Monthly Archives: November 2011

Pfizer braces for big hit after generic versions of Lipitor hit the market

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Lipitor.jpg

It’s the end of an era for the pharmaceutical industry. Tomorrow, the most popular prescription drug in the world, Lipitor, is due to go off-patent in the US. And no product looks set to equal or surpass the cholesterol-lowering agent’s peak annual sales of $13.7 billion, which it achieved back in 2006.

Lipitor, known generically as atorvastatin, is used by nearly 9 million Americans and has made Pfizer more than $130 billion globally since its 1997 launch. As the drug stands poised at the edge of a proverbial patent cliff, analysts at EvaluatePharma forecast that the loss of the megablockbuster will rob the New York–based drug giant of its top spot in the pharmaceutical league rankings by revenue. As the expiry looms large, patients, pharmacies and the drug industry are all holding their breaths, waiting to see how the introduction of generic atorvastatin will affect them.

For long-term Lipitor users, the patent expiry should be great news. Although Pfizer is expected to take a huge hit with the loss of Lipitor’s exclusivity — about $10 billion a-year by some estimates — consumers should save big. The generic substitute for Lipitor is expected to eventually cost up to 90% less than Pfizer’s drug, and co-payments are expected to drop from an average of $25 per month to $10, saving patients about $180 per year, according to CBS News. To begin with, the Indian drugmaker Ranbaxy Laboratories will hold the exclusive right to manufacture and sell generic atorvastatin in the US, which should help keep the price of the drug relatively high through mid-2012. New Jersey-based Watson Laboratories will simultaneously sell a licensed generic, which will be manufactured by Pfizer. But after six months, other generic version of atorvastatin could flood the market, triggering prices to plummet, and thereby saving consumers and the US health system a whole lot of money.

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Reprogrammed neurons reveal drug lead for incurable childhood disease

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Dolmetsch.jpgUsing the power of reprogrammed stem cells, researchers in California have found a potential new drug lead for a devastating childhood disease that currently lacks good treatment options.

“[The] work is very inspiring,” says Alysson Muotri, a neurogeneticist at the University of California-San Diego who was not involved in the study. “It is a beautiful and elegant manuscript that carefully describes several defects associated with Timothy syndrome brain cells and offers therapeutical opportunities for these families.”

Timothy syndrome is a rare genetic disease marked by mutations in a gene encoding a calcium channel subunit. Children with this genetic defect often develop physical malformations in their hearts and fingers as well as severe neurological problems resembling autism. Doctors typically administer drugs to improve the irregular heart rhythms associated with Timothy syndrome, but there are no therapies available to reverse the developmental irregularities triggered by the disease. So, a team led by Ricardo Dolmetsch at the Stanford University School of Medicine turned to cellular reprogramming to find new drug leads.

The researchers harvested skin cells from a handful of kids with Timothy syndrome and turned them into induced pluripotent stem (iPS) cells. They then coaxed the cells to form neurons (pictured here), and tested a number of known calcium blocking agents for their therapeutic activity. Reporting today in Nature Medicine, they showed that neurons derived from people with Timothy syndrome expressed certain neurotransmitters abnormally, but this trait could be corrected by roscovitine, a drug currently in clinical trials for the treatment of various types of cancer. Roscovitine — which is being developed by Cyclacel Pharmaceuticals of Berkeley Heights, New Jersey under the brand name Seliciclib — also restored cellular signaling in heart muscle cells derived from the same iPS cells, Dolmetsch’s team reported earlier this year in Nature.

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Global Fund halts new funding until 2014

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Crossposted from Nature’s news blog

The Global Fund to Fight AIDS, Tuberculosis and Malaria has cancelled its 11th funding round because of the current economic crisis.

“Substantial budget challenges in some donor countries, compounded by low interest rates have significantly affected the resources available for new grant funding,” the fund said in a statement on 23 November.

It will still provide some funding to existing projects to keep them going over the next couple of years, but will award no new grants before 2014. The fund, a public-private partnership supported by around 150 donor countries, also announced that it would create a new general manager position, taking management responsibility away from executive director Michel Kazatchkine.

Continue reading on Nature’s news blog.

