FDA sets draft rules for biotech drug copies

By Deena Beasley

Thu Feb 9, 2012 4:46pm EST

(Reuters) - The Food and Drug Administration's long-awaited guidelines for the sale of lower-cost versions of biotechnology drugs leave open the possibility that some products might not need to be tested in humans.

The proposed rules, issued on Thursday, require studies showing that the generic copies are "highly similar" to the originals, but there are several ways that might be proven.

Because of their complexity, generic copies of biotech drugs - first introduced in the 1980s - are known as "biosimilars."

"We're trying to send the signal that it's not one-size-fits-all. It's product-by-product," Rachel Sherman, director of the FDA's office of medical policy, said during a conference call with reporters.

The worldwide market for copies of biotech medicines will grow to $3.7 billion by 2015, from just $243 million in 2010, as more than 30 branded biologics with sales of $51 billion lose patent exclusivity, according to market analysis firm Datamonitor.

The FDA rules would set "an abbreviated pathway" to approval that would consider factors including a product's complexity, formulation and stability, the agency said.

The proposal "reads largely as we expected, although a few points read as slightly more friendly to the generics industry," ISI Group analyst Mark Schoenebaum said in a note to clients.

The FDA said it would decide on the "extent and scope of animal and clinical studies" needed for approval once it has considered other analytical data. The agency said it has yet to receive an application for a biosimilar drug, but nine applications have been filed for clinical trials.

Manufacturers will have the option of asking the FDA to deem their copies "interchangeable" with a brand-name drug, but the `agency said that would require additional clinical studies.

Makers of branded biotech drugs have argued that full-scale human trials need to be conducted before a rival version of an existing biologic drug should be allowed on the market.

Despite such qualms, biotech drug makers including Amgen Inc, Merck & Co and Biogen Idec are working to produce rival versions of biotech drugs made by competitors.

"While the documents provide a roadmap, they are sufficiently vague as to give FDA leeway for case by case assessments of each proposed biosimilar along their respective development paths," said Wells Fargo analyst Brian Abrahams.

The Congressional Budget Office has estimated that the United States could save $25 billion from the use of biosimilars over 10 years.

European regulators have already approved cheaper versions of some biotech drugs.

The FDA said advances in science and manufacturing may facilitate fingerprint-like analysis of therapeutic protein products, which may allow for a more selective approach to any animal or human studies.

Unlike conventional, easy-to-replicate, chemical-based drug compounds, biotech drugs are derived from living organisms, such as proteins, and are often produced using recombinant DNA technologies.

Once a traditional pill loses patent protection, there is a quick regulatory pathway for generic drugmakers to sell much cheaper versions of the branded medicine. Similar U.S. guidelines for biotech drugs have been under negotiation for several years.

Biosimilar drugs are expected to sell at discounts of 25 to 45 percent to branded rivals, compared with generic versions of traditional pills that often sell for one-tenth the price of the branded product.

Under the U.S. healthcare reform law passed in 2010, brand-name biotech drugs - ranging from relatively simple molecules like insulin to complex antibodies used to treat cancer - were granted a 12-year period of market exclusivity, after which generic versions can be sold.

Opposing trade groups - the Biotechnology Industry Organization and the Generic Pharmaceutical Association - said they are reviewing the proposed rules.

The generic drugs group said it was pleased with the FDA's action, which it called "an important step in getting these affordable, lifesaving medicines into the hands of doctors and patients."

The FDA will require that biosimilar manufacturers provide a post-marketing safety monitoring program, which in some cases may include long-term clinical studies.

The agency is accepting public comment on the draft guidance documents for the next 60 days.

(Reporting by Deena Beasley in Los Angeles, Additional reporting by Bill Berkrot in New York and Anna Yukhananov in Washington; Editing by Gerald E. McCormick, John Wallace and Matthew Lewis)

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New mental health manual is "dangerous" say experts

By Kate Kelland, Health and Science Correspondent

LONDON | Thu Feb 9, 2012 2:24pm EST

LONDON (Reuters) - Millions of healthy people - including shy or defiant children, grieving relatives and people with fetishes - may be wrongly labeled mentally ill by a new international diagnostic manual, specialists said on Thursday.

In a damning analysis of an upcoming revision of the influential Diagnostic and Statistical Manual of Mental Disorders (DSM), psychologists, psychiatrists and other experts said new categories of mental illness identified in the book were at best "silly" and at worst "worrying and dangerous."

"Many people who are shy, bereaved, eccentric, or have unconventional romantic lives will suddenly find themselves labeled as mentally ill," said Peter Kinderman, head of Liverpool University's Institute of Psychology at a briefing in London about widespread concerns over the manual.

