European MAA filing expected this year as company works toward an additional U.S. trial.
Cell Therapeutics (CTI) inked a five-year manufacturing contract for its late-stage non-Hodgkin lymphoma (NHL) treatment pixantrone with Italian CMO NerPharMa. The deal for commercial and clinical trials production of the drug has been finalised just a month after the Italian regulatory authorities cleared the facility for manufaturing pixantrone. NerPharMa is part of Nerviano Medical Sciences.
Pixantrone is currently being prepared for filing in Europe as a treatment for relapsed or refractory aggressive NHL. CTI had hoped that U.S. approval of the drug would have been granted some time in March this year. FDA’s review of the regulatory submission, however, led it to request an additional clinical trial to confirm pixantrone’s safety and efficacy. At the time CTI said it would seek to establish an expanded access program for the drug while the additional study was carried out.
The firm expects the new trial will be of a similar design to the previous Phase III Extend trial PIX 301, which investigated single-agent pixantrone treatment in patients with relapsed or refractory aggressive NHL who failed two or more prior therapies. “We expect enrollment in a follow-up combination therapy study in a similar population could be rapid and occur predominantly within the U.S.,” noted Jack W. Singer, M.D., CMO, in April.
Meanwhile, and also in April, CTI confirmed that European regulatory authority reviewers had responded favorably to the firm’s proposed filing of pixantrone in the EU on basis of the PIX 301 trial in adults. Filing of an MAA is expected during the second half of 2010. During April the EMEA also recommended the firm submit an updated Pediatric Investigation Plan (PIP) for development of the drug against hematologic cancers in children.
The original PIP was submitted in 2009, and just last week CTI confirmed that it had submitted an expanded PIP to the European authorities. The pediatric program will compare pixantrone with doxorubicin in the treatment of lymphoid cancers in pediatric patients aged 6 months to 18 years. “Filing the updated PIP puts us one step closer to completing the MAA submission process,” Dr. Singer points out.
CTI is also looking to expand the potential therapeutic applications of pixantrone to other cancers. In May the firm announced an agreement with the North Central Cancer Treatment Group (NCCTG) to conduct a Phase II study of the drug in patients with HER2-negative metastatic breast cancer who have tumor progression after two or three prior chemotherapy regimens.
Pixantrone dimaleate for injection is a next-generation aza-anthracenedione with a molecular structure similar to other topoisomerse II inhibitors including anthracyline drugs such as doxorubicin, CTI explains. However, the firm adds, ulike other drugs in this class pixantrone is designed to be more effective and less toxic and can be given through a peripheral vein, negating the need for a central implanted catheter.