Oncology: December 2009 Archives
Nilotinib (Tasigna; Novartis) may be poised to become first-line treatment for Philadelphia-chromosome-positive (Ph+) chronic myeloid leukemia (CML), like its sister drug imatinib (Gleevec; Novartis). In a company-funded, open-label, randomized head-to-head phase 3 study, nilotinib treatment produced significantly higher major molecular response* (MMR) rates at 1 year than imatinib in patients with newly diagnosed Ph+ CML. Results of the study were presented Tuesday at the annual meeting of the American Hematology Society (ASH) in New Orleans.
In addition, nilotinib treatment was associated with significantly higher rates of a complete cytogenetic response (CCyR)—the absence of Ph+ cells in bone marrow. All-important survival outcomes were apparently not included in the study, which is ongoing. (Long-term [ie, 60-month] data for first-line imatinib in Ph+ CML indicate an overall survival rate of 89%.)
|
Outcome |
Nilotinib |
Nilotinib |
Imatinib |
|
MMR | |||
|
3 mo, % |
9 |
5 |
1 |
|
6 mo, % |
33 |
30 |
12 |
|
12 mo, % |
44 |
43 |
22 |
|
Overall, % |
57 |
54 |
30 |
|
12 mo in high-risk pts, % |
41 |
32 |
17 |
|
Complete cytogenic response (CCyR) | |||
|
By 6 mo, % |
67 |
63 |
45 |
|
By 12 mo, % |
80 |
78 |
65 |
|
Est. rate of progression to accelerated phase/blast crisis at 12 mo, % |
<1 |
<1 |
4 |
|
Discontinuation due to adverse events or lab abnormalities, % |
7 |
11 |
9 |
Both nilotinib and imatinib are designed to inhibit the tyrosine-kinase portion (ie, the working end) of the abnormal fusion protein, bcl-abl, which is characteristic of Ph+ CML; but nilotinib is a more selective inhibitor than imatinib.
According to the WSJ, Gleevec, which is currently approved for the first-line treatment of Ph+ CML, generated $3.7 billion in sales last year for Novartis. But the drug's patent will expire in 2015. Nilotinib, 400 mg bid, is currently approved for the treatment of chronic- or accelerated-phase Ph+ CML that is resistant to imatinib. The FDA's Orange Book indicates that the patent on nilotinib will expire in 2023. Treatment with either drug costs more than $40,000 per year.
Last month, Kareem Abdul-Jabbar announced that he was diagnosed with Ph+ CML in December of 2008. It has been inferred here that he is or has been treated with imatinib.
N.B.—Trial name is Evaluating Nilotinib Efficacy and Safety in Clinical Trials-Newly Diagnosed Patients, abbreviated ENESTnd.
* Defined by the elimination of bone-marrow cells that carry the disease-defining bcr-abl fusion protein.
