The Transparency Commission (Commission de la Transparence or CT) of the French National Health Authority (Haute Autorite de Sante or HAS) has granted market access to the Cell Therapeutics Inc's (CTIs) medicinal product Pixuvri (pixantrone) as a monotherapy for the treatment of adult patients with multiply relapsed or refractory aggressive B-cell non-Hodgkin lymphoma (patients with aggressive B-cell NHL who failed 2 or 3 prior lines of therapy).
The next and final step in France's pharmaceutical reimbursement process is inclusion on the list of medicines approved for hospital use and subsequent publication in the Journal Officiel in France, which CTI now intends to pursue.
"The availability of Pixuvri in France means physicians will be able to extend an approved salvage regimen to those patients that fail second line therapy," said Gilles Salles, MD, PhD., Professor of Medicine at the University Claude Bernard Lyon-1 and president of LYSA, the Lymphoma Study Association.
"The data from the pivotal EXTEND study of Pixuvri clearly indicate that this drug is effective in heavily pretreated patients with relapsed or refractory aggressive NHL," commented Bertrand Coiffier, MD, Professor of Haematology at the Department of Haematology, Hospices Civils de Lyon and the University Claude Bernard, Lyon, France.
The CT noted that aggressive NHL is a serious disease and that there are no standard treatments for patients with this stage of disease. All registered pharmaceuticals in France are subjected to an evaluation process known as Evaluation of Therapeutic Benefit (Amelioration du Service Medical Rendu, or ASMR) by the CT, with the resulting evaluation expressed as a classification between 1 and 6. The CT rated Pixuvri at level 5, which allows Pixuvri to be included in the reimbursed drugs list for hospital use. The CT will reassess the ASMR rating for Pixuvri within two years.
"We are pleased to receive the CT's favorable opinion for reimbursement of Pixuvri and look forward to bringing this new approved therapy to patients in France with aggressive NHL," said James A Bianco, MD, president and CEO of CTI.
In May 2012, the European Commission (EC) granted conditional marketing authorization in the European Union (EU) for Pixuvri as a monotherapy for adult patients with multiply relapsed or refractory aggressive B-cell NHL based on the results of the EXTEND, or PIX301, pivotal randomized phase III clinical trial. Pixuvri was made available to patients in eight countries in the European Union in the fourth quarter of 2012, and some patients in other countries have already started to receive the treatment. Prior to the approval of Pixuvri in the EU, there were no approved agents or standard of care in this disease. The PIX301 trial was designed utilizing agents in the comparator arm that have anti-tumor activity in relapsed disease and are typically employed as palliative therapy for these patients.
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 (EC) granted conditional marketing authorization for Pixuvri as a monotherapy for the treatment of adult patients with multiply relapsed or refractory aggressive 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. The Summary of Product Characteristics (SmPC) has the full prescribing information, including the safety and efficacy profile of Pixuvri in the approved indication.
CTI is currently accruing patients into a phase III trial comparing Pixuvri and rituximab with gemcitabine and rituximab in the setting of aggressive B-cell NHL. Pixuvri does not have marketing approval in the United States.
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.
Similar to accelerated approval regulations in the United States, conditional marketing authorizations 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 authorization is renewable annually. Under the provisions of the conditional marketing authorization 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 (the EMA) Committee for Medicinal Products for Human Use has accepted PIX306, CTI's ongoing randomized controlled phase III 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.
CTI is a biopharmaceutical company committed to the development and commercialization of an integrated portfolio of oncology products aimed at making cancer more treatable.