Common autism pathway opens the door for new drug treatments

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main_bg.jpgThe definition of autism has undergone constant evolution — as any architect of the Diagnostic and Statistical Manual of Mental Disorders can attest — and now refers to a broad spectrum of various developmental and social disorders with many distinct genetic causes. This understanding of the disorder obviously complicates the development of therapeutics: if every person with autism is different, identifying drugs to treat everyone seems like a Sisyphean task. But research published today suggests that the disorder’s complexity may not beckon the end of drug development.

Neuroscientist Mark Bear and his colleagues from the Massachusetts Institute of Technology’s Picower Institute for Learning and Memory in Cambridge compared how a protein found in neurons called metabotropic glutamate receptor 5 (mGluR5), which is involved in the translation of other proteins, is regulated in two mouse models for autism: one for fragile X syndrome, the other for tuberous sclerosis. Reporting online in Nature, Bear’s team showed that levels of mGluR5 go up in mice with Fragile X, leading to elevated rates of protein synthesis, but decline in mice with tuberous sclerosis. And despite mGluR5 expression going in opposite directions for the two genetic forms of autism, the researchers managed to fix both defects with experimental compounds that have been demonstrated to either ramp up or dampen mGluR5 signaling. “We’ve identified this single core biochemical pathway of protein synthesis that, if you correct it, you can alleviate those symptoms,” says study author Emily Osterweil, a research associate in Bear’s lab.

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New drug pathways under investigation for ALS

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ALS-nm20111122.jpgA diagnosis of amyotrophic lateral sclerosis (ALS) is considered a life sentence. Most people with the neurodegenerative disease, which attacks the neurons responsible for motor control, only survive two or three years after their diagnosis — and 5,000 such diagnoses are made each year in the US alone. Despite the need, however, there is only a single drug on the market that targets ALS: Rilutek (riluzole), made by France’s Sanofi. But this agent only prolongs life by two or three months on average.

Recent advances provide some hope for future drug pathways that can be targeted to treat the disease. In the latest issue of Archives of Neurology, Teepu Siddique and his colleagues at the Northwestern University Feinberg School of Medicine in Chicago reported finding mutations in the gene that encodes a ubiquitin-binding protein (known as p62 or sequestosome 1) in about 3% of people with either sporadic or inherited forms of the disease. This protein assists the breakdown of other proteins, and its mutation may cause a build-up of dysfunctional proteins in neurons leading to the neurological problems associated with ALS. The research adds to previous findings, including work from the same lab that made a splash in August, implicating the protein degradation pathway in ALS (see our November 2011 news feature, ‘A raw nerve’).

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WHO’s the boss: Chan set to stay at the helm of the global health agency

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margaret-chan-20111120.jpgThe US Republican party has a long list of potential candidates to choose from for the 2012 presidential bid, but the World Health Organization (WHO) has no such leadership race. Today, the WHO, the Geneva-based health arm of the United Nations, announced that the organization had received just a single nomination for its next director-general: the incumbent Margaret Chan.

Chan first got the job after the untimely death of her predecessor, South Korea’s Jong-Wook Lee, in 2006. With her experience tackling epidemics, including Hong Kong’s bird flu and SARS as the special administrative region’s director of health, Chan, who had been working for the WHO since 2003, easily beat out the other 13 nominees for the post.

When Chan took office, she pronounced “improvements in the health of the people of Africa and the health of women” to be the “key indicator of the performance of WHO.” However, her defining role as director-general has probably been her management of the swine flu outbreak in 2009. By declaring a global ‘pandemic’, Chan spurred world leaders into action, and the flu’s spread was halted within months. However, governments spent hundreds of millions of dollars on flu vaccines from Roche and GlaxoSmithKline — many of which went unused. And when word got out that Chan’s emergency swine flu committee included scientists with financial ties to pharmaceutical companies, Chan personally received criticism for allowing pharma interests to have undue influence. The WHO denied the allegations.

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Breast cancer approval revoked for problem-plagued Avastin

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The US Food and Drug Administration announced today that it would be revoking the agency’s approval of Avastin (bevacizumab) for first-line treatment of metastatic breast cancer. The FDA concluded from several studies and a public hearing held in June that the Genentech drug — a monoclonal antibody that inhibits vascular endothelial growth factor — was not safe or effective for women with breast cancer.

“Women risk life-threatening side effects… from taking Avastin and these can be justified only if there was good evidence that use of the drug would benefit the patient,” said FDA commissioner Margaret Hamburg in a media briefing this morning. “After reviewing the available studies, it is clear that there is no proof of a benefit in breast cancer patients.”

