EU Approves Pixantrone for Non-Hodgkin’s B-Cell Lymphomas

Pixantrone (Pixuvri, Cell Therapeutics) has received conditional marketing authorization from the European Commission as monotherapy for the treatment of adults with multiply relapsed or refractory aggressive non-Hodgkin’s B-cell lymphomas (NHL).

The drug is the first approved treatment in the European Union (EU) in this patient setting.

As part of the conditional marketing authorization for pixantrone, Cell Therapeutics will be required to complete a postmarketing study to confirm its clinical benefit.

According to the company, it will make pixantrone immediately available in the EU through a “named patient program,” and will conventionally market the drug in the second half of this year.

Pixantrone “is a welcome addition in our efforts to control disease progression in these late-stage aggressive NHL patients, as it has demonstrated a significant benefit compared to standard treatments used at this stage of disease. By addressing this unmet need, [pixantrone] adds an important treatment option for patients,” said Norbert Schmitz, MD, PhD, from the Department of Hematology at the Askelepios Klinik St. Georg in Hamburg, Germany, in a press statement from the company.

The conditional approval comes only 2 months after pixantrone received a positive opinion from the European Committee on Medicinal Products for Human Use.

The agent has not fared as well in the drug approval process in the United States.

In January, the company withdrew its New Drug Application from the US Food and Drug Administration (FDA), saying it needed additional time to prepare for a second review by the FDA Oncologic Drugs Advisory Committee (ODAC). In 2011, the ODAC rejected the drug and requested further data.

Pixantrone is described by the manufacturer as a novel anthracycline-like product, but with structural differences and modifications that give it enhanced antilymphoma activity and a reduced propensity for acute cardiotoxicity.

The conditional approval of pixantrone in the EU is based on the results of a phase 3 study showing that a greater proportion of patients with relapsed aggressive B-cell NHL achieved a complete response or unconfirmed complete response to pixantrone than patients receiving gemcitabine/rituximab (20% vs 6%). Patients receiving pixantrone also had superior progression-free survival (10.2 vs 7.6 months).

Cell Therapeutics reported that the most frequent adverse effect seen in the clinical studies was suppression of bone marrow, resulting in low levels of white blood cells, platelets, and red blood cells.

According to the company, a summary of product characteristics, which includes full prescribing information, will be posted to the European Medicines Agency Web site in the next few weeks.

One vial of pixantrone contains 29 mg of the agent; it must be reconstituted and diluted before use. The recommended dose is 50 mg/m² on days 1, 8, and 15 of each 28-day cycle for up to 6 cycles. The dose has to be adjusted before the start of each cycle on the basis of nadir hematologic counts or maximum toxicity from the preceding cycle of therapy.

There are many subtypes of NHL, but aggressive B-cell NHL is the most common. Initial therapy for aggressive NHL with anthracycline-based combination therapy cures up to 60% of patients. Of the remaining patients, approximately half will respond to intensive second-line treatment, and some are cured with stem cell transplantation.

Until pixantrone, there has been no drug approved for patients who further fail to respond or who relapse.