MedNous this week opens up with an article on FDA’s revoking the breast cancer indication for Avastin, saying that the decision did not come as a surprise after the FDA’s Oncologic Drugs Advisory Committee (ODAC) in June voted unanimously to have the indication removed. Avastin had been subject to FDA’s accelerated approval process in this indication.
In contrast, BioCentury Extrareports that FDA encouraged Genentech Inc to continue to study the drug in this indication to identify patients who may benefit and also details Genentech’s plans for Avastin in this indication. It also writes that in the previous months, the National Comprehensive Cancer Network (NCCN) continued to recommend Avastin as an option in breast cancer despite the negative ODAC vote.
The In Vivo Blogcomments on the Avastin decision by saying that it introduced some predictability into the accelerated approval regulatory pathway. Companies should continue to use progression-free survival as a surrogate endpoint but not forget to that FDA has some expectations, e.g. for quality of life benefits, and that sponsors should design trials with supportive measures that can themselves turn into additional claims.
BioCentury this week in its cover story reports on the next-generation, interferon-free treatment regimes for HCV which have been in the focus of the recent Liver Meeting of the American Association for the Study of Liver Diseases (AASLD), stating that the new standard of care introduced only this year following the approval of two HCV protease inhibitors, may be supplanted quickly by new regimes that are tailored to virus subtypes and patient populations.
SciBx is focusing on novel small molecule inhibitors of Monoacylglycerol lipase (MAGL), which regulates the levels of several compounds that signal through the endocannabinoid pathway. However, now that researchers have shown that it MAGL inhibitors reduce neuroinflammation, there is increased interest in the industry in these inhibitors. MAGL also is explored as a cancer target as reported by Derek Lowe in its “In the Pipeline” blog.
SCRIP this week deals with plans of the French health ministry to collect more than €290 million for the pharmaceutical industry in 2012 to reduce health care spending. In addition, it reports on plans to widening the tax on pharmaceutical industry promotion.In its editorial, SCRIP focuses on German media trying to scandalize the deaths attributed to Boehringer Ingelheim’s Pradaxa drug (see the akampioneer).
When German pharma company Boehringer Ingelheim on November 12 said that 260 cases of fatal bleeding have been linked to its new stroke prevention pill Pradaxa, the figures were taken up by many media as evidence that Pradaxa dabigatran, which was launched in Europe in September this year, was a dangerous drug.
In a courageous move, Boehringer Ingelheim yesterday released detailed data from the drug safety database, data that are usually submitted to regulatory agencies only.
Now that the figures are out, several media have taken up the issue again to put it into perspective. Hartmut Wewetzer in Der Tagesspiegel writes that every drug inhibiting blood coagulation poses the risk of bleeding. Wewetzer cites Christoph Bode, a heart specialist from University Clinic Freiburg, as saying that Pradaxa is lowering the risk of fatal bleeding in the brain to 25%, which is a superior value compared to vitamin K antagonists such as Marcumar and Warfarin, the therapeutic standard of previous decades.
Wewetzer also features Boehringer’s calculation that – based on current data – Pradaxa each year can prevent 3,490 of 4,500 stroke cases among 100,000 patients with atrial fibrillation, but may cause 230 cases of fatal bleeding. In comparison, Warfarin is causing 330 deaths. Based on the sum total treatment duration of Pradaxa, which amounts to 410,000 patient years since market authorization, Pradaxa is causing 63 fatal cases among 100,000 patients and year, much less than the figures to be expected from the clinical study data.
Martina Lenzen-Schulte in Frankfurter Allgemeine Zeitung (FAZ) states that the figures reported do not constitute a scandal: “For one, it is in the nature of things that application of blood thinners can cause severe and sometimes fatal bleedings. And the bigger the number of patients treated, the more such complications are to be seen. … Second, it has to be asked whether the incidence of fatal bleedings following dabigatran administration is within the expected limits and – more importantly – whether conventional anticoagulants would have performed better.”
In her article “Deadly Speculations” Lenzen-Schulte also makes clear that competitors are often keen to scandalize side effects of novel drugs and mentions Bayer’s cholesterol-lowering drug cerivastatin as an example. Cerivastatin was withdrawn from the market by Bayer in 2001 following reports of fatal rhabdomyolysis. These cases mostly were due to combination with fibrate drugs – despite warnings on the label.
“It amounts to incapacitation, if one believes that patients always have to be dictated what it best for them”, she writes. “It would be better to put one’s cards on the table and let the patient decide what he wants and what not.”
