Cell Therapeutics, Inc. (CTI), a biopharmaceutical company, has announed that the National Institute for Health and Care Excellence (NICE), a non-departmental public body of the Department of Health in the United Kingdom, has issued a second draft guidance on the use of  Pixuvri (pixantrone) as a monotherapy for the treatment of adult patients with multiply relapsed or refractory aggressive B-cell non-Hodgkin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 draft final appraisal document (FAD) does not recommend funding of pixantrone (Pixuvri) by the UK's National Health Service (NHS). The FAD is open to appeal until July 11, 2013, and any appeal received will be considered by the independent committee of experts during the next stage of guidance development, in accordance with the process set out by NICE.

In addition, CTI in coordination with NICE's Patient Access Scheme Liaison Unit (PASLU) has reached agreement with the UK's Department of Health on a patient access scheme and is applying for rapid reappraisal by NICE. These schemes involve innovative pricing agreements designed to improve cost effectiveness and facilitate patient access to specific drugs or other technologies.

"Our intention is to continue to work with NICE to provide support for Pixuvri as an important therapy for what we believe is an unserved patient population and for whom Pixuvri represents the first pharmaceutical product approved specifically for patients with aggressive B-cell NHL who have failed 2 or 3 prior lines of therapy," said James A Bianco, MD, president and CEO of CTI. "The overall data from the pivotal phase III PIX301 clinical trial demonstrated a favorable benefit-to-risk ratio. We believe continued support among UK lymphoma experts, the data in the labeled population of patients with aggressive B-cell NHL who failed 2 or 3 prior lines of therapy, and the recent approval of a patient access scheme by the Department of Health in England and Wales demonstrates our commitment to bringing this new approved therapy to patients with aggressive NHL in the third line salvage setting."

"There are no other licensed products for use in the 3rd or 4th line," said Professor Finbarr E Cotter, professor of Haematology and chair of Experimental Haematology, Centre for Haemato-Oncology, Barts Cancer Institute. "As a representative for the British Society for Haematology, I feel it is important for NICE to approve pixantrone to make it available with clear guidance for its licensed indication only by haemato-oncologists in England for the small number of unfortunate patients when the opportunity for potentially curative stem cell transplantation is still a possibility if a complete response is achieved".

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 utilising agents in the comparator arm that have anti-tumour 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.

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 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.

CTI is a biopharmaceutical company committed to the development and commercialization of an integrated portfolio of oncology products aimed at making cancer more treatable.