The side effects of Avastin include severe bleeding, high blood pressure and heart attacks. Nonetheless, the drug will remain on the market for other types of cancer — including colon, lung, kidney and brain — for which the efficacy outweighs the risks.

The FDA conditionally approved Avastin in 2008 under an accelerated approval process, after positive results from a single study showed almost a half year average increase in progression-free survival in people taking the drug. After two consequent trials by Genentech failed to confirm the original benefits seen, an FDA advisory committee voted 12-1 in July 2010 to revoke Avastin’s approval for this indication. Genentech contested the FDA’s position, requesting a public hearing this summer, but a second, six-member panel unanimously stood by the original decision. Today’s announcement by Hamburg puts a final chapter on this saga.

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Harsher penalties proposed to counter counterfeit drug peddlers

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NM-som-20111118.jpgCongress is, yet again, throwing a fit about counterfeits. Now, US lawmakers from both political parties are proposing a new measure to increase the criminal penalties for the manufacture, sale or trafficking of counterfeit medicines.

Currently, prison times and fines for dealing in counterfeits are the same as any other illegal trade. But “counterfeit medication poses a grave danger to public health that warrants a harsher punishment,” the legislation’s co-sponsor Senator Patrick Leahy, a Democrat from Vermont, wrote in a statement. The Counterfeit Drug Penalty Enhancement Act, introduced yesterday in both houses of Congress, would increase the maximum penalties for first-time offenders to 20 years in prison with a $4 million fine; repeat offenders could be dinged as much as $8 million.

But, if precedent on Capitol Hill means anything, this bill is not set to go far. Tim Fagan’s Law, named after a teenager who was injected with counterfeit medicine after a live transplant, was first proposed in 2003 to increase penalties for dealing in counterfeit drugs. However, the legislation has been sitting pretty in committee for six years now, and is reintroduced every year with no advance.

For more on counterfeits, read our April 2010 news focus on the subject.

Image: Bag of seized counterfeit Viagra (sildenafil) via Wikimedia Commons

Straight talk with… Steve Brown

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nm1111-1332-I1.jpgFor decades, the study of gene function has relied heavily on the creation of ‘knockout’ mice, bioengineered to lack certain genes. But making a rodent without a specific gene is a chore—so much so that doctoral students sometimes dedicate their entire PhD work to generating a single mouse strain. The International Knockout Mouse Consortium (IKMC), launched in 2006, plans to change all that. The consortium, involving scientists from 33 research centers in nine countries, is creating a library of every gene knockout in embryonic stem cell lines, which can be used to produce mouse strains.

In June, the group passed 10,000 embryonic stem cell lines generated in a targeted fashion, and, as they approach their goal of around 21,000 mouse gene knockouts, the project is moving onto its next step: phenotypes. The offshoot collaboration, the International Mouse Phenotyping Consortium (IMPC), plans to document disease-related phenotypes for each generated mouse strain including metabolic, neurological and behavioral data. The effort received support on 29 September, when the US National Institutes of Health (NIH) awarded $110 million to three US centers over five years to phenotype 833 strains each. Hannah Waters spoke with Steve Brown, chairman of the IMPC and director of the UK Medical Research Council’s Mammalian Genetics Unit in Harwell to learn more about the plans for the project.

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Geron abandons stem cell research

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Crossposted from Nature’s news blog

geronA company that pioneered embryonic stem cell research is walking out on the field it helped to create. Geron, based in Menlo Park, California, announced yesterday that it would kill off its stem cell program — and its landmark clinical trial of a treatment for spinal cord injuries — so that it can focus on cancer therapies.

For supporters of the technology, Geron’s exit is a blow. “This is very unfortunate for the field,” says Robert Lanza, chief scientific officer of Advanced Cell Technology, the only other embryonic stem cell company with regulatory approval to conduct clinical trials in the United States. “It is a big deal. It certainly puts a lot of pressure on us to deliver now.”

Geron was the first company to gain approval from US regulators to conduct a clinical trial using human embryonic stem cells. The company has treated four patients with spinal cord injuries since it launched the trial in 2010, and has reported that the treatments appear to be safe though they have not yielded any improvement in spinal cord function. The trial was only designed to test safety, however, and Geron has made it clear from the start that the company did not expect the treatment regimen — including the number of cells injected — to be sufficient to relieve paralysis in the ten patients it ultimately aimed to treat in its first trial.

Continue reading on Nature’s news blog.