CTI BioPharma, a biopharmaceutical company, and Servier, an independent French pharmaceutical research company, jointly announced that they have entered into an exclusive license and collaboration agreement to develop and commercialise Pixuvri (pixantrone) in a transaction valued at up to €103.0 million (approximately $133.5 million) if all milestones are achieved. Under the agreement, CTI retains full commercialisation rights for Pixuvri in Austria, Denmark, Finland, Germany, Israel, Norway, Sweden, Turkey, the United Kingdom and the US, with Servier having exclusive rights to commercialise Pixuvri in all other countries.
Pixuvri is conditionally approved in the European Union for patients with aggressive B-cell non-Hodgkin lymphoma (NHL) who failed two or three prior lines of therapy. Pixuvri is the first monotherapy treatment option for this patient group and the only therapy licensed for third and fourth line use in aggressive B-cell NHL patients, which includes diffuse large B-cell lymphoma (DLBCL). As of this announcement, Pixuvri was available in 11 countries and has achieved reimbursement decisions under varying conditions in England/Wales, Italy, France, Germany and the Netherlands. Under the terms of the agreement, CTI will receive an upfront payment of €14 million (approximately $18.1 million) and is eligible to receive additional sales, clinical and regulatory milestone payments, as well as royalties on sales, such royalty payments being subject to certain reductions.
"We believe Servier represents the ideal strategic partner to achieve the full potential of Pixuvri, particularly in those regions of the world where CTI does not currently have, or plan to have a presence," said James A. Bianco, M.D., president and chief executive officer, of CTI. "Our two companies share a vision for bringing Pixuvri to patients and believe this collaboration will not only maximize the development, commercialization and market potential of Pixuvri, but will also help accelerate potential development expansion into new indications. We believe Servier's development expense contributions could help us achieve a net positive contribution margin for Pixuvri this year and profitability in 2015 and beyond."
"Servier is conducting a comprehensive chemistry and biology research program in the field of oncology with the aim to develop and bring novel effective therapies to patients with cancer," said Jean Pierre Abastado, Head of the Oncology Therapeutic Innovation Center at Servier. "In addition, Servier has entered into several scientific collaborations with Academic Institutions as well as a number of other partnerships in the field of oncology and hematology. This new partnership will nicely fit within Servier's portfolio by bringing an immediate therapeutic solution for patients suffering from aggressive B-cell non-Hodgkin lymphoma (NHL) who failed two or three prior lines of therapy."
"This partnership around Pixuvri will also enable Servier to build its hemato-oncology capabilities for market access and medical information in many countries, thereby preparing for the arrival of an extensive portfolio of innovative treatments that are currently in clinical development," said Pascal Touchon, vice president Scientific Collaboration and Business development at Servier.
Pixuvri is a novel aza-anthracenedione with unique structural and physiochemical properties. 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.
In May 2012, the European Commission 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. 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.
There are many subtypes of NHL, but aggressive B-cell NHL is the most common and accounts for about 55 per cent of NHL cases. After initial therapy for aggressive NHL with anthracycline-based combination therapy, one-third of patients typically develop progressive disease. Approximately half of these patients are likely to be eligible for intensive second-line treatment and stem cell transplantation, although 50 per cent are expected not to respond. For those patients who fail to respond or relapse following second line treatment, treatment options are limited, and usually palliative only.
Similar to accelerated approval regulations in the United States, conditional marketing authorisations 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 authorisation is renewable annually. Under the provisions of the conditional marketing authorisation 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 randomised 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.