Nilotinib (Tasigna) to beat myeloid leukemia drug Glivec (imatinib) coming

Nilotinib (Tasigna) could beat the widely popular Glivec (imatinib) in the treatment of chronic myeloid leukemia.

Nilotinib (Tasigna) showed superior efficacy over Glivec (imatinib) in the treatment of adult patients with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) in chronic phase, according to a Novartis release.

Both the drugs – nilotinib (Tasigna) and Glivec (imatinib) are oral pills developed by the Swiss drug major Novartis.

Tasigna is a selective inhibitor of the Bcr-Abl protein that causes production of cancer cells in Ph+ CML.

Following initial reports of resistance in the Glivec registration trials, Novartis scientists created Tasigna, just a year after the launch of Glivec.

The first clinical trials began just 21 months after discovery. The drug received its first regulatory approval in the second-line indication in 2007.

In a head-to-head comparison of nilotinib (Tasigna) and Glivec (imatinib) as initial treatment for this life-threatening blood cancer, Tasigna results showed statistically significant improvement over Glivec in every measure of efficacy, including major molecular response (MMR), complete cytogenetic response (CCyR) and prevention of progression to accelerated or blastic phase, Novartis announced while presenting the data at the 51st annual meeting of the American Society of Hematology (ASH), held in December, in New Orleans, USA.

The clinical trial, Evaluating Nilotinib Efficacy and Safety in Clinical Trials of Newly Diagnosed Ph+ CML Patients (ENESTnd), is a Phase III randomized, open-label, multicenter trial comparing 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. Designed to detect a difference in MMR between Tasigna and Glivec after 12 months of treatment, it is also the first registration study in which molecular traces of a key biomarker specific to Ph+ CML have been used as a primary endpoint for regulatory review.

ENESTnd is being conducted at 220 global sites with 846 patients enrolled. Patients were randomized to receive Tasigna 400 mg twice daily, Tasigna 300 mg twice daily  or Glivec 400 mg once daily.

At 12 months, fewer patients progressed to accelerated or blastic phase on Tasigna 300 mg twice daily than on Glivec 400 mg once daily.

Tasigna was also well tolerated in patients.

“The outstanding rates of response observed with Tasigna, combined with the very low rate of disease progression, strongly indicate that patients who begin their treatment with Tasigna may have long-term improvement of progression-free survival,” said Giuseppe Saglio, University of Turin, San Luigi Hospital, Orbassano-Torino, Italy, a member of the study management committee.

Novartis now plans to file worldwide applications for approval of Tasigna as a treatment for adult patients with newly diagnosed Ph+ CML.

Tasigna is currently approved in more than 80 countries including the European Union, United States and other countries for the treatment of adult patients with Ph+ CML in chronic phase or accelerated phase who are resistant or intolerant to prior treatment including Glivec.

What is Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML)?

CML is a disease in which the body produces cancerous white blood cells. Almost all patients with CML have an abnormality known as the Philadelphia chromosome, which produces a protein called Bcr-Abl. Bcr-Abl causes malignant white blood cells to proliferate. Worldwide, CML is responsible for approximately 10% to 15% of all adult cases of leukemia, with an incidence of one to two cases per 100,000 people per year.

Glivec is currently 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 tumors (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 tumors. In the EU, Glivec is also approved for the treatment of adult patients with newly diagnosed Ph+ acute lymphoblastic leukemia (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 elodysplastic/myeloproliferative diseases. Glivec is also approved for hypereosinophilic syndrome and/or chronic eosinophilic leukemia.

Headquartered in Basel, Switzerland, Novartis Group offers a diversified portfolio to best meet these needs: innovative medicines, cost-saving generic pharmaceuticals, preventive vaccines, diagnostic tools and consumer health products. In 2008, the Group’s continuing operations achieved net sales of USD 41.5 billion and net income of USD 8.2 billion. Approximately USD 7.2 billion was invested in R&D activities throughout the Group.