Monthly Archives: July 2011

FDA committee votes down first-of-a-kind diabetes drugs

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diabetes-testing-strips.jpgThe first of a highly anticipated class of diabetes drugs assessed by the US Food and Drug Administration (FDA) got the thumbs-down from the agency’s Endocrinologic and Metabolic Drugs Advisory Committee yesterday. The FDA panel rejected dapagliflozin, developed by Bristol-Myers Squibb and AstraZeneca, by a 9–6 margin.

Unlike current type 2 diabetes medicines, which modulate insulin activity to affect sugar levels in the bloodstream, dapagliflozin regulates blood sugar independently of insulin by preventing the protein sodium-dependent glucose cotransporter 2 (SGLT2) from reabsorbing glucose into the kidney. Usually, this simple sugar is dumped back into the bloodstream, inducing a symptom known as hyperglycemia. But dapagliflozin and similar drugs in development cause the kidney to excrete the excess glucose into the urine.

These SGLT2 inhibitors excite researchers and doctors because they provide “a new option for patients with diabetes with a totally different mechanism of action,” says Steven Shoelson, head of pathophysiology and molecular pharmacology at the Joslin Diabetes Center in Boston who is not involved in the development of these drugs.

In phase 3 trials, dapagliflozin proved to regulate blood sugar and even caused weight loss in many of study subjects. However, the FDA panel voted down the drug because of safety issues. Notably, patients taking dapagliflozin had higher rates of breast and bladder cancer compared to those in the control arms of the trials.

Looking ahead, other drugmakers developing experimental SGLT2 inhibitors will have to “be very careful to make sure that they do sufficient numbers of people to test [cancer incidence] adequately,” says Shoelson. Johnson & Johnson have a drug called canagliflozin in phase 3 trials, and Boehringer Ingelheim and Lexicon Pharmaceuticals have a related agent in phase 2 testing.

The FDA doesn’t have to follow the recommendations of its advisory panels, but it usually does. A final decision is due 28 October.

Image: Flickr user bodytel, under Creative Commons

Experts hash out guidelines for HIV trials involving men who have sex with men

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ROME — Last week’s encouraging results from two trials showing that prophylactic use of AIDS drugs in HIV-negative people can help prevent infection has underscored the value of studying new preventative treatments, particularly in high-risk groups. And one of the highest risk groups remains men who have sex with men — a term used to include men who might not self-identify as gay.

In the US, for example, men who have sex with men (MSM) represent about 2% of the population, but they accounted for 59% of new HIV diagnoses in 2009. Strikingly, a global review estimated that only 3.3% of HIV prevention spending goes to address the needs of the MSM community in parts of the world where the epidemic is concentrated.

In hopes of facilitating more work in this area, experts from groups such as the Foundation for AIDS Research (amfAR) and the International AIDS Vaccine Initiative held a session at the International AIDS Society meeting here this week to discuss a draft set of guidelines. Although the World Medical Association and UNAIDS have published research principles for biomedical trials in the past, the authors of the newly drafted guidance say it’s the first of its kind to specifically advise on HIV research among individuals who fall into the MSM and LGBT (gay, lesbian, bisexual, transgender) categories.

The draft guidance stresses that consensual same sex practices are illegal in some countries and stigmatized, sometimes by the findings of HIV research itself. “That is a real obstacle to the response,” says Chris Beyrer, director of the Johns Hopkins Center for Public Health & Human Rights in Baltimore, Maryland, an institute involved in drafting the document. He adds that the problem is “really troubling” in former Soviet states such as Uzbekistan and Ukraine where the epidemic is intensifying.

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A new eye on immune responses to tissue transplants

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Immune cells travel all over the body, prowling for foreign agents to attack — including transplanted organs. The specifics of transplant rejection remain a topic of intense scientific scrutiny, but it’s been difficult for researchers to observe how and when immune cells gather at the organ during rejection, and how they act once they arrive.

Now, Alejandro Caicedo and his colleagues at the University of Miami Miller School of Medicine describe a new technique that provides a fresh perspective on the immune reaction triggered by organ transplants. In a study published online today in the Proceedings of the National Academy of the Sciences, Caicedo’s team transplanted mouse pancreatic cells into the eyes of living mice, and then waited for organ rejection. Using various cell dyes, they took advantage of the eye’s semi-translucence to watch the immune response happen in real time.

The eye “is a window into the body,” says Caicedo. “It’s easy to access and very easy to see.”

