While most of us were enjoying way too much turkey this week, some interesting activity in the world of pharmaceuticals was taking place. Let’s take a peak.
Two studies published in the November 22 issue of the New England Journal of Medicine may offer new hope in the treatment of refractory multiple myeloma (MM). Thalidomide, an immunomodulatory drug, has activity in about one third of patients with relapsed or refractory MM, an effect that is increased when the drug is combined with dexamethasone. However, thalidomide’s toxicity profile often limits its use. Lenalidomide, a derivative of thalidomide, has been a drug of much interest due to the safer side effect profile and increased potency than its parent drug, as seen in phase 1 and 2 trials. Both of the current studies were phase 3, randomized, controlled trials conducted in Europe and the U.S. and Canada, respectively, and sponsored by Celgene. The primary endpoint, time to disease progression, was the same in both trials. Both studies investigated over 300 patients with relapsed or refractory MM treated with either lenalidomide and dexamethasone or placebo and dexamethasone. The results were similar: the time to progression was significantly longer in the lenalidomide group than the placebo group. In addition, a complete or partial response as well as overall survival was significantly improved in the lenalidomide group. Significant adverse events included neutropenia, thrombocytopenia and venous thromboembolism, and occurred at a higher rate in the Lenalidomide group. However, the incidence of the toxicities that often limit the use of thalidomide, such as severe somnolence, constipation, and peripheral neuropathy was less than 10% in both studies. Authors from both trials concluded that lenalidomide plus dexamethasone is superior to placebo plus dexamethasone in patients with relapsed or refractory multiple myeloma. Further studies might investigate whether lenalidomide plus dexamethadone is superior to thalidomide plus dexamethasone in prolonging disease free survival and resulting in fewer drug-limiting toxic side effects.
Almost every media outlet reported on a groundbreaking study published online in Cell this week describing a method by which human fibroblasts can be converted into stem cells by transfecting four transcription factors into the cells. These reprogrammed cells appear to behave very much like stem cells and can differentiate into multiple cell types. Although in the very early stages of development, a “politically correct” stem cell, free from the ethical issues surrounding embryonic stem cells, is an intriguing concept.
Finally, let’s discuss a trial that has yet to be published but is making headlines nonetheless. In the November 21 issue of the New York Times, many cardiologists are asking the question, “Where are the results of the Enhance trial?,” a study completed 2 years ago but whose data is yet to be released. While we know that ezetimibe (brand name, Zetia) and the combination pill of Zetia plus simvastatin (Vytorin) have cholesterol-lowering effects, data from the Enhance trial is intended to give us information on whether these heavily prescribed agents actually have cardioprotective effects. The trial, conducted by Merck and Schering-Plough, intended to show that Zetia and simvastatin would reduce plaque growth in blood vessel walls more than simvastatin alone by measuring the thickness of plaque in the carotid and femoral arteries. The primary endpoint of the trial was originally defined as the amount of plaque at three points in the carotid artery. However, of particular concern is that the companies now report that they have changed the primary endpoint to measuring thickness at just one place in the carotid, and they no longer expect to release any results from the femoral artery data. Altering the primary endpoint will undoubtedly raise questions aabout to the validity of this trial, leaving the question of whether Zetia and Vytorin are actually effective in reducing cardiovascular endpoints unanswered. As these agents are prescribed for almost 800,000 Americans every week, this is particularly concerning. Moreover, the larger question raised is whether the drug industry is sticking to its promises to improve the disclosure of clinical trials.
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