Celgene Expands Vidaza Criteria for Treatment of Acute Myeloid Leukemia

Expansion covers patients who have greater than 30% myeloblasts.

Celgene recently announced that the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) has expanded the criteria for treatment of acute myeloid leukemia (AML) with Vidaza (azacitidine) for patients aged 65 or older who are not eligible for hematopoietic stem cell transplantation (HSCT).

The expansion now covers patients who have greater than 30% myeloblasts when previously it only covered those patients who had 30% or less myeloblasts. Myeloblasts are white cells in the bone marrow and in the instance of AML, their functioning becomes disrupted and results in the presence of numerous non-functioning white cells.

This can interfere with the body’s ability to control infection and can lead to anemia and hemorrhaging. Many patients with AML, especially the older patient population, do not have positive outcomes with their disease and experience rapid deterioration of quality of life.

This is particularly true for patients who cannot tolerate curative therapies like stem cell transplantation.

“Celgene is committed to bringing innovative medicines to patients with hematological diseases including AML,” said Tuomo Pätsi, president of Celgene in Europe, Middle East, and Africa (EMEA). “With the positive CHMP opinion for Vidaza in AML, Celgene has an opportunity to advance the treatment options available to patients with AML. And, we will continue to focus on meeting the unmet needs of patients with myeloid disease, as we have several partnerships and development programs that will build on what we are learning about treating these diseases.”

More than 14,000 patients suffer from AML in Europe and many of those patients will die within less than one year due to the fact that AML progresses rapidly, especially when stem cell transplantation is not an option. For elderly patients, improvements have not been made in patient survival rates for more than 40 years, indicating a strong need for treatments that can support this patient population.

“While progress has been made in treating younger, fitter AML patients who can undergo intensive and potentially curative therapies such as stem cell transplant, there is still a clear need for treatments for elderly and more frail patients,” said Hervé Dombret, MD, Chief Blood Disease Department, University Hospital Saint-Louis, AP-HP, Paris, France. “Azacitidine has demonstrated a median overall survival of 10.4 months, and these results suggest that, if approved, azacitidine could provide a valuable treatment option for patients who have limited options today.”

The CHMP decision came following the results of the AML-001 study, a global, multi-center, randomized, open-label pivotal study that evaluated patients at least 65 years old with newly diagnosed or secondary AML with greater than 30% bone marrow blasts. The study evaluated the safety and efficacy of using Vidaza to treat these patients compared with traditional treatment methods.

The primary endpoint of the study was to increase survival rates, which the researchers did with patients taking Vidaza surviving for an average of 10.4 months versus the 6.5 months for patients receiving traditional treatment. One-year survival rates with azacitidine and conventional treatment regimens were 46.5% and 34.2%, respectively.

Patients in the study experienced side effects including anemia (16%), neutropenia (26%), febrile neutropenia (28%) and thrombocytopenia (24%). However, these rates were significantly higher for treatments with low-dose Ara-Cytarabine and intensive chemotherapy.

In addition to the positive decision by the CHMP, the organization also noted that this new therapeutic indication brings significant clinical benefit in comparison with existing therapies. If the European Commission adopts the decision fully, Vidaza will receive extended market protection in all its expansions for an additional year throughout the European Economic Area. This decision is expected to be set within the next two months.

The decision would make Vidaza available for use in treating myelodysplastic syndromes (MDS) and AML. Vidaza has been approved in the EU since 2008 for the treatment of adult patients ineligible for transplantation diagnosed with intermediate 2 and high-risk MDS, chronic myelomonocytic leukemia with 10 to 29 percent marrow blasts without myeloproliferative disorder, or acute myeloid leukemia with 20 to 30 percent blasts and multi-lineage dysplasia.

The United States has yet to approve Vidaza for treatment of patient with AML, but the drug can be used to treat refractory anemia or refractory anemia with ringed sideroblasts (RARS), refractory anemia with excess blasts (RAEB), refractory anemia with excess blasts in transformation (RAEB-T), and chronic myelomonocytic leukemia.