On April 2010, Cell Therapeutics received a complete response letter from the FDA stating that the FDA could not approve pixatrone dimaleate (which would have been mareted as Pixuvri) for the treatment of relapsed or refractory aggressive non-Hodgkin's Lymphoma (NHL). The agency requires additional clinical trial to be conducted because efficacy has not been demonstrated in the submitted trials. However, due to limited therapeutic options, the FDA has allowed Cell Therapeutics make the drug available to selected patients while the company plans to conduct further trials to fulfill the FDA's requirement.
- Since April, the company has met the FDA and filed for Special Protocol Assessment (SPA) for pixantrone for the treatment of relapsed or refractory aggressive B-cell Non-Hodgkin's Lymphoma in August 2010. The second registrational trial is called PIX306.
- In June 2010, the company announced the results from its phase III pivotal trial PIX301 using pixantrone dimaleate for the treatment of relapsed or refractory, aggressive non-Hodgkin's lymphoma. The results showed pixantrone was able to increase patients' progression-free survival by 2 months. However, patients' overall survival was not significantly different between the use of pixantrone and its comparators. This can be thought of as pixantrone was not able to extend patients' overall survive more than current therapies.
- From the trial: common sides effects (>10% and grade 3/4): neutropenia and leukopenia. The number of patients experienced grade 3 or greater cardiac events were 5 in the pixantrone group, 4 more than the comparator arm.
Meanwhile, it is a different story on a different shore. After receiving positive opinions from the European Regulatory Authorities and European Pediatric Committee, Cell Therapeutics submitted the Expanded Pediatric Investigation Plan in the EU. In November 2010, Cell Therapeutics finally submitted European Marketing Authorization Application for Pixuvri. The European Medicines Agency has validated the application and the review process has begun. If approved, Pixuvri will be marketable in the European Member States. In addition, the company plans to to submit a marketing application in other selected European countries starting with Switzerland.
So what is Pixantrone?
- Pixantrone is an aza-anthracenedione whose structure is similar to anthracycline like doxorubicin. Anthracyclines are topoisomerase II inhibitors which work to cause double-stranded DNA breakage and lead to cell death. Even though the two share similarities, pixantrone forms stable DNA adducts after alkylating with the FDAs. It targets the CpG rich, hyper-methylated sites. Anthracyclines have been known to cause cardiac toxicity. Pixantrone is also suspected to cause the same adverse event even though pixantrone has been designed to prevent the binding of the drug and iron in addition to prevent the prepetuation of superoxide production. Hence, patients need to be monitored for cardiac toxicity besides other common ones until further trial has been completed and assessed.
- Since May 2009, pixantrone has been available in Europe as an investigational drug on a named-patient basis.