Tag: FDA

Food for Thought: Weekly Wrap-Up

In Frankfurter Allgemeine Zeitung (FAZ), Manfred Lindinger reports on progress in designing intelligent materials. Physicists of Technical University Hamburg-Harburg succeeded in designing gold- and platinum-based materials that can be switched between hard and brittle or soft and elastic, just by applying different voltages. The trick is done by etching pores and channels into the material which subsequently are filled with perchloric acid.

Martina Lenzen-Schulte, also in FAZ, deals with the surprising finding that a screening test for ovarian cancer increases the number cases detected but at the same time does not improve survival. The test based on the CA-125 tumor marker was investigated in the PLCO longitudinal analysis comprising more than 75,000 women aged between 55 and 74 years, who were diagnosed as cancer-free at the beginning of the study. Half of them was tested once a year with the CA-125 test. While more women were diagnosed with ovarian cancer in the CA-125 test group, the outcome did not improve – in part, because the test did not detect the cancer early enough. Moreover, it resulted in a high number of false positives, and these patients were put at unnecessary risk of bleeding, infections, colon injuries and blood loss due to attempts to confirm the diagnosis via biopsies.

In Forbes, Matthew Herper features an interview with David Urdal, the now retiring CSO of Dendreon, who pioneered Provenge, the prostate cancer vaccine approved by the FDA last year as the first anti-cancer vaccine ever. Urdal in detail explains why the company did not specify overall survival as primary endpoint but choose to follow every patient for three years instead. While the FDA first ok’ed the approach and the FDA advisory committee recommended approval in 2007, the FDA did not approve it: in the committee, cell therapists were in favor of Provenge while the oncologists had doubts. The drug was approved only after another study, the famous IMPACT study, had been finished. Urdal maintains that this turned out to be very positive for Provenge: the study revealed new insights about progression in asymptomatic patients and demonstrated that the method to measure disease progression just by counting the time to the next progression event was inadequate. Urdal states that the FDA may have been right to reject Provenge in the first place: “I think if you follow the sentiments within the clinical community I think there was a sense of, okay, if it’s approved I’d probably prescribe it, but geez, it’s a small study, overall survival wasn’t the primary endpoint, there wasn’t a sense of enthusiasm for it, and I think in the end of course the IMPACT study results came back and this completely vindicated the results from the earlier trials.”

William Pentland, also in Forbes, introduces a new battery architecture invented by the Massachusetts Institute of Technology MIT. The semi-solid flow cell basically runs on “sludge”, combining the structure of so-called flow batteries, where the electrolytes are replaced from outside once they are consumed with the favorable energy potential of lithium-ion batteries. Pentland says the new design may have the potential of a game-changer, in particular in combination with electric cars and smart grids.

Todd Woody, also in Forbes, describes buildings that clean up after itself via panels coated with titanium dioxide particles that serve as photocatalysts. Once illuminated by the sun, the particles start destroying dirt on the panel’s surface and, as a side effect, can also clear the surrounding air from nitrogen oxide. The company selling the panels claims they can cut a building’s maintenance costs by a third to half.

The Economist this week makes a case for using personalized medicine approaches in clinical trials earlier. In most cases, the Economist writes, oncologists “base their treatment on where in the body a tumour has sprung up, rather than on which molecular aberrations have caused it”, adding that the same is true for recruiting volunteers for clinical trials, in particular Phase I.

Drawing conclusions from this year’s ASCO (American Society of Clinical Oncology) meeting, the Economist argues it may be much better to match the genetic profiles of patients to the drug being tested, rather than looking for the organs affected. The magazine introduces a study  by Apostolia-Maria Tsimberidou of the University of Texas’s MD Anderson Cancer Centre, in which the author selected volunteers with late-stage cancer across various organs whose tumors were caused by a single, known mutation. 175 volunteers were administered a targeted therapy in a low-dose, Phase I setting while 116 received traditional therapy. In the targeted therapy group, 29% responded, while in the untargeted therapy group there were only 5% responders.

Mark Brown in Wired reports on Harvard University researchers who created the first living laser, a human embryonic kidney cell that was genetically engineered to produce a visible laser beam. The cell producing green fluorescent protein was put between two mirrors and when the team ran pulses of blue light through the cell, it began to emit green light. When bouncing between the mirrors, certain wavelengths were preferentially amplified until a visible laser beam was created for a few nanoseconds. The cell was left unharmed. At present, researchers foresee applications in cell biology research.

Last not least, Herbert Renz-Polster in Der Spiegel this week answers crucial questions on why  kids like jelly babies buth not salad and Brussels sprouts and how they can be made to eat healthy. The answer: it’s the evolution stupid! It is more advisable to eat fat in order to survive the next famine, to eat hastily (who knows when the next rival appears) and it is also wise to avoid eating the unknown (maybe it’s poison). The simple advice: be patient, keep offering the healthy stuff and play while having a meal. That way, kids even learn to like seal fat, whale blubber and roasted locusts.

Food for Thought: Moving Into the Clinic Without Animal Toxicity Tests

This month, MedNous provides an in-depth case study on an immune therapy developed by Immunocore Ltd. that won approval from the British and US regulators MHRA and FDA to start clinical trials on the basis of in-vitro safety studies only – without conducting any toxicity tests in animals.