Boehringer Ingelheim certainly has been quick to do just this, so that patients now can make an informed decision.
First signs of future onset of Alzheimer’s disease (AD) can be found already at the age of 14, reports Volker Stollorz in Frankfurter Allgemeine Sonntagszeitung (FAS). Introducing findings by Heiko Braak and Kelly del Tredici from Ulm University, he also points out that AD seems to originate in the Nucleus coeruleus region of the brain stem from which the typical AD clots slowly spread alongside nerve tracts. Stollorz features plans to include members of families with hereditary forms of AD in future clinical trials to test preventive drugs and treatments. Researchers in Germany currently are planning to launch a website and to found a network modeled according to the US “Dominant Inherited Alzheimer Network” (DIAN). Stollorz and his colleague Thomas Liesen also are co-authors of a TV documentary which can be found here for four weeks from July 19, 2011.
Jutta Hoffritz in Die Zeit reports on novel anticoagulants, e.g. Pradaxa by Boehringer Ingelheim, which is already marketed in the US, and similar drugs developed by Bayer Schering, Pfizer and Daiichi Sankyo. The drugs are developed to replace marcumar which carries the risk of severe side effects and is difficult to dose. However, while the new drugs show better efficacy and promise better compliance, Hoffritz cites German medical doctors expressing skepticism because of unknown long term risks and the anticipated high pricing of the drug. Ulrich Schwabe, editor of Arzneiverordnungsreport, a publication known to be very critical about the pharma industry, is quoted with the calculation that treating all eligible patients in Germany with Pradaxa would amount EUR 4.9 billion per year. The calculation is based on the price of the current daily dosis as the drug is already marketed in Germany for the prevention of thrombosis prior to knee and hip replacement surgery.
Christian Heinrich also in Die Zeit features a trend among pharma companies to search for potential applications of their already approved drugs. As an example, he introduces the “Common Mechanism Research” department of Bayer Schering AG, which is systematically studying unusual effects of Bayer compounds to find clues for novel therapeutic applications. Well-known examples of dual use compounds are sildenafil, which was originally developed to treat circulatory disturbance of the heart (now a common drug to treat erectile dysfunction), and aspirin, which was known as a pain killer and only later developed as anti-coagulant.
Christina Hucklenbroich in Frankfurter Allgemeine Zeitung (FAZ) reports on the suspicion that recently observed deaths of cattle in Germany may be caused by Clostridium botulinum bacteria. However, she points out the the jury is still out on whether there is a novel zoonosis called chronic botulism as presence of the toxin in minute amounts in the gut of affected animals is difficult to confirm. In addition, the source of the bacteria detected in some animals has not yet been identified.
Also in FAZ, Hildegard Kaulen reports on novel findings how smoking cigarettes suppresses appetite. Researchers from Yale University, she writes, found a hitherto neglected nicotine receptor in the brain, which influences the neuronal circuit involved in appetite regulation. Once nicotine binds to the receptor, the nerve cells start releasing the neurotransmitter POMC which in turn influences nerve cells regulating satiety feelings.
Nicholas Wade in The New York Times reports on efforts by scientists from Harvard Medical School to introduce hundreds of changes in the genome of E. coli bacteria simultaneously, an effort dubbed by a colleague as as “macho molecular biotechnology”. The alteration of 314 sites is just an intermediate step by George M. Church and Farren J. Isaacs to establish a method by which certain stretches of DNA could be changed just the way a word processor searches and replaces certain words in an entire document in one step. The researchers removed a particular stop codon (T-A-G, or “amber”) and replaced it by another (which works just as well). Now they are planning to also remove the gene recognizing the deleted stop codon and subsequently to reintroduce amber and reassign it a new function, e.g. to incorporate a novel amino acid into the bacterium’s proteins.
The Economistannounces the world’s first “World Cell Race” taking place in August. Cells sent in by various research institutions all over the world will compete against each other in the race to move towards a chemoattractant. The scientists thereby hope to identify genes involved in cell mobility which are known to be important drivers in cancer metastasis as well as wound healing and immune responses.
New Scientist recently featured a series of articles dealing with bacteria (“bugs that break all rules”): Caroline Williams introduces multicellular behavior of socializing bacteria, features bugs that hunt in packs, bacteria large enough to be visible with the naked eye and bacteria with backbones and cell compartments.
And finally, Cinthia Briseno in Der Spiegel reports on studies proving that the internet is changing the way we memorize and learn. The ability to rely on the internet seems to encourage people to make less mental notes of facts they are sure to find in the web with a few keystrokes.
