Nature Outlook: Leukaemia

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The leukaemia Outlook is out!

I spent much of April and May working on this special magazine supplement on leukemia for Nature. I came up with the article list, commissioned and edited the articles, worked with the art department on the photos, graphics and cover, and oversaw the production. And I wrote the editorial introducing the contents (below.) You can see the supplement on Nature’s website here.

Of all of the cancers that can wage war on the body, leukaemia — the general term for cancers of the blood — has a reputation for being among the least malevolent.

Most solid cancers are riddled with dozens of mutations, making it impossible to know which mutation set a cell on the wrong path, or which one to target. Leukaemia seems simpler: one type of the disease, chronic myeloid leukaemia (CML), can be traced to a single gene fusion (page S4). Scientists were able to develop a drug, imatinib, that exploits the errant gene, increasing the five-year survival for CML to more than 95%. Most children with acute lymphoblastic leukaemia (ALL) also survive

As we show in this Outlook, however, these headline statistics belie the reality for many patients.

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The FDA tackles tainted drugs from China

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(This story was #3 in Discover Magazine’s top 100 stories of 2008.)

Following a series of high-profile scandals concerning tainted food and drugs imported from China, the U.S. Food and Drug Administration (FDA) announced in March that it would establish a drug-monitoring office in that country.

The most alarming report involved contaminated batches of the blood thinner heparin, which caused at least three deaths and is under suspicion in dozens of others. In February FDA officials admitted that they had never inspected Changzhou SPL, the manufacturing plant in Changzhou, China, to which they traced the contaminated heparin. When the FDA eventually inspected the Changzhou SPL plant (in February), it found a host of quality-control and hygiene problems.

Many drugs sold in the American marketplace are now imported, transforming what was once largely a domestic agency to one that must police products from more than 200 countries, notes Murray M. Lumpkin, FDA deputy commissioner for international and special programs. “The reality of globalization has hit the products for which we’re responsible very, very significantly,” he says. The pharmaceutical production process is also vastly more complex than it used to be. Individual ingredients are made in one place, put together in another, and bottled and labeled in still other sites.

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Rx for the FDA

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(This article was #5 in Discover Magazine’s top 100 stories of 2007.)

For the Food and Drug Administration, the agency charged with ensuring drug safety, 2007 brought a slew of charges undermining its credibility. The most widely reported involved a study by Cleveland Clinic cardiologist Steven Nissen showing that the diabetes drug Avandia, FDA-approved in 1999, raised the risk of heart attack by 30 to 40 percent. The agency was also called to testify before Congress about its inaction regarding side effects of the antibiotic Ketek and a widely used class of anemia drugs. In addition, a study published in the Archives of Internal Medicine in September found that reports of serious side effects and deaths caused by FDA-approved medicines nearly tripled between 1998 and 2005, to about 90,000.

The accumulation of evidence apparently forced a reckoning in Congress and the White House. On September 27, President Bush signed into law an amendment giving the agency unprecedented new powers to conduct and demand safety studies on approved drugs, police drug advertisements, and require companies to register data from their clinical trials in a publicly available database. The new law also boosts the agency’s budget, an increase approved in time to avert the layoffs of some 2,000 FDA employees, including many researchers.

“This has been a tough year,” acknowledges Janet Woodcock, deputy commissioner of the FDA and acting director of the agency’s Center for Drug Evaluation and Research. “[But] I do think this is an inflection point about the communication on drug safety. We have the opportunity to set up new systems.”

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Held to ransom

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(This Opinion column ran on Nature’s news site on March 26, 2007. You can download a pdf of the original post.)

A pharma giant’s decision to withhold new drugs from Thailand will only hurt patients, says Apoorva Mandavilli.

Is there ever a good enough reason to deny life-saving medicines to an entire country’s citizens? I say no. But it seems pharmaceutical giant Abbott begs to differ.

The Chicago-based company decided on 14 March not to introduce in Thailand any of its seven new drugs — including an antibiotic, an important AIDS drug called Kaletra and medicines to treat blood clots, kidney disease and high blood pressure. Without this crucial registration, the drugs cannot be imported to or sold in that country.

It seems to me that Abbott is, in effect, holding millions of Thais’ lives hostage to force their government to respect its patents. This is good business?

The price of drugs varies from place to place.

