What Is Akeega, and Why Does It Matter?
Akeega is a dual-action tablet combining two medicines — niraparib and abiraterone acetate — that has been approved by the FDA in combination with prednisone (a steroid medicine) for treating men with prostate cancer that has a harmful or suspected harmful BRCA2 gene mutation and has spread to other parts of the body (metastatic) but still responds to hormone-lowering therapy. An FDA-approved test is used to confirm the specific genetic changes in this type of prostate cancer.
This form of cancer is termed “BRCA2-mutated metastatic castration-sensitive prostate cancer” (mCSPC) and tends to progress faster and have fewer treatment options. Most patients become resistant to hormone-lowering treatment, and the cancer progresses to a more aggressive, incurable stage called metastatic castration-resistant prostate cancer (mCRPC). About 25% of patients with mCSPC have genetic changes like BRCA mutations, which can make the cancer progress about 50% faster and shorten survival.
Niraparib is a type of drug called a PARP inhibitor that works by blocking PARP-1 and PARP-2 enzymes. This prevents the prostrate tumor cells from repairing their damaged DNA, slowing down their growth and eventually destroying them. Abiraterone acetate is a CYP17 inhibitor that works by blocking a specific enzyme required for making male hormones (androgens) in the body. It lowers the levels of androgens circulating in the body, leading to slower growth and spread of prostate cancer cells. When used together, these medicines target prostate cancer cells in two different ways, making the treatment more precise. Prednisone helps reduce side effects from abiraterone and keeps hormone levels balanced, making the treatment safer and easier to tolerate.
Previously approved in 2023 for BRCA-mutated mCRPC, Akeega with prednisone is now also the first FDA-approved precision therapy for BRCA2-mutated mCSPC. This new approval allows the treatment to be started in the earlier stages of the disease before the cancer develops resistance to hormone therapy.
Why Was It Approved?
The FDA approval is based on results from clinical studies which showed that the combination treatment including Akeega, prednisone, and androgen deprivation therapy (ADT) significantly reduced the risk of worsening of cancer in men with BRCA2-mutated mCSPC.
In a study involving 696 patients with mCSPC and DNA repair gene mutations, patients with BRCA2 mutations were randomly assigned to receive either Akeega plus prednisone and ADT or an oral placebo combined with abiraterone acetate, prednisone, and ADT. The results showed that patients receiving Akeega plus prednisone and ADT showed a 54% lower risk of cancer worsening on scans or death compared with those receiving oral placebo combination therapy. The Akeega-based combination therapy also delayed the worsening of symptoms by 59%, showing a clear benefit for this group of patients. In this group, the time before the cancer worsened had not yet been reached, compared with 26 months for those on placebo combination treatment. The benefit was mainly seen in patients with BRCA2 mutations, with lesser beneficial effects seen in those without these mutations. In an interim analysis, 22% of patients on Akeega plus prednisone and ADT had died compared with 34% on oral placebo with abiraterone acetate plus prednisone and ADT.
The most common side effects included low white blood cell and platelet counts, low hemoglobin levels, high or low potassium levels, tiredness, high blood pressure, nausea, muscle and bone pain, respiratory tract infection, irregular heartbeat, high blood bilirubin and creatinine levels, swelling from fluid buildup, and changes in liver and kidney function. Serious side effects happened in about 36% of people who received Akeega, with anemia and pneumonia being the most common. Some people also had high liver enzyme levels, low blood sugar levels (especially if they were taking medicine for diabetes), and problems with their adrenal glands. These side effects were similar to those already known for the individual drugs in Akeega.
Akeega may cause serious side effects including problems in bone marrow called myelodysplastic syndrome, a type of blood cancer called acute myeloid leukemia, or a condition that affects the brain known as posterior reversible encephalopathy syndrome.
What Do I Need to Know?
You take Akeega by mouth once daily along with prednisone on an empty stomach, either one hour before or two hours after eating. Don’t crush or chew the tablets. The dose includes 200 milligrams of niraparib and 1000 milligrams of abiraterone acetate. The amount of prednisone depends on your cancer type (5 milligrams for CSPC). Don’t change the dose or stop taking Akeega or prednisone unless your health care provider tells you to. If you miss a dose of Akeega, take it later on the same day and go back to your usual schedule the next day. Don’t take extra tablets to make up for the missed dose.
If you haven’t had surgery to lower your testosterone levels, you’ll need to keep taking hormone suppressive therapy (like a GnRH analog) while on Akeega. Your health care provider will check your blood counts, liver and kidney function test results, and blood pressure regularly during and after the treatment. Akeega isn’t recommended if you have moderate or severe liver problems and should be used carefully if you have serious kidney issues. It may also affect how other medicines work, especially those processed by certain liver enzymes like CYP2D6.
Before taking Akeega, tell your health care provider about all your medical conditions, especially if you have heart problems or high blood pressure, low potassium levels, liver or kidney disease, adrenal problems, or diabetes or if you are receiving other prostate cancer treatments. If you have diabetes, your blood sugar levels may need closer monitoring. Akeega should not be used with certain cancer treatments like radium Ra 223 unless you’re enrolled in a clinical trial.
Inform your health care provider if your partner is pregnant or may become pregnant as Akeega can harm a fetus; men should use effective birth control during treatment and for four months after the last dose, and women who may become pregnant should handle the tablets with gloves. Tell your provider about all medicines, vitamins, or supplements you take since Akeega can interact with other drugs.
Contact your health care provider right away if you have fever or frequent infections or notice unusual bleeding or bruising; blood in urine or stool; shortness of breath; fast or irregular heartbeat; swelling in your hands, ankles, legs, or feet; dark urine; yellowing of your skin or eyes; weight loss; dizziness or confusion; eye or vision problems; or unusual headaches or seizures. These could be signs of serious side effects.