The product in question, IMCgp100, is a monoclonal T cell receptor fused to an anti-CD3 single chain antibody fragment. The molecule is tricky in that both binding sites bind to human proteins and cells only. As a result, animal studies would have been without any predictive value. The company therefore had to design a reliable preclinical test for predicting the behavior of the drug in humans.

This has been a particular challenge as regulators still were digesting the shock from the TeGenero disaster in 2006, when six healthy volunteers almost died from cytokine storm in a Phase I clinical study of an immune therapy. Back then, the drug had been tested in animals and the volunteers received only a fraction of the dose that had been safely administered to monkeys.

After intense consultations with the regulators, Immunocore conducted a battery of tests on human cells to find out about potential cytokine release, cross-reactivity, etc. The company, too, tested whether hormones were able to shut done activity of the drug in case something would go wrong during the trials.

Trials are on the way already at three UK and two US sites in patients with metastatic melanoma and Immunocore hopes to have preliminary data, including some efficacy results, by 2012.

Food for Thought: In Search of Faster Cures

Last month, The Wharton School of the University of Pennsilvania dedicated a special edition of their prestigious Knowledge@Wharton newsletter to the biopharmaceutical industry. Most importantly, the authors dealt with the pressing question how the industry may continue to develop innovative drugs – and get them approved faster.

Summarizing the current challenges, the report states that “no one doubts that the drug industry’s traditional model for developing new cures is badly broken. Fewer exciting new medicines are reaching patients these days, even as spending on research and development has risen and blockbuster drugs that have long been the backbone of pharmaceutical profits have lost their patent protection. A widening gap divides the discovery of promising new laboratory compounds from the ability to turn them into innovative therapies. A similar gap separates recent scientific gains in understanding genes from the creation of new drugs that use this knowledge to fight disease.”

The report tackles key elements of the ongoing transformation of the biopharmaceutical industry, ranging from novel drug development approaches such as personalized medicine, open-source research, pricing policies, and the latest efforts at the U.S. Food and Drug Administration (FDA) to speed up regulatory processes. One of the most conclusive observations is that partnering and strategic alliances are becoming more important than ever to meet the requirements of the changing pharma industry. However, despite identifying the crucial pieces of the puzzle, it remains to be seen how both established and new biopharmaceutical companies can cope with the challenges of a transforming industry.

Food for Thought: Weekly Wrap-Up

Matthew Herper of Forbes this week takes up the issue whether a DNA sequencer can get FDA approval and quotes Jay Flatley, president and CEO of Illumina as saying the company is in talks with FDA to get regulatory clearance to use its technology for medical diagnostics. He also writes about the late Adriana Jenkins, who worked for Celgene and Third Rock Ventures, among others, and died of breast cancer earlier this month. Having been treated as one of the first patients with one of the first personalized drugs, Herceptin, which gave her a decade of life, she calls for a new law that would give drug companies extended monopolies for developing personalized medicines. Her  own last article explaining her plea for supporting personalized medicine by a legislation similar to the Orphan Drug Act  is featured in Forbes, too.

Also in Forbes, Robert Langreth explains  why Novo Nordisk decided to abandon development of diabetes pills and to ramp up insulin production instead – a move highly successful so far.

Dealing with green energy, the Economist reports on the latest efforts to develop artificial leaves for the synthesis of carbohydrate fuels directly from sunlight, carbon dioxide and water. The article features efforts by the Joint Centre for Artificial Photosynthesis (JCAP) in California, Massachusetts-based Sun Catalyx and a group at Massey University in New Zealand lead by Wayne Campbell.
For those of us who already are short-sighted and need reading glasses on top, the New York Times has good news about a new gadget that already hit the US market. Anne Eisenberg reports that with the new device the days of bifocal spectacles may be over soon. The new emPower electronic spectacles have liquid crystals inserted at the bottom of the lens which change refraction by simply touching the frame. As a result, reading power can be easily switched on and off.

Hannah Waters in The Scientist features a new pathway that may be used to develop novel antibiotics, e.g. to combat Staphylococcus infections.  The trick is done by blocking RNA degradation via a small molecule inhibiting the enzyme RNAse P found in gram-positive bacteria. This leads to accumulation of RNA transcripts and their encoded proteins so that the bugs die from chaos.

In Frankfurter Allgemeine Zeitung (FAZ), Jörg Altwegg reports about a baby that opened up a fierce ethical debate in France. The boy was conceived after preimplantation diagnosis made clear that he not only did not carry beta thalassemia but that he also was suited as a blood donor for his older sister suffering from the disease. Another ethical debate around human genetics is taken up by  Volker Stollorz in a Frankfurter Allgemeine Sonntagszeitung (FAS) article not yet online. In the US, researchers have developed a universal gene test able to uncover the genes for hundreds of severe, rare genetic diseases. The test is going to be used for family planning, and couples at risk of conceiving a child with one of those conditions can opt to perform preimplantation diagnosis. However, while some human geneticists warn that the results might overstrain the expertise of human genetic councelors, others already are crazy about using such tests to eliminate all recessive alleles for genetic diseases from the human gene pool.

Finally, Alison McCook in The Scientist claims researchers are punks, because just like in punk music, as they are typified “by a passionate adherence to individualism, creativity and freedom of expression with no regard to established opinions.” To get a taste, she recommends listening to Minor Threat and Nomeansno for a start.

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