What’s shocking to me is that the company is making no bones about the fact that its decision is retaliation against Thailand’s decision in January to issue ‘compulsary licenses’ allowing some locals to import or make cheap copies of Abbott’s new version of Kaletra. “This matter is about intellectual property and the integrity of the patent system,” Abbott spokeswoman Melissa Brotz said in a statement.

Lofty words, but I’m reminded more of a schoolyard fight.

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Petition aims to maintain cheap drugs

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(This article appeared on Nature’s news site on January 15, 2007.)

Court case in India threatens to derail generic medicines.

Free for all? Patent laws can make or break generic drug production.

The international humanitarian group Doctors Without Borders (Médecins Sans Frontières, or MSF) is ramping up their fight against the Swiss drug giant Novartis, urging the company to drop a lawsuit that could make it much more difficult for Indian companies to produce cheap, generic drugs.

With the case expected to come up for hearing on 29 January, MSF is pumping up efforts to collect signatures on a petition against the suit. Already they have tens of thousands of names, but are aiming to get many more. A win for the pharmaceutical company, they say, would deprive the world’s poorest people of affordable medicines.

Indian companies are known for making low-cost copies of expensive medicines, particularly AIDS drugs. More than half of the antiretroviral drugs used in developing countries, and about 80% of those provided by MSF, are made by Indian companies. “India is the pharmacy for the developing world,” says Ellen ‘t Hoen, director of policy advocacy for MSF’s Campaign for Access to Essential Medicines. “We largely depend on India.”

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Business: Reinventing an industry

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(I reported this article when I was in India in 2006. Typically, I did not manage to get an interview with Kiran Mazumdar-Shaw till my uncle pulled some strings. Nature has less power in India than nepotism. Also, I’m proud of the fact that, along with an article I wrote about a famous Indian advocacy group, I managed to get photos of two Bollywood stars into Nature. You can download a pdf of this article.)

Two years after a radical change that brought India’s patent laws into line with international trading rules, the country’s drug makers are taking a new direction.

Star turn: Actor Shah Rukh Khan (left) helps Biocon’s Kiran Mazumdar-Shaw launch BIOMAb-EGFR.

Kiran Mazumdar-Shaw is India’s uncrowned queen of biotechnology. She started her company, Biocon, in a garage in 1978 with just Rs10,000 (US$225) in working capital and has built it into the country’s largest biotech company, with 1,800 employees and revenues last year of $180 million.

Said to be the richest woman in India, Mazumdar-Shaw was in the spotlight last September when her Bangalore-based company launched the first new drug to be developed, tested and taken through approval by an Indian company. The drug, BIOMAb-EGFR, is a monoclonal antibody for treating head and neck cancers.

This could be the harbinger of a brighter and more innovative future for India’s drug industry, which until recently relied on sup- plying cheap ‘generic’ copies of drugs — many of which were still under patent elsewhere.

That all changed in January 2005, when India brought itself into compliance with the Trade-Related Aspects of Intellectual Property Rights (TRIPS) — international rules that forbid the copying of patented drugs.

The transition has gone smoothly. “Companies are playing by the rules,” says Frederick Abbott, a professor of international law at Florida State University who knows the Indian drug industry well.

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Premature medication

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(This Opinion column ran on Nature’s news site on December 22, 2006. You can see the original post here.)

Handing out experimental drugs to desperate patients is not a good idea, says Apoorva Mandavilli.

At first glance it seems only kind and right to let people with serious illnesses take whatever medicines they want. Some have campaigned so hard for this that the US Food and Drug Administration agreed on 11 December to let patients buy experimental drugs direct from the manufacturer when there are no other options available.

But this could have some terrible consequences.

Yes, the humanitarian argument for giving access is compelling. And yes, on an individual basis, it seems cruel to deny a medicine to someone who is suffering. But if the drug hasn’t been properly tested, how do we know it won’t aggravate the illness or, worse still, prove fatal to the people who take it? It may even actively discourage companies from investing in proper trials for those drugs where the only customers are desperate patients.

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Your first dose…

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(This is the post I wrote launching Spoonful of Medicine, Nature Medicine’s blog. You can see the original post here.)

Hello everyone!

Welcome to ‘Spoonful of medicine’, where we hope to enlighten, entertain and occasionally exasperate you with our comments on biomedical research and public health.

We hope you’ll be active participants as well, letting us know when we’ve made sense and, of course, when you think we’re stark, raving mad. We hope the proportion is at least slightly more of the former.

Initially, at least, most entries will be posted either by me, Apoorva Mandavilli, or by my colleague, Charlotte Schubert. I am the news editor and am responsible for pretty much everything you read in our news section. You can read more about me here.

