News
Innovation Radar: Approved Drug Counters Effects of Alzheimer’s in Mice
An FDA-approved drug called bexarotene counters many of the effects of Alzheimer’s disease in mouse models, researchers report. The build-up of protein fragments called amyloid-beta is a key feature of the disease; everyone’s brain produces amyloid-beta, but in healthy individuals, enzymes break the fragments down, with help from a protein called ApoE. Paige Cramer and colleagues knew that bexarotene activates a protein that helps switch on the ApoEgene, and they hypothesized that the drug might therefore enhance the clearance of amyloid-beta in the brain. They gave the drug to mice engineered to have an Alzheimer’s-like condition and observed that levels of the protein fragments in the mice’s brains dropped substantially within just a few days. The mice also showed improvements in their cognitive, social and olfactory performance. Bexarotene, also known as Targretin, is currently used to treat a form of skin cancer and has a favorable safety profile, the authors note. The drug activates the nuclear receptor protein known as RXR, which binds one of two other nuclear receptors, PPAR and LXR. These receptor pairs then activate the transcription of the ApoE gene.
The research is published online by the journal Science at this week’s Science Express website.
Company News: Achmea and LSP Launch LSP-Health Economics Fund for Innovation in Healthcare
Dutch healthcare insurer Achmea and investment company Life Sciences Partners (LSP) have set up an investment fund for innovation in healthcare, the LSP-Health Economics Fund (LSP-HEF). On 5 September 2011, the healthcare insurer already announced its intention to make € 50 million available for this purpose. As of today, the fund is ‘open for business’ and will seek to invest in international technology companies that may contribute to increased healthcare quality and better cost control.
The fund will be managed by Life Sciences Partners (LSP) a pan-European investment firm specialized in healthcare and biotechnology investments. LSP has recruited a dedicated investment team consisting of investment and technology specialists as well as experts for health economics and healthcare processes. The team will target European and US-based companies that have products close to or on the market. The main focus are companies offering promising technologies or products targeting indications such as cardiovascular diseases, lung disease, diabetes, cancer and dementia – diseases that more and more people are afflicted with and for which society pays a high price.
New technologies and products for these indications can lead to better control of health care costs while improve the quality of patient care, for example by using better diagnostics, applying minimally invasive treatments or preventing complications. In spite of this, it is the experience of Achmea and LSP that many of these companies struggle to penetrate the market quickly due to an insufficiently developed health economics case; this is often due to the fact that the technology has not been developed together with healthcare providers, not all stakeholders have been considered, and that a sales process that requires addressing each individual physician can slow down market take-up.
Through the unique cooperation between an insurance company and an investment firm, Achmea and LSP can efficiently support such companies in bringing their technologies to the market. Achmea will provide access to its know-how, expertise and database to help build the healthcare economics cases. Moreover, Achmea will help companies to find their way in the healthcare market, and will bring new technologies to the attention of healthcare providers.
Food for Thought: Germany Lags Behind in Biotech
These days, everybody has his own opinion about the quality and prospects of the German biotechnology industry. It even seems to be difficult to determine if biotech funding in Germany has increased, remained stable – or dramatically decreased, as recently published by the German industry organization BIO Deