News

Food for Thought: It’s becoming a habit – IQWiG takes approval studies apart

Germany’s Institute for Quality and Efficiency in Health Care (IQWiG) this year put out several negative assessments of newly introduced drugs, stating the data did not prove “additional benefit” over existing treatments. In all cases, IQWiG came to the conclusion after deviating from the study design the companies had discussed with the regulators. Instead, IQWiG’s experts divided the patient population into subgroups, saying those subgroups needed different comparator treatments. As a result, these data were either not available or the subgroups were too small to demonstrate statistical significance.

One example is Pfizer’s Xiapex injectable collagenase, approved in early 2011 to treat Dupuytren’s contracture. IQWiG stated that Xiapex does not provide an additional benefit to patients because “it was not possible to derive such additional benefit from the dossier and because the manufacturer did not provide additional or suitable data” to substantiate the claim.

While the manufacturer had compared the Xiapex injection to a surgical treatment, partial fasciectomy (PF), IQWiG for its assessment established six subgroups of patients according to the severity of the disease and chose three different treatment options as comparator: no therapy, percutaneous needle fasciectomy (PNF) and partial fasciectomy (PF). As a result, IQWiG was able to state that Pfizer did not provide evaluable data because the company’s selected comparators differed from IQWiG’s comparators for all but one patient subgroup.

In the case of Eisai’s breast cancer drug Halaven eribulin, IQWiG’s verdict ruled that it could not find evidence for eribulin resulting in a prolonged life expectancy. IQWiG added that Halaven might provide an overall survival benefit for patients for whom taxanes or anthracyclines are no longer an option, but it was unclear whether the benefit was significant. Again, the assessment was made by subdividing the patient group. IQWig defined two subpopulations – one for which an additional anthracycline or taxane treatment was thought to be an option and one for which this was not.

Eisai, in contrast, had compared Halaven to a “Treatment of Physician’s Choice” (TPC) as there are no established national or international treatment guidelines for a standard therapy of women with metastatic or locally advanced breast cancer after failure of two standard chemotherapies including an anthracycline or taxane. This design of Eisai’s EMBRACE was established in discussions with the European Medicine’s Agency (EMA). Being a European study, the participating physicians sometimes opted for therapies not approved in Germany – a reason for IQWiG to not include these data in its assessment. As a result, only 69% of the EMBRACE study patients were regarded as suitable for an assessment.

The same approach was taken in the assessment of Novartis’ Gilenya fingolimod, the first oral treatment for Multiple Sclerosis (MS) approved in 2011. IQWiG once again performed separate assessments of the drug in three groups of patients, choosing three different comparators. Following this operation, IQWiG was able to find data only for one of these subgroups in the study, not enough to establish an additional benefit with sufficient statistical significance. However, one of the comparisons chosen by IQWiG – fingolimod against glatiramer acetate in patients with relapsing/remitting MS – would have been impossible as fingolimod is approved as second-line therapy in this indication while there are no studies of glatiramer acetate differentiating between first-line and second-line treatments.

In all cases, manufacturers may respond to the assessment, after which the Federal Joint Committee (G-BA) will review IQWiG’s recommendation before making a final decision.  If G-BA deviates from IQWiG’s negative assessment, the manufacturers have to negotiate the price with the Statutory Health Insurance Funds Association (GKV-Spitzenverband) under the AMNOG pricing scheme. If G-BA agrees with the IQWiG assessment that a drug has no clinical benefit beyond available treatments, the drug will be added to the reference pricing system, which gives the same base price to all comparable drugs in the respective therapeutic group.

Food for Thought: “Forget Alzheimer’s”? – A Book Review

“Forget Alzheimer’s” is the title and the message of a book by German journalist Cornelia Stolze who is claiming to tell the “truth about a disease which isn’t one” (Cornelia Stolze, Vergiss Alzheimer. Die Wahrheit über eine Krankheit, die keine ist, Köln/Cologne 2011: Kiepenheuer & Witsch).

The book is strongly criticizing the handling of dementia, in particular Alzheimer’s disease (AD) in today’s medicine, pointing out the lack of adequate diagnostics and therapies and contrasting this sad reality with the often exaggerated promises of imminent breakthroughs by experts.

Stolze starts by explaining that to date, it is extremely difficult to diagnose Alzheimer’s disease. Most claims about new methods to confirm a diagnosis or, even better, to predict the onset have turned out to be false. She also points out that about 50 diseases and at least 150 medications may cause dementia symptoms. She concludes that most physicians are overextended to differentiate and often too early and too easily put the patient down as having Alzheimer’s, thereby impeding a causal treatment and condemning the patient to unnecessary mental derangement.

Examples are cognitive impairments associated with dehydration and depression, but also a variety of drugs, in particular, if patients take cocktails of drugs prescribed by different specialists who neglected potential interactions and side effects. Complications during surgery or anesthesia, too, can cause dementia symptoms. Stolze summarizes that about 75% of all dementia diagnoses are false.

She also points out that most medications on the market for the treatment of AD are ineffective, do not provide causal therapy and may at best slow down disease progression for a limited period of time.

These chapters are a strength of the book and can be read as a roll call to relatives, patient advocacy groups and the health care system in general to raise awareness about the various forms of dementia and to demand better diagnosis and better drugs.

Stolze then tells the 1970s story of how Alzheimer’s disease was put on the agenda of the then newly founded US National Institute on Aging (NIA). Back then, little was known about Alzheimer’s disease, but using a fancy name describing a threatening disease was way more efficient in raising awareness and money from governments and private sponsors than by talking in general terms about senility or dementia.

Subsequently, Stolze’s story gets astray as she tries to convince the reader that AD has been and still is a mere invention by the medical industry, and that every scientific description of the disease – whether in terms of pathology, biochemistry or cellular and molecular biology – is full of errors, inconsistencies and contradictions.

The author makes no efforts to go into the details to substantiate this claim. As an example, Stolze writes that plaques – long viewed as the hallmarks of AD – can be found in the brains of mentally wide awake elderly as well. She ignores that this fact has puzzled researchers since long and that there is an explanation to it already: plaques in the brain of healthy people do have a different molecular composition than those in people with AD, in which they predominantly consist of a certain, very toxic variant of the A beta peptide. The details have been elucidated by researchers from the German biotech company Probiodrug, with the first publications appearing in the late 1990s. The hypothesis meanwhile has been confirmed independently by various research groups around the world and a first drug addressing the underlying mechanism already has reached clinical stage.

Moreover, Stolze completely ignores that there are inherited forms of AD such as Familial Alzheimer’s disease (FAD) or Early Onset Familial Alzheimer’s disease (EOFAD), uncommon forms of Alzheimer’s disease which usually strike quite early in life. They are inherited in an autosomal dominant fashion and the genes involved have been characterized years ago. Moreover, studies in these inherited forms have revealed further details of the pathophysiological mechanisms involved in AD in general.

Further parts of the book deal with selected German Alzheimer specialists and their connections to industry and politics, raising questions about conflict of interest disclosures. This is an ongoing debate in medicine in general, and Stolze seems to share the widely held beliefs in Germany that a researcher or medical doctor, who files for a patent, already has crossed the line to unethical behavior.

Most regrettable about the book is that it shakes the confidence in medicine of patients, relatives and people involved in the care of dementia patients without providing any valuable guidance what to do and whom to trust if a loved one is showing signs of confusion, disorientation or loss of memory.


Company News: Anergis Appoints Jacques-François Martin as Chairman of the Board of Directors

Anergis, a clinical-stage biopharmaceutical company developing novel allergy vaccines, today announced the appointment of Jacques-François Martin, Chairman and CEO of vaccine company Mymetics, as Chairman of the Board of Directors.

Anergis develops allergy vaccines based on its proprietary technology of “Contiguous Overlapping Peptides” (“COPs”). Anergis’ lead allergy vaccine, called “AllerT”, is in clinical Phase IIb development and is designed to provide ultra-fast and safe desensitization to birch pollen allergy, a widespread condition in developed countries. Anergis’ vaccines are designed to provide long-term protection against allergies with a 2-month treatment.

Jacques-François Martin is Chairman and CEO of Mymetics Corporation. Previously, he was CEO of Chiron Vaccines (now Novartis) from 1991 to 1993 and CEO of Pasteur-Mérieux (now Sanofi-Pasteur) from 1988 to 1991. In addition, he held leadership positions with not‐for‐profit organizations dedicated to the development of vaccines for debilitating and life-threatening diseases in both developed nations and third world countries. Among others, he was the first President and CEO of The Vaccine Fund (Bill and Melinda Gates Foundation) from 2000 to January 2005 and a member of the Board of the International AIDS Vaccine Initiative (IAVI) from November 1997 to June 2003. He started his executive career as Chief Executive Officer of Rhône-Poulenc Pharma in Hamburg, Germany, in 1970. Mr. Martin is a member of the French Academy of Technologies and an officer in the French Order of Merit.

Company News: bubbles & beyond presents product update and outlook at nanotech 2012

bubbles & beyond, a technology company focusing on customized intelligent fluids®, today announced that the company will present its current product portfolio and business strategy for 2012 at the upcoming nanotech 2012 conference in Tokyo, Japan (Feb. 15-17).

Intelligent fluids® are customized phase fluids, which are primarily designed for cleaning, separating and protecting surfaces. They significantly outperform competitive products in terms of efficiency and eco-friendliness. The technology platform is suitable for functional cosmetics, healthcare and industrial cleaning applications (construction, microelectronics, industrial solutions, print rolls, etc.). Products and processes based on intelligent fluids® are free from risky or dangerous substances and offer completely new application areas, significantly enhanced product characteristics and considerable process optimization in industrial settings.

In 2011, bubbles & beyond has reached major milestones, including the launch of its enpurex® cleansing product line for the printing industry, an important global distribution agreement with Rolf Meyer GmbH for the enpurex® line, and a development collaboration with JNC-CHISSO to create advanced cleansing solutions for the microelectronics sector. In addition, bubbles & beyond has established an advisory board of seasoned industry experts.

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