Charlotte edits the News & Views section, which involves much editing of copy written by scientists. She’ll say hello soon… you can read more about her here.

Let the games begin…

AIDS care ignores children

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(This article was published on Nature’s news site on 13 July, 2004. I reported this from the XV International AIDS Conference in Bangkok.)

Companies fail to design drugs for kids.

Around 700,000 children were infected with HIV in
2003.

Bangkok – The global fight against AIDS is not addressing children, the very group that is hit hardest by the pandemic, says the medical charity Médecins Sans Frontières (MSF).

In recent years, there has been considerable progress in developing diagnostic tests and anti-AIDS drugs for adults. But doctors lack the simple tools needed to diagnose and treat children infected with the virus.

“Children are a discriminated minority, they are a marginalized community,” David Wilson, medical coordinator of MSF in Thailand told the XV International AIDS Conference in Bangkok.

In 2003, an estimated 700,000 children under the age of 15 were newly infected with HIV. Most of these live in sub-Saharan Africa.

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Troubled times force old pharma to learn new tricks

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(This article appeared in the April 2003 issue of Nature Medicine. You can download a pdf of this article.)

A combination of the floundering economy, a stringent regulatory environment and the dwindling number of drugs in the pharmaceutical pipeline are forcing translational researchers to rethink the way they structure pharma-academic partnerships, heard attendees at the Days of Molecular Medicine conference in March.

“Pharma is in the middle of a major paradigm shift,” said Jeff Leiden, chief scientific officer at Abbott Laboratories. After the golden age of drug development in the 1980s and 1990s, pharmaceutical companies expected their good fortune to continue. Rapid developments in biomedical research only strengthened that expectation, Leiden said. But, “things have certainly changed in the last three years.”

The number of new drug approvals has steadily decreased in the last few years. Researchers also filed fewer applications for patents and inventions in 2002 than in 2001. At the same time, pharmaceutical companies face the daunting costs of bringing a drug to market, pricing pressures and stringent requirements from regulatory agencies; the average size of a clinical trial has nearly tripled in the last 20 years.

Leiden says the existing model, which is a series of hand-offs from academia to biotech companies to large pharma, will soon be obsolete. Instead, he says, his company is actively recruiting both ‘scientist-physicians’—traditional M.D/Ph.Ds who can perform research—and ‘physician-scientists,’ who understand clinical trials and the regulatory hurdles in translational research. Companies like Abbott are also negotiating with universities to train students in both scientific and management principles. “I think you’re going to see a lot of those kinds of programs,” Leiden said.

Some universities are al ready one step ahead. The  University of California in  San Diego—which organized  the conference along with  the Salk Institute and Nature Medicine—is developing a new inter-institutional pro gram called the College of Life Sciences (COILS). COILS  is designed to bridge the  chasms in translational re search and will include the  university’s Institute for Molecular Medicine as the  preclinical arm, the Clinical Investigation Institute for  early-phase clinical trials and  the Academy of Clinician  Scholars to deliver therapies. The university will also offer joint training in science, public health and business.

In the UK, the Medical Research Council (MRC) has in the past two years reorganized its approach to translational research and has begun novel partnerships. For instance, it transferred several MRC employees to a new company, established with Amersham, that provides imaging facilities to the pharmaceutical industry.

The MRC’s new policies reward all staff involved in generating a new patent, a “real important part to encourage young people,” according to MRC chief executive George Radda. The MRC also owns all intellectual property that emerges from research done by its employees at academic institutions, allowing industry to negotiate licenses with a single organization, Radda said.

Researchers who form links with private companies need to be vigilant about potential conflicts-of-interest. Speakers bemoaned the lack of infrastructure to support the training of savvy translational researchers who can navigate such murky waters. M.D./Ph.Ds who exit the university system are better trained in basic research and are pressured to stay in those areas rather than venture into translational research, suggested students who attended the meeting.

Critical to training new physician-scientists is the role of mentors who can help young researchers find their footing. Lloyd “Holly” Smith, associate dean of the University of California in San Francisco, is one such “mentor of mentors,” and was awarded the Mentorship Award at the meeting. Attendees also honored Brian Druker and Charles Sawyers, for their work with the tyrosine kinase inhibitor Gleevec, with the Translational Medicine Award and philanthropist Evelyn Lauder, for her role in raising breast cancer awareness, with the Service Award.