The European Commission has approved an indication extension of arsenic trioxide, marketed as Trisenox, for low to intermediate risk acute promyelocytic leukaemia.

This marks the first time that a form of acute leukaemia can be effectively treated with a regimen that is entirely chemotherapy-free.

The decision by the European Commission, which follows a positive recommendation from the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) on October 13, grants marketing authorization for first line use of arsenic trioxide in the 28 countries of the European Union.

The indication extension is for newly diagnosed low to intermediate risk APL in combination with retinoic acid.

Today’s announcement points to a recognition by the European Commission that treating low to intermediate risk APL with a chemo-free regimen of arsenic trioxide plus retinoic acid can increase survival rates, dramatically reduce the risk of relapse, and help avoid chemotherapy-related side effects, such as the risk of life-threatening infections.

APL is a form of acute myeloid leukemia (AML), a cancer of the blood-forming tissue (bone marrow).

Approximately 5% to 10% of patients initially diagnosed with AML present with the aggressive sub-type of the condition, APL6.

In APL, immature white blood cells called promyelocytes accumulate in the bone marrow.

The overgrowth of promyelocytes leads to a shortage of normal white and red blood cells and platelets in the body, which causes many of the signs and symptoms of the condition.

APL is generally diagnosed in much younger patients than in AML (the median age is approximately mid-40 for APL patients and 67 for AML patients), and can be diagnosed in patients of any age.

Arsenic trioxide, in combination with retinoic acid, has shown a 99% overall survival rate with almost no relapses after more than four years (50 months) of median follow-up.

The APL0406 Intergroup GIMEMA-AMLSG-SAL study was a prospective, randomised, multicenter, open-label, phase III non-inferiority study.

Eligible patients were adults between 18 and 71 years of age with newly diagnosed, genetically proven low- or intermediate-risk APL (WBC at diagnosis ≤ 103 x 109/L).

Overall, 276 patients were randomly assigned to receive ATRA-ATO or ATRA-CHT between October 2007 and January 2013. Of 263 patients evaluable for response to induction, 127 (100%) of 127 patients and 132 (97%) of 136 patients achieved complete remission (CR) in the ATRA-ATO and ATRA-CHT arms, respectively (P = .12).

After a median follow-up of 40.6 months, the event-free survival, cumulative incidence of relapse, and overall survival at 50 months for patients in the ATRA-ATO versus ATRA-CHT arms were 97.3%v 80%, 1.9% v 13.9%, and 99.2% v 92.6%, respectively (P , .001, P = .0013, and P = .0073, respectively).

Post-induction events included two relapses and one death in CR in the ATRA-ATO arm and two instances of molecular resistance after third consolidation, 15 relapses, and five deaths in CR in the ATRA-CHT arm.

Two patients in the ATRA-CHT arm developed a therapy-related myeloid neoplasm.

“Teva is committed to providing wider access to high-quality medicines to ensure more people can benefit from the treatments they need. We’re very pleased by this decision of the European Commission, and we look forward to offering a chemotherapy-free treatment option for all newly diagnosed APL patients,” said Rob Koremans, MD, President & CEO, Teva Global Specialty Medicines.

Welcoming the approval, Francesco Lo-Coco, Professor of Haematology and Head of the Laboratory of Integrated Diagnosis of Oncohematologic Diseases, Department of Biomedicine and Prevention, University of Rome Tor Vergata, Italy said, “This approval by the European Commission is good news for APL patients as we now have access to a cure for an acute leukaemia without using chemotherapy. Moreover, this decision is a very positive endorsement by the European Commission, as it was made based solely on published academic research and studies. From now on, APL patients with non-high risk disease will have access to this chemotherapy-free regimen of Trisenox plus retinoic acid at diagnosis, which has the potential to increase survival rates while minimising side effects associated with chemotherapy.”

Source: BusinessWire