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Scaled-up study of soldiers points to doubled risk of dementia from head injury

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PARIS — A massive review of the medical records of nearly 300,000 US veterans lends weight to the notion that traumatic brain injury might contribute to the risk of cognitive impairment later in life. Neurologist Kristine Yaffe of the University of California–San Francisco and her colleagues reviewed seven years’ worth of data from the files of the former military troops, and found that these types of head injuries were linked to a doubled risk of dementia.

Yaffe, who presented the findings here today at the Alzheimer’s Association International Conference, says that it’s the largest analysis of its kind to date. All of the 281,540 veterans included in the analysis were aged 55 years or older and free of dementia at check-up visits before 2001. However, during seven years of follow up, 2% of the older veterans had a diagnosis of traumatic brain injury (TBI). Of those with TBI, 15.3% developed dementia, as opposed to 6.8% of those who were free of this type of head injury. After adjusting for other possible contributing factors, such as post-traumatic stress disorder — which previous research has hinted might contribute to impaired cognitive function — the scientists calculated that TBI is linked to a 2.3-fold increased risk of dementia.

Based on the limitations of the medical records, Yaffe and her colleagues were unable to determine the severity and extent of the head injuries among the veterans who had a TBI diagnosis. “We couldn’t delve down and say whether it was repetitive or not,” she explains. She adds that while her team was able determine the type of TBI the veterans sustained, ranging from skull fractures to concussions, the dementia risk did not seem to vary much between the kinds of head injury.

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New Hollywood thriller follows contagious plotline

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Biomedical scientists are slated to hit the silver screen again. In September, Warner Bros will release Contagion, an action-thriller that “follows the rapid progress of a lethal airborne virus that kills within days.” According to the official website, the film features a number of US government scientists and doctors who try to contain the outbreak, and, unsurprisingly, how “ordinary people struggle to survive in a society coming apart.”

WB released the film’s trailer yesterday, which you can watch here.

Beside the star-studded cast — which includes Gwyneth Paltrow, Matt Damon, Laurence Fishburne, Kate Winslet and Jude Law — the preview features many hallmarks of epidemic films, including a chained monkey in a cage, a mention of the virus mutating, and even a conspiracy theory — “the truth is being kept from the world,” croons a voiceover.

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Medical experts grapple with an eight-legged problem

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Snake bite treatments have been all the rage of late here at Nature Medicine. This month, we have a podcast interview with the author of a recent paper who found that applying an off-the-shelf ointment can slow the spread of snake venom. Last summer, we reported how drug companies aren’t developing new antivenom therapies despite the medical need. And dipping into the archive, five years ago we published a commentary on the role that the immune system’s mast cells play in inactivating snake toxins.

But snakes aren’t the only vermin with a venom-filled bite. Each year hundreds of thousands of people around the world are bitten by venomous spiders. Some of these, such as the redback spider of Australia, cause neurotoxic effects, leading to cramps, nausea, paralysis and even death. Others, including North America’s brown recluse spider (pictured at right), have cytotoxic venom that kills cells and tissue leading to nasty, ulcerated wounds.

As such, one might think that spider antivenoms, which have been on the market for over half a century, could go a long way to treating the effects of these eight-legged onslaughts. But in practice, antivenoms are largely ineffective because spider bite victims often don’t know for many hours that they’ve been nipped. This means that bite victims generally fail to seek medical help fast enough for these treatments to make a difference, two spider bite experts argue in a report out this week in The Lancet.

“Antivenom is never going to be of any practical value because you can’t administer in a way that’s going to work,” says study coauthor Geoff Isbister, a clinical toxicologist at the University of Newcastle in Australia. “If this was a drug developed in the last 20 years it would never have got through” regulatory scrutiny, he adds.

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Pfizer breaks from merger mentality as others chase leads

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By Janelle Weaver

It was less than two years ago that the pharmaceutical giant Pfizer made headlines when it acquired the drugmaker Wyeth for a cool $68 billion. But these days Pfizer is generating a buzz for mulling over a different way to bump up its bottom line: shedding some of its nonpharmaceutical divisions. The potential plan has not won over all industry analysts, some of whom say that scooping up smaller companies with strong drug pipelines—particularly those in developing markets—still offers the best path to profits.

The takeover of Genzyme by Sanofi this past spring was only the latest in a string of companies combining, going back to the Merck-Schering-Plough and Roche-Genentech fusions in 2009. These strategic rearrangements of industry titans have largely been a response to looming patent losses. Over the next two years, patents will expire on more than a dozen blockbuster drugs with combined annual sales of about $50 billion, according to the research organization EvaluatePharma in London.

