Dasatinib

Dasatinib is used to treat people with chronic myeloid leukemia and people with acute lymphoblastic leukemia who are positive for the Philadelphia chromosome.[5]

Neutropenia and myelosuppression were common toxic effects. Fifteen people (of 84, i.e. 18%) in the above-mentioned study developed pleural effusions, which was a suspected side effect of dasatinib. Some of these people required thoracentesis or pleurodesis to treat the effusions. Other adverse events included mild to moderate diarrhea, peripheral edema, and headache. A small number of people developed abnormal liver function tests which returned to normal without dose adjustments. Mild hypocalcemia was also noted, but did not appear to cause any significant problems. Several cases of pulmonary arterial hypertension (PAH) were found in people treated with dasatinib.[6]

On October 11, 2011 the U.S. Food and Drug Administration (FDA) announced that dasatinib may increase the risk of a rare but serious condition in which there is abnormally high blood pressure in the arteries of the lungs (pulmonary hypertension, PAH). Symptoms of PAH may include shortness of breath, fatigue, and swelling of the body (such as the ankles and legs). In reported cases, people developed PAH after starting dasatinib, including after more than one year of treatment.

Information about this risk has been added to the Warnings and Precautions section of the Sprycel drug label.[7]

Crystal structure[8] (PDB 2GQG) of Abl kinase domain (blue) in complex with dasatinib (red).

The main targets of dasatinib are BCR/Abl (the "Philadelphia chromosome"), Src, c-Kit, ephrin receptors, and several other tyrosine kinases.

Dasatinib was developed by collaboration of Bristol-Myers Squibb and Otsuka Pharmaceutical Co., Ltd,[9] and named for Bristol-Myers Squibb research fellow Jagabandhu Das, whose program leader says that the drug would not have come into existence had he not challenged some of the medicinal chemists' underlying assumptions at a time when progress in the development of the molecule had stalled.[10]

The Union for Affordable Cancer Treatment objected to the price of dasatinib, in a letter to the U.S. trade representative. The average wholesale price in the U.S. is $367 per day, twice the price in other high income countries. The price in India, where the average annual per capita income is $1,570, and where most people pay out of pocket, is Rs6627 ($108) a day. Indian manufacturers offered to supply generic versions for $4 a day, but, under pressure from the U.S., the Indian Department of Industrial Policy and Promotion refused to issue a compulsory license.[4]

Bristol-Myers Squibb justified the high prices of cancer drugs with the high R&D costs, but the Union of Affordable Cancer Treatment said that most of the R&D costs came from the U.S. government, including National Institutes of Health funded research and clinical trials, and a 50% tax credit. In England and Wales, the National Institute for Health and Care Excellence recommended against dasatinib because of the high cost-benefit ratio.[4]

The Union for Affordable Cancer Treatment said that "the dasatinib dispute illustrates the shortcomings of US trade policy and its impact on cancer patients"[4]

In Bangladesh dasatinib is available under the trade name Dasanix by Beacon Pharmaceuticals.

• Summary Basis for Approval from the U.S. Food and Drug Administration Freedom of Information Homepage
• Sprycel Summary of Product Characteristics (from the European Medicines Agency Website) Link dead 12/1/19
• Discovery of N-(2-Chloro-6-methyl-phenyl)-2-(6-(4-(2-hydroxyethyl)-piperazin-1-yl)-2-methylpyrimidin-4-ylamino)thiazole-5-carboxamide (BMS-354825), a Dual Src/Abl Kinase Inhibitor with Potent Antitumor Activity in Preclinical Assays