receive either a placebo (a capsule that looks like ixazomib but has no active ingredient) or ixazomib, an oral proteasome inhibitor, as maintenance therapy. This is a double-blind study, meaning that neither the patient, nor the caregiver, nor the doctor, nor those who evaluate the trial outcome know if the patient is receiving ixazomib or placebo.

Read the Clinical Trial Fact Sheet:      English       Japanese      Korean      French

NCT01850524:  Ixazomib Plus Lenalidomide and Dexamethasone Versus Placebo Plus Lenalidomide and Dexamethasone in Adult Patients with Newly Diagnosed Myeloma

A phase III multicenter study in which patients are randomly assigned by a computer to receive either a placebo (a capsule that looks like ixazomib but has no active ingredient) plus lenalidomide and dexamethasone, or ixazomib (an oral proteasome inhibitor) plus lenalidomide and dexamethasone. This is a double-blind study, meaning that neither the patient, nor the caregiver, nor the doctor, nor those who evaluate the trial outcome know which treatment regimen the patient is receiving. This trial is for patients with newly diagnosed myeloma who are not eligible for stem cell transplant.

Read the Clinical Trial Fact Sheet:      English       Japanese      Korean      French

NCT02046070:  The Oral Combination of Ixazomib with Cyclophosphamide and Dexamethasone in Patients with Newly Diagnosed or Relapsed and/or Refractory Multiple Myeloma

A phase II trial for approximately 148 patients with either newly diagnosed or relapsed and/or refractory myeloma in which response rates and safety of the all-oral combination therapy of ixazomib (an oral proteasome inhibitor), cyclophosphamide (an alkylating chemotherapy agent), and dexamethasone (a synthetic steroid) will be assessed. Newly diagnosed patients will be randomly assigned by a computer to receive one of two different dosing regimens (only the dose of cyclophosphamide will vary), and relapsed/refractory patients will be assigned to a third group.

Read the Clinical Trial Fact Sheet:      English       Japanese      Korean      French

Open Ninlaro clinical trials

ClinicalTrials.gov is a registry of federally and privately supported clinical trials conducted in the United States and around the world. ClinicalTrials.gov gives you information about a trial's purpose, who may participate, locations, and phone numbers for more details. This information should be used in conjunction with advice from health care professionals.