"It's not humane, it's not scientific, and it won't help decide what help a person needs."

The DSM is published by the American Psychiatric Association (APA) and has symptoms and other criteria for diagnosing mental disorders. It is used internationally and seen as the diagnostic "bible" for mental health medicine.

No one from the APA was immediately available for comment.

More than 11,000 health professionals have already signed a petition (at dsm5-reform.com) calling for the development of the fifth edition of the manual to be halted and re-thought.

Some diagnoses - for conditions like "oppositional defiant disorder" and "apathy syndrome" - risk devaluing the seriousness of mental illness and medical zing behaviors most people would consider normal or just mildly eccentric, the experts said.

At the other end of the spectrum, the new DSM, due out next year, could give medical diagnoses for serial rapists and sex abusers - under labels like "paraphilic coercive disorder" - and may allow offenders to escape prison by providing what could be seen as an excuse for their behavior, they added.

RADICAL, RECKLESS, AND INHUMANE

Simon Wessely of the Institute of Psychiatry at King's College London said a look back at history should make health experts ask themselves: "Do we need all these labels?"

He said the 1840 Census of the United States included just one category for mental disorder, but by 1917 the APA was already recognizing 59. That rose to 128 in 1959, to 227 in 1980, and again to around 350 disorders in the fastest revisions of DSM in 1994 and 2000.

Allen Frances of Duke University and chair of the committee that oversaw the previous DSM revision, said DSM-5 would "radically and recklessly expand the boundaries of psychiatry" and result in the "lexicalization of normality, individual difference, and criminality."

David Pilgrim of Britain's University of Central Lancashire said it was "hard to avoid the conclusion that DSM-5 will help the interests of the drug companies."

"Madness and misery exist but they come in many shapes and sizes," he said. "We risk treating the experience and conduct of people as if they are botanical specimens waiting to be identified and categorized in rigid boxes.

"That would itself be a form of collective madness for all those complicit in the continuing pseudo-scientific exercise."

Nick Craddock of Cardiff University's department of psychological medicine and neurology, who also spoke at the London briefing, cited depression as a key example of where DSM's broad categories were going wrong.

Whereas in previous editions, a person who had recently lost a loved one and was suffering low moods would be seen as experiencing a normal human reaction to bereavement, the new DSM criteria would ignore the death, look only at the symptoms, and class the person as having a depressive illness.

Other examples of diagnoses cited by experts as problematic included "gambling disorder," "internet addiction disorder" and "oppositional defiant disorder" - a condition in which a child "actively refuses to comply with majority's requests" and "performs deliberate actions to annoy others."

"That basically means children who say 'no' to their parents more than a certain number of times," Kinderman said. "On that criteria, many of us would have to say our children are mentally ill."

(Editing by Andrew Heavens)

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The trials of creating a hepatitis C vaccine

Oxford Clinical Trials

New research from the University of Oxford is using cutting-edge science to solve the problems associated with creating a hepatitis C vaccine

Hepatitis C is a problematic disease, for patient and clinician alike. In the UK, up to 500,000 people may be infected with the virus, and globally the World Health Organization believes the figure could be as high as 170 million people. Particularly troubling is the fact that the virus can go unnoticed for years, but during that time is capable of causing considerable liver damage.

But weight of numbers isn’t the only difficulty. In fact, perhaps the biggest barrier to creating an effective hepatitis C vaccine is the fact that the virus changes its appearance, making it hard to find a point to target in order to defeat it. “One of the big issues is the variability of the virus,” explains Dr Ellie Barnes form the Jenner Institute. “In fact, it’s ten times more variable than HIV.”

A team at the Jenner Institute led by Dr Barnes have, however, been working to create a vaccine that manages to target the small part of the virus that never changes. To do that, they captured roughly two thirds of the hepatitis C genome, and then attached it to rare adenoviruses -- essentially, strains of the common cold. By using rare adenoviruses, one of which was derived from chimpanzees, itself a world-first, the team could be sure that patients had never been exposed to them before -- a fundamental requirement for the vaccine to work.

As the team report in Science Translational Medicine, they have so far conducted a phase 1 trial in 41 patients, and the results are promising. In fact, the vaccine has been shown to produce a very strong immune response, which lasted a year, and had no major side-effects.

Prof Paul Klenerman, also of the Jenner Institute said: "The immune responses we've seen are exciting and we are beginning the next stage of trials. While we are hopeful, it could be a long road to any vaccine that protects people against hepatitis C."

The next step is to move the research forward into phase 2 trials, testing whether the vaccine can protect people who are at risk of contracting hepatitis C. In fact, those trials are already under development in the US, funded by the NIHR, and are due to commence in late 2012.

Read more in Science Translational Medicine

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