Cell Therapeutics, Inc. (CTI) has reported that the National Institute for Health and Care Excellence (NICE), the independent body responsible for driving improvement and excellence in the health and social care system in the United Kingdom (UK), has issued its Final Appraisal Determination (FAD) for PIXUVRI(®) (pixantrone). The positive final draft guidance determines PIXUVRI cost effective and recommends funding the treatment as a monotherapy for the treatment of adult patients with multiply relapsed or refractory aggressive B-cell non-Hodgkin lymphoma (aggressive B-cell NHL), which includes diffuse large B-cell lymphoma (DLBCL). CTI estimates that there are approximately 1,600 to 1,800 people in the UK diagnosed with multiply relapsed aggressive B-cell NHL per year.
James A. Bianco, M.D., President and Chief Executive Officer of CTI stated, "The positive recommendation by NICE for the funding of PIXUVRI means that physicians in England and Wales now have access to the only approved therapy for their patients with aggressive B-cell NHL in the third- and fourth-line salvage setting."
The NICE Appraisal Committee reviewed CTI's updated data analysis showing PIXUVRI's cost effectiveness and recommended the treatment as an option for certain people with histologically confirmed aggressive B-cell NHL who have previously received rituximab and are receiving PIXUVRI as a third- or fourth-line treatment.
The FAD further recommends the prescription of PIXUVRI for as long as CTI makes the Patient Access Scheme (PAS) available. The PAS is a confidential pricing and access agreement with the UK's Department of Health.
The FAD forms the basis of the final guidance to the NHS in England and Wales and is expected to be published in February 2014. Once the final guidance is published, the NHS must fully implement it within 90 days. CTI expects to officially launch PIXUVRI in England and Wales in early spring, when the FAD has been largely implemented.
Professor John Radford, a lymphoma expert at The University of Manchester and The Christie NHS Foundation Trust in Manchester - both part of the Manchester Cancer Research Centre said, "DLBCL is the most common type of aggressive NHL and despite undoubted progress over the last 10 years resulting from the introduction of better first-line therapy, the disease still recurs in some patients. The recent recommendation by NICE for the funding of PIXUVRI provides an additional treatment option for these patients and is a welcome development."
Professor Finbarr E. Cotter, Professor of Haematology and Chair of Experimental Haematology, Centre for Haemato-Oncology, Barts Cancer Institute, and representative for the British Society for Haematology (BSH) commented, "The availability of PIXUVRI means physicians will be able to extend an approved salvage regimen to those patients that fail second- or third-line therapy. The data from the pivotal EXTEND Phase 3 trial of PIXUVRI clearly indicate that this drug is effective in heavily pretreated patients with relapsed or refractory aggressive NHL."
About PIXUVRI (pixantrone)
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. The SmPC is available at http://www.pixuvri.eu. PIXUVRI does not have marketing approval in the United States.
NHL is the sixth most common cancer in the UK; in 2010, 12,180 people were diagnosed with the disease.(1) 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 percent of NHL cases.(2) After initial therapy for aggressive NHL with anthracycline-based combination therapy, one-third of patients typically develop progressive disease.(3) Approximately half of these patients are likely to be eligible for intensive second-line treatment and stem cell transplantation, although 50 percent are expected not to respond.(3) For those patients who fail to respond or relapse following second-line treatment, treatment options are limited, and usually palliative only.(3)
About Conditional Marketing Authorization
Similar to accelerated approval regulations in the United States, conditional marketing authorizations are granted in the E.U. 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 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.