May 31, 2012
/PRNewswire/ -- Cell Therapeutics, Inc.("CTI") (Nasdaq and MTA: CTIC) today announced that results from its PIX301 phase 3 clinical trial of Pixuvri® (pixantrone) have been published online in The Lancet Oncology. The publication authored by
, M.D., et al, is titled "Phase 3 Trial Comparing Pixantrone Dimaleate with other Chemotherapeutic Agents as a Single-agent, Salvage Treatment in Patients with Relapsed or Refractory Aggressive non-Hodgkin Lymphoma." The results of the PIX301 clinical trial were the basis for conditional marketing authorization of Pixuvri in the European Union ("EU") as monotherapy for the treatment of adult patients with multiply relapsed or refractory aggressive non-Hodgkin B-cell lymphomas ("NHL"). Pixuvri, is the first and only approved treatment in the EU in this patient setting as was announced on
May 10, 2012
The publication and editorial comments are available at http://www.thelancet.com/journals/lanonc/onlinefirst.
"The results of the PIX301 trial support the use of the Pixuvri for these patients and with the recent conditional marketing authorization in the EU we look forward to having this new, novel drug as an option in the EU to address this serious unmet medical need," stated Dr. Pettengell, M.D. of St. George's Hospital, University of London, the lead investigator for the PIX301 trial and lead author on the publication.
"With conditional marketing authorization by the European Commission earlier this month we are currently implementing our launch plan in the EU to provide access to Pixuvri for these patients as soon as possible," said James A. Bianco, M.D., CEO of CTI.
Summary of Published Results
The PIX301 clinical trial was a phase III single-agent trial of Pixuvri for patients with relapsed or refractory, aggressive NHL who received two or more prior therapies and who were sensitive to treatment with anthracyclines. The trial enrolled 140 patients and patients were randomized to receive either Pixuvri or another single-agent drug currently used for the treatment of this patient population and selected by the physician.
The primary endpoint of CR/CRu (Complete Response ("CR")/Complete Response unconfirmed) rate was 20.0% for Pixuvri and 5.7% for comparator (p=0.021) at End-of-Treatment and 24.3% vs. 7.1% (p=0.009) at End-of-Study ("EOS"). ORR (Overall Response Rate) was 37.1% for Pixuvri and 14.3% for comparator (p=0.003) at EOT and 40.0% vs. 14.3% at EOS (p=0.001). Pixuvri patients experienced a 40% reduction in the risk of death or progression, progression free survival, over the two year study observation and follow up period compared to standard chemotherapy (medians: 5.3 months for Pixuvri vs. 2.6 months for comparator, p=0.005, HR=0.60) and a trend for reduction in the risk of death: median overall survival (10.2 months for Pixuvri vs. 7.6 months for comparator, p= 0.25, HR =0.79). The most common grade 3, 4 adverse events in patients treated with Pixuvri were uncomplicated, noncumulative neutropenia (41.2%), leukopenia (23.5%), and thrombocytopenia (11.8%).
About Pixuvri (pixantrone)
Pixuvri is a novel aza-anthracenedione with unique structural and physio-chemical 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, and, because Pixuvri is not a vesicant, allow it to be safely delivered via a peripheral intravenous catheter.
In May 2012 Pixuvri received conditional marketing authorization in the EU as monotherapy for the treatment of adult patients with multiply relapsed or refractory aggressive NHL. 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. 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://ec.europa.eu/health/documents/community-register/html/h764.htm#ProcList.
Pixuvri is currently available in the EU through Named Patient Programs.
Pixuvri does not have marketing approval in the United States.
About Conditional Marketing Authorization
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 EMA's Committee for Medicinal Products for Human Use ("CHMP") 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.
About Non-Hodgkin Lymphoma
NHL is caused by the abnormal proliferation of lymphocytes, cells 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. The World Health Organization's International Agency for Research on Cancer's 2008 GLOBOCAN database most recent estimates state that in EU approximately 74,162 people will be diagnosed with NHL and 31,371 are estimated to die from NHL every year.
There are many subtypes of NHL, but aggressive B cell NHL is the most common and accounts for about 60% of cases. Initial therapy for aggressive NHL with anthracycline-based combination therapy cures up to 60% of patients. Of the remaining patients, approximately half will respond to intensive second-line treatment and some are cured by stem cell transplantation. Of those not eligible for intensive second line therapy and those patients who fail to respond or relapse, until the approval of Pixuvri, no therapeutic has received regulatory approval for this patient group.
About Cell Therapeutics, Inc.
Headquartered in Seattle, CTI is a biopharmaceutical company committed to developing an integrated portfolio of oncology products aimed at making cancer more treatable. For additional information, please visit www.CellTherapeutics.com.
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This press release includes forward-looking statements that involve a number of risks and uncertainties the outcome of which could materially and/or adversely affect actual future results and the market price of CTI's securities. Specifically, the risks and uncertainties that could affect the development of Pixuvri include risks associated with preclinical and clinical developments in the biopharmaceutical industry in general, and with Pixuvri in particular, including, without limitation, the potential failure of Pixuvri to prove safe and effective for the treatment of relapsed or refractory NHL and/or other tumors as determined by the U.S. Food and Drug Administration, that Pixuvri may not be immediately available to patients in the EU, that CTI may not market and commercialize Pixuvri as planned, that patients may experience side effects from Pixuvri other than suppression of bone marrow, that CTI may not be able to complete the PIX306 clinical trial of Pixuvri-rituximab compared to gemcitabine-rituximab in patients who have relapsed after 1 to 3 prior regimens for aggressive B‑cell NHL and who are not eligible for autologous stem cell transplant by June 2015 or at all as required by the EMA or have the results of such trial available by June 2015 or at all, that CTI may not be able complete a post-marketing study aimed at confirming the clinical benefit observed in the PIX301 trial, that the conditional marketing authorization for Pixuvri may not be renewed, CTI's ability to continue to raise capital as needed to fund its operations, competitive factors, technological developments, costs of developing, producing and selling Pixuvri, and the risk factors listed or described from time to time in CTI's filings with the Securities and Exchange Commission including, without limitation, CTI's most recent filings on Forms 10-K, 10-Q and 8-K. Except as may be required by law, CTI does not intend to update or alter its forward-looking statements whether as a result of new information, future events, or otherwise.