In the Phase 3 PANTHER clinical trial, also known as the Pevonedistat-3001 study, researchers were evaluating pevonedistat in conjunction with azacitidine for patients with acute myeloid leukemia (AML), myelodysplastic syndromes (MDS), and chronic myelomonocytic leukemia (CMML). During the trial, researchers sought to understand the efficacy of this combination compared to just azacitidine as a first-line therapy. But according to The Pharma Data, pharmaceutical and biopharma company Takeda Pharmaceuticals (“Takeda”) shared that the trial did not meet its primary endpoint (event-free survival).

Pevonedistat

To begin, what exactly are pevonedistat and azacitidine? Azacitidine is a type of chemotherapy drug, usually administered as an injection. In a prior press release, Takeda described pevonedistat as:

a first in class NEDD8-activating enzyme (NAE) inhibitor. In pre-clinical studies, the inhibition of NAE by pevonedistat blocked the modification of select proteins, which resulted in disruption of cell cycle progression and cell survival, leading to cancer cell death.

Previously, pevonedistat received Breakthrough Therapy designation from the FDA. Within the Phase 3 PANTHER trial, researchers wanted to understand whether the treatment could improve patient outcomes compared to azacitidine alone. However, the trial failed to show that the treatment improved event-free survival, which is survival without the condition proceeding (for example, MDS to AML) or death.

While Takeda is disappointed with the results, the company plans to review the data and determine how to move forward.

Myelodysplastic Syndromes (MDS)

Myelodysplastic syndromes (MDS) refers to a group of progressive conditions which stop the bone marrow from producing enough healthy red blood cells, white blood cells, and platelets. In patients with MDS, these cells are immature, never leaving the bone marrow or dying early. Altogether, there are five MDS subtypes: refractory anemia, refractory anemia with excess blasts, refractory anemia with sideroblasts, refractory anemia with excess blasts in transformation, and chronic myelomonocytic leukemia (CMML). MDS commonly affects older individuals (60+) and affects males more than females. In around half of all diagnoses, MDS progresses to become AML. MDS symptoms include:

• Anemia (low red blood cell count)
• Neutropenia (low white blood cell count)
• Thrombocytopenia (low platelet count)
• Frequent infections
• Chest pain
• Easy bruising and bleeding
• Shortness of breath
• Pale skin
• Heart palpitations
• Fatigue and general malaise

Chronić Myelomonocytic Leukemia (CMML)

While doctors believe there could be an underlying genetic cause for chronic myelomonocytic leukemia (CMML), the truth is that the cause is not yet known. CMML, a rare blood cancer which begins in the bone marrow and then spreads to blood cells, often affects older individuals (60+), those with prior cancer treatments, and males more than females. Symptoms include:

• Appetite loss
• Abdominal pain or pressure
• Enlarged liver and spleen
• High monocyte count
• Fever
• Unintended weight loss
• Anemia (low red blood cell count)
• Frequent infections
• Easy bruising and bleeding
• Fatigue
• Pale skin
• Shortness of breath

Acute Myeloid Leukemia (AML)

Also sometimes referred to as acute myelogenous leukemia, AML is a blood and bone marrow cancer. DNA damage to developing cells causes the formation of abnormal platelets, red blood cells, and myeloblasts (white blood cells). These leukemic cells crowd out healthy cells, causing health issues. Radiation and chemical exposure increase the risk of developing AML. Symptoms include:

• Fever
• Lethargy
• Fatigue
• Pallor (pale skin)
• Easy bruising and bleeding
• Shortness of breath
• Bone pain
• Recurrent infections