CTI BioPharma Corp, a biopharmaceutical company, focussed on the acquisition, development and commercialisation of novel targeted therapies, has received approval from the Israeli Ministry of Health (MOH) for Pixuvri (pixantrone).

Pixuvri in Israel is indicated as monotherapy for the treatment of adult patients with multiply relapsed or refractory aggressive B-cell non-Hodgkin lymphoma (aggressive B-cell NHL) who have received not more than three previous courses of treatment. The benefit of pixantrone treatment has not been established in patients when used as fifth line or greater chemotherapy in patients who are refractory to last therapy.

In Israel, Pixuvri will be distributed and marketed by the Neopharm Group, Israel's second largest pharmaceuticals and health products marketer, once Pixuvri is included in the Israeli National Health Basket of drugs by the MOH.

"The approval of Pixuvri in Israel provides patients with aggressive B-cell NHL who have failed second or third-line therapy a new approved option, where none existed before, that can effectively treat their disease with manageable side effects," said Abraham Avigdor, M.D., Faculty of Medicine at Tel Aviv University, Ramat Aviv, Israel and Division of Hematology and Bone Marrow Transplantation, Chaim Sheba Medical Center, Tel-Hashomer, Israel. "Patients who have relapsed after second-line therapy have a poor survival outcome. It is vital to have additional treatment options available, like Pixuvri, so we can provide these patients the best care possible and help them battle their disease."

"We are pleased to continue to expand the availability of Pixuvri as interest in this new therapy continues to grow," said James A. Bianco, M.D., President and chief executive officer of CTI. "We feel Pixuvri fills an important role in the treatment paradigm for patients with aggressive B-cell NHL, and we are focussed on increasing access to the treatment for as many patients as possible."

Separately, the Dutch Healthcare Authority (NZa) and the healthcare insurance board College voor zorgverzekeringen (CVZ) of the Netherlands have approved funding for Pixuvri as an add-on drug for patients who need a third- or fourth-line treatment option for aggressive B-cell lymphoma. This follows the inclusion of Pixuvri on the HOVON (Haemato Oncology Foundation for Adults in the Netherlands) treatment guidelines, effective June 1, 2014. The inclusion on the Dutch list of reimbursed drugs makes Pixuvri the first registered and reimbursed medicine for the treatment of patients with multiply relapsed or refractory aggressive B-cell NHL in the Netherlands.

Pixuvri is a novel aza-anthracenedione with unique structural and physiochemical properties. Unlike related compounds, Pixuvri forms stable DNA adducts and in preclinical models has superior anti-lymphoma activity compared to related compounds. Pixuvri was structurally designed so that it cannot bind iron and perpetuate oxygen radical production or form a long-lived hydroxyl metabolite both of which are the putative mechanisms for anthracycline-induced acute and chronic cardiotoxicity. These novel pharmacologic properties allow Pixuvri to be administered to patients with near maximal lifetime exposure to anthracyclines without unacceptable rates of cardiotoxicity.

In May 2012, the European Commission granted conditional marketing authorization for Pixuvri as a monotherapy for the treatment of adult patients with relapsed or refractory aggressive B-cell NHL. The benefit of Pixuvri treatment has not been established in patients when used as fifth-line or greater chemotherapy in patients who are refractory to last therapy.

NHL is caused by the abnormal proliferation of lymphocytes, cells that are key to the functioning of the immune system. It usually originates in lymph nodes and spreads through the lymphatic system. NHL can be broadly classified into two main forms aggressive and indolent NHL. Aggressive NHL is a rapidly growing form of the disease that moves into advanced stages much faster than indolent NHL, which progresses more slowly.

There are many subtypes of NHL, but aggressive B-cell NHL is the most common and accounts for about 55 per cent of NHL cases.1 After initial therapy for aggressive NHL with anthracycline-based combination therapy, one-third of patients typically develop progressive disease.2 Approximately half of these patients are likely to be eligible for intensive second-line treatment and stem cell transplantation, although 50 per cent are expected not to respond.2 For those patients who fail to respond or relapse following second-line treatment, treatment options are limited, and usually palliative only.

Similar to accelerated approval regulations in the United States, conditional marketing authorisations are granted in the EU to medicinal products with a positive benefit/risk assessment that address unmet medical needs and whose availability would result in a significant public health benefit. A conditional marketing authorisation is renewable annually. Under the provisions of the conditional marketing authorisation for Pixuvri, CTI will be required to complete a post-marketing study aimed at confirming the clinical benefit previously observed.

The European Medicines Agency's Committee for Medicinal Products for Human Use has accepted PIX306, CTI's ongoing randomised controlled Phase 3 clinical trial, which compares Pixuvri-rituximab to gemcitabine-rituximab in patients who have relapsed after one to three prior regimens for aggressive B-cell NHL and who are not eligible for autologous stem cell transplant. As a condition of approval, CTI has agreed to have available the PIX306 clinical trial results by June 2015.