Date: 2013-05-22
Type of information: Reimbursement
Product name: Pixuvri®
Compound: pixantrone
Therapeutic area: Cancer - Oncology
Action mechanism:
- topoisomerase II inhibitor. Pixuvri® is a novel aza-anthracenedione with distinct structural and physio-chemical properties. Similar to anthracyclines, Pixuvri® inhibits Topo-isomerase II but unlike anthracyclines -- rather than intercalation with DNA – Pixuvri® alkylates DNA -- forming stable DNA adducts with particular specificity for CpG-rich, hyper-methylated sites. These structural differences resulted in significantly enhanced anti-lymphoma activity compared to doxorubicin in preclinical models. In addition, the structural motifs on anthracycline-like agents that are responsible for the generation of oxygen free radicals and the formation of toxic drug-metal complexes have also been modified in Pixuvri® in an effort to prevent the binding of iron and perpetuation of superoxide production -- both of which are the putative mechanism for anthracycline induced acute cardiotoxicity. These novel pharmacologic differences may allow re-introduction of anthracycline-like potency in the treatment of relapsed/refractory diffuse large cell lymphoma without unacceptable rates of cardiotoxicity.
Company: Cell Therapeutics (USA)
Disease: non-Hodgkin’s B-cell lymphoma
Latest news:
- • On July 21, 2014, CTI BioPharma announced that it 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. In Israel, the drug 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.
- 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.
- • On April 29, 2014, Cell Therapeutics has announced the launch of Pixuvri® (pixantrone) in the UK at the 54th annual scientific meeting of the British Society for Haematology. This launch follows conditional marketing authorization by the European Commission in 2012 and the National Institute for Health and Care Excellence final guidance recommending prescription of Pixuvri® as a cost-effective monotherapy in early 2014.
- Pixuvri® is currently available in Austria, Denmark, Finland, Germany, Italy, France, Netherlands, Norway, Sweden and the UK. CTI intends to pursue making Pixuvri® available in other European countries in 2014. 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.
- • On February 27, 2014, Cell Therapeutics 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 UK, has published final guidance recommending prescription of Pixuvri® (pixantrone) as a cost-effective 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. The final guidance determines Pixuvri® cost effective and recommends prescription of Pixuvri® 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, for as long as CTI makes the Patient Access Scheme (PAS) available. The PAS is a confidential pricing and access agreement with the United Kingdom's Department of Health. Publication of the final guidance by NICE follows the final appraisal determination, or FAD, that was issued in January 2014. CTI expects to officially launch Pixuvri® in England and Wales this spring, after the FAD has been largely implemented.
- • On January 6, 2014, Cell Therapeutics has reported that the NICE 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). 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.
- • On December 4, 2013, Cell Therapeutics has announced that it has reached an agreement with the National Association of Statutory Health Insurance Funds (GKV-Spitzenverband) in Germany on the reimbursement price of Pixuvri® (pixantrone). The drug is already available in Germany for healthcare professionals to prescribe in accordance with local guidance.
- • On October 15, 2013, Cell Therapeutics has announced that the NICE issued second draft guidance on Pixuvri® (pixantrone) as a monotherapy for the treatment of adult patients with multiply relapsed or refractory aggressive B-cell non-Hodgkin lymphoma (aggressive B-cell NHL). NICE's independent Appraisal Committee met on September 11, 2013, to consider the cost effectiveness of pixantrone taking into consideration CTI's initial patient access scheme that was approved by the Department of Health in July 2013. The result is a second appraisal consultation document, whereby the Committee concluded that this scheme does not overcome the uncertainties in the evidence for pixantrone's clinical effectiveness and once again requests that consultees, including CTI, healthcare professionals and members of the public, comment on the draft guidance via the NICE website.
- • On August 19, 2013, Cell Therapeutics, has reported that 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 for the medicinal product Pixuvri® 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 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.
- • On July 8, 2013, Cell Therapeutics has announced that the Company has been granted market access by the Italian Medicines Agency (AIFA) for Pixuvri® 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).
- • On May 20, 2013, Cell Therapeutics has reported that Germany's Federal Joint Committee (G-BA) has issued its final benefit assessment report for Pixuvri®, which is indicated as a monotherapy for the treatment of adult patients with aggressive B-cell non-Hodgkin lymphoma (NHL) who have failed two or three prior lines of therapy. The G-BA reported that additional benefit could not be determined for Pixuvri® versus the comparator therapies assigned by G-BA, the ultimate authority in determining reimbursement for drugs in Germany. The Federal Joint Committee also decided that the prescribability for pixantrone should be limited to hematologists and oncologists and that this limitation might be of relevance for the GKV-SV, the Federal Association of Statutory Health Insurance Funds, with regard to the therapy cost, since the cost for Pixuvri® was only marginally higher than the cost of the appropriate comparative therapy.
- • On September 11, 2012, Cell Therapeutics has announced the initiation of the commercial launch of Pixuvri® in the EU with entry into Sweden, Denmark and Finland in September, to be followed by Austria and Norway in early October 2012 and Germany, United Kingdom and the Netherlands in November 2012. CTI plans to expand availability to France, Italy and Spain as well as other European countries in 2013.
- • On May 10, 2012, Cell Therapeutics has announced that it has received conditional marketing authorization from the European Commission for Pixuvri® (pixantrone) as monotherapy for the treatment of adult patients with multiply relapsed or refractory aggressive non-Hodgkin B-cell lymphomas. CTI expects to make Pixuvri® immediately available in the EU, initially through a named patient program.
- CTI plans to market and commercialize Pixuvri® with its own sales force in the EU starting in the 2nd half of 2012. Pixuvri® will be marketed in the EU as Pixuvri® 29 mg powder for concentrate for solution for infusion; and is indicated as 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. One vial of Pixuvri® contains 29 mg pixantrone (as dimaleate), and must be reconstituted and diluted before use.
- • On February 17, 2012, The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended that Pixuvri® be granted conditional approval for the cancer non-Hodgkin’s B-cell lymphoma. The drug is to be used on its own in patients whose cancer is aggressive and has come back after multiple rounds of previous chemotherapy or is not responding to other treatments. The Committee recommended conditional approval, because the data supplied show that its benefits outweigh its risks but are not yet comprehensive, and that more information is needed on the benefits of the medicine in patients who have received rituximab in the past. At the same time, the Committee concluded that Pixuvri® satisfies an unmet medical need, because there are no approved and standard treatments for this stage of the disease. Therefore, the benefits of making this medicine available on the market immediately outweigh the risks inherent in the fact that additional data are required. The main study showed that a greater proportion of patients responded to Pixuvri® than a comparator chemotherapy medicine (20% versus 6%) and that patients receiving Pixuvri® survived for longer without their disease getting worse (an average of 10.2 versus 7.6 months). The Committee also noted that the benefit of Pixuvri® appeared to be lower in patients who had received rituximab in the past, and that its benefit was not established in patients when used as the fifth or later round of chemotherapy in patients whose disease did not respond to the last treatment.
- The conditional approval will be renewed on a yearly basis until the obligation to provide additional data on rituximab-pretreated patients has been fulfilled. CTI Life Sciences has informed the Committee that it expects to be able to provide the results of the additional study by mid-2015. The most frequent side effect seen in the clinical studies was suppression of the bone marrow, resulting in low levels of white blood cells, platelets and red blood cells. Infections were common, but were only serious in a few patients.
Patents:
Submission of marketing authorization application USA :
Submission of marketing authorization application UE:
Withdrawal of marketing authorization application USA:
Withdrawal of marketing authorization application UE:
US authorization:
UE authorization: 2012-05-10 (conditional approval)
Favourable opinion UE: 2012-02-17
Favourable opinion USA:
Orphan status USA:
Orphan status UE:
Pediatric exclusivit _USA:
Pediatric exclusivity UE:
OTC status:
Other news:
Is general: Yes