Notably, New York–based Pfizer will bear the brunt of the so-called ‘patent cliff’ this year, when it loses its exclusivity rights for the cholesterol fighter Lipitor (atorvastatin)—the best-selling medication in the US—and the antacid Protonix (pantoprazole). More than two thirds of the company’s portfolio—worth more than $35 billion—will be at risk in the next three years owing to patent expirations, according to EvaluatePharma.

The company could increase its profits by becoming a leaner machine and focusing on neuroscience, vaccines and other core therapeutic areas with the greatest growth potential according to David Amsellem, a New York–based analyst with Piper Jaffray. He cites Sanofi’s decision to sell its dermatology business to focus on high-growth areas as an example of this type of strategy. “You’re going to see these kinds of transactions become increasingly common,” says Amsellem.

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An audience with the head of the US-Russian Scientific Forum

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By Gary Peach

nm0711-764-I1.jpgRussian medicine is—at long last—undergoing a renaissance. The country’s rocky economic ride following the collapse of the Soviet Union disrupted its research rubric and impoverished its healthcare system. Now, however, the nation’s leadership is spearheading various initiatives to reverse the situation. One of them, the US-Russian Scientific Forum, established two years ago by a bilateral presidential commission, hopes to bring improvements by facilitating public-private research in biomedicine and innovative drugs. The Forum, which on the Russian side is represented by the country’s Ministry of Health and Social Development and the Russian Academy of Sciences, among others, held its inaugural planning meeting in late April in Moscow. Valery Danilenko, who is helping to spearhead the effort and also leads the biotechnology division at the Vavilov Institute of General Genetics in Moscow, told Nature Medicine about the meeting and Russia’s hopes for the Forum. The interview was conducted in Russian and translated by the interviewer, Gary Peach.

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After GAVI pledges surpass goals, focus shifts to keeping promises

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By Georgina Kenyon

LONDON — In a move that surpassed expectations given the tough economic times, donors committed $4.3 billion to the GAVI Alliance at a 13 June pledging conference—exceeding the target of $3.7 billion. The funds secure the next five-year chapter of the Geneva-based public-private partnership aimed at stamping out preventable illness in the world’s poorest countries—in particular, two of the biggest child killers, pneumonia and diarrhea.

“Now poor kids will get the vaccines that rich kids get,” Bill Gates, whose Bill & Melinda Gates Foundation is slated to give GAVI more than $1 billion, said at the meeting here.

Some of the largest government pledges came from the UK ($1.3 billion), Norway ($819 million) and France ($511 million). Notably, the current framework is such that approximately 85% of GAVI support is in-kind donations of materials such as vaccines.

Looking ahead, the organization is pushing to shape vaccine markets and drive down prices by involving more developing-world–based pharmaceutical companies in vaccine research and manufacturing. But there are some voices that are doubtful of GAVI pushing enough to reduce the costs of vaccines.

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Companies vie for a cut of the gene-editing market

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By Daniel Grushkin

Researchers hoping to write the next chapter of biomedicine know that their progress will hinge largely on their ability to edit genes — cutting out unwanted DNA and manipulating the sequences they want to keep. Acolytes of gene-editing technology have recently been encouraged by early data about Sangamo BioSciences’ new zinc finger nuclease–based therapies. In March, the California biotech reported preliminary phase 1 trial results showing that its HIV treatment, which uses editing to turn off the gene for the receptor on the cell membrane that the virus exploits, was safe and effective at improving people’s T cell counts. Two months later, Sangamo scientists presented additional evidence at the American Society of Gene & Cell Therapy meeting in Seattle demonstrating in mouse and cell models the technology’s promise in a number of other diseases, including hemophilia, so-called ‘bubble boy disease’ and a form of acquired blindness.

Sangamo’s success has fed a growing enthusiasm for genome engineering technologies. And now, a handful of biotechs with competing technologies and business models are vying to be the go-to company for gene-editing applications. But not all technologies are created equal, and there’s debate within the research community about which technique is best for which purpose. “It’s a bit like ‘which one will win out — PCs or Macs?’,” says Bert Vogelstein, a cancer researcher at the Johns Hopkins University School of Medicine in Baltimore. “The one people will choose is the one that’s available, easiest, cheapest and the one they have experience with.”

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