Tasigna — Another good drug for CML

Tasigna was recently (June 17,2010) approved for Philadelphia chromosome positive CML (Chronic Myelogenous Leukemia). You may be aware that CML is an unusual malignancy in that there is just one gene mutation with a number of minor variations–reciprocal translocation between chromosome 9 and 22 designated as t(9;22)(q34;q11). This tranlocation is occasionally found in acute lymphoblastic leukemia and acute myelogenous leukemia.

Having a single target appears to make the disease more susceptible to targeted drug intervention.

BCR-abl activates tyrosine kinase cell division controllers speeding up cell division and ultimately may cause blast crisis through the resulting genetic instability.

In the 90’s imatinib (Gleevec) was identified as active in CML blocking tyrosine kinase inhibitors. While not curative the drug resulted in immediate dramatic improvement in survival for CML patients. Some patients however in time became resistant and there are several newer tyrosine kinase inhibitors on the market that appear to work in these Gleevec resistant patients. Tasigna is one.

This is from the FDA:

The efficacy and safety of nilotinib in adults with newly diagnosed CP-CML was demonstrated in a single randomized, active-control, open-label multinational clinical trial. Eight hundred and forty-six patients were randomized to imatinib 400 mg QD (n = 283), nilotinib 300 mg BID (n = 282), or nilotinib 400 mg BID (n = 281). The primary objective was to compare the rate of major molecular response (MMR) at 12 months of nilotinib 300 mg BID and nilotinib 400 mg BID with that of imatinib 400 mg QD. MMR was defined as a ≤0.1% BCR-ABL/ABL % by international scale measured by RQ-PCR, which corresponds to a ≥3 log reduction of BCR-ABL transcript from standardized baseline. The rate of complete cytogenetic response (CCyR) by month 12 was the key secondary endpoint.

The primary efficacy endpoint, MMR at 12 months, was achieved in 63 patients [22% (95% CI: 18, 28)] in the imatinib arm, 125 patients [44% (95% CI: 38, 50)] in the nilotinib 300 mg BID arm, and 120 patients [43% (95% CI: 37, 49)]

In the nilotinib 400 mg BID arm. The differences were statistically significant

(p < 0.0001) for each nilotinib arm compared to the imatinib arm. CCyR rates by 12 months were 65% (95% CI: 59, 71) for the imatinib arm, 80% (95% CI: 75, 85) for the nilotinib 300 mg BID arm and 78% (95% CI: 73, 83) for the nilotinib 400 mg BID arm.

Medicynical Note: This is an example of a class of drugs, tyrosine kinase inhibitors, that are very effective but very expensive. To control CMS requires continued treatment often for many years at a cost approaching $100,000/year.

To return to a theme, this exceeds our average yearly and median incomes. Charging more for a single item that has become a necessity of life than the great majority of the population earns is unique to pharmaceuticals. Which in a way speaks volumes of our values?

It will be interesting to see if Tasigna is priced more reasonably. Consider that this drug was approved, as was Gleevec after a single clinical trial. And in the case of Gleevec much of the early research funding came from you and me through federal grants. I rather doubt we’ll see responsible pricing.

Drug pricing by any measure in our country is excessive and shows little signs of moderating. Our elected representatives appear to be handsomely rewarded for their support of the industry with large campaign contributions.

We need to look at patents and provide a market based means to reward companies that price drugs reasonably. We need to look at our insurance industry and their lax controls over drug expenditures. Providing cost efficacy studies on all these prohibitively expensive agents would help as well–but who will do them?