Novartis has received a positive opinion recommending European Union approval of Tasigna (nilotinib), a selective targeted therapy for adult patients with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) in chronic phase.
The Committee for Medicinal Products for Human Use (CHMP) recommended approval of Tasigna in the first-line indication based on a pivotal phase III clinical trial in which Tasigna surpassed Glivec (imatinib) in key measures of treatment efficacy. In the study, Tasigna was found superior to Glivec in achieving higher rates of both major molecular and complete cytogenetic response and in delaying cancer progression. The data were first published in the June 17 issue of The New England Journal of Medicine and were confirmed by 18-month median follow-up data presented at the 2010 annual meeting of the American Society of Clinical Oncology held in June.
"We are glad that the development of Tasigna may result in a potential new treatment option for newly diagnosed CML patients seeking effective means of preventing disease progression," said Alessandro Riva, Global Head, Oncology Development & Medical Affairs, Novartis Oncology. "Following this positive opinion from CHMP, we look forward to working with regulatory authorities to bring Tasigna to clinical use in the first-line setting as soon as possible."
The European Commission generally follows the recommendations of the CHMP and delivers its final decision within three months. The decision will be applicable to all 27 European Union (EU) member states plus Iceland and Norway. In total, approximately 46,000 people in the EU are affected by CML, a life-threatening blood cancer.
The US Food and Drug Administration (FDA) and Swiss health authority Swissmedic have already approved Tasigna for newly diagnosed Ph+ CML. Regulatory submissions are also under way in Japan and worldwide.
Tasigna is a potent and selective inhibitor of the Bcr-Abl protein that causes production of cancer cells in Ph+ CML. It is also active against a broad spectrum of Bcr-Abl mutations associated with resistance to Glivec. The first clinical trials of Tasigna began only 21 months after its discovery, with the drug receiving its first regulatory approval as a second-line treatment in 2007.
Tasigna surpassed Glivec in key measures of treatment efficacy in the pivotal head-to-head trial, Evaluating Nilotinib Efficacy and Safety in Clinical Trials of Newly Diagnosed Ph+ CML Patients (ENESTnd). Tasigna reduced Bcr-Abl faster than Glivec, leading to lower rates of cancer progression even as early as 12 months. Deep reduction of Bcr-Abl, known as a major molecular response, is considered to be a critical therapeutic milestone associated with good long-term outcomes for patients with Ph+ CML. Treatment with Tasigna led to higher rates of both major molecular response and complete cytogenetic response (elimination of the Philadelphia chromosome that is the hallmark of the cancer) compared with Glivec.
The randomized, open-label, multicenter ENESTnd trial compared the efficacy and safety of Tasigna versus Glivec in adult patients with newly diagnosed Ph+ CML in chronic phase. It is the largest global randomized comparison of two oral therapies ever conducted in newly diagnosed Ph+ CML patients in chronic phase.
Results showed that significantly fewer patients progressed to accelerated or blastic phase on Tasigna 300 mg twice daily than on Glivec 400 mg once daily (2 patients vs. 11 patients) with 14 months of median follow-up. Fewer patients discontinued due to adverse events from the Tasigna 300 mg twice daily arm of the study compared to the Glivec 400 mg once daily arm.
Chronic myeloid leukemia is one of the four most common types of leukaemia, responsible for about 15% of all leukaemia cases worldwide.
Tasigna has been approved in more than 80 countries for the treatment of chronic phase (CP) and accelerated phase Ph+ CML in adult patients resistant or intolerant to at least one prior therapy, including Glivec. The effectiveness of Tasigna for this indication is based on confirmed haematologic and unconfirmed cytogenetic response rates. There are no controlled trials demonstrating a clinical benefit, such as improvement in disease-related symptoms or increased survival.
Tasigna is not approved in the EU for the treatment of newly diagnosed Ph+ CML-CP.
Glivec is approved in more than 90 countries, including the US, EU and Japan, for the treatment of all phases of Ph+ CML. Glivec is also approved in the US, EU and other countries for the treatment of patients with Kit (CD117)-positive gastrointestinal tumours (GIST), which cannot be surgically removed and/or have already spread to other parts of the body (metastasized). In the US and EU, Glivec is now approved for the post-surgery treatment of adult patients following complete surgical removal of Kit (CD117)-positive gastrointestinal stromal tumours. In the EU, Glivec is also approved for the treatment of adult patients with newly diagnosed Ph+ acute lymphoblastic leukaemia (Ph+ ALL) in combination with chemotherapy and as a single agent for patients with relapsed or refractory Ph+ ALL. Glivec is also approved for the treatment of adult patients with unresectable, recurrent and/or metastatic dermatofibrosarcoma protuberans (DFSP) who are not eligible for surgery. Glivec is also approved for the treatment of patients with myelodysplastic/myeloproliferative diseases (MDS/MPD). Glivec is also approved for hypereosinophilic syndrome and/or chronic eosinophilic leukaemia (HES/CEL).
The effectiveness of Glivec is based on overall hematological and cytogenetic response rates and progression-free survival in CML, on haematological and cytogenetic response rates in Ph+ ALL, MDS/MPD, on haematological response rates in systemic mastocytosis (SM), HES/CEL, on objective response rates and progression-free survival in unresectable and/or metastatic GIST, on recurrence free survival in adjuvant GIST and on objective response rates in DFSP. Increased survival in controlled trials has been demonstrated only in newly diagnosed chronic phase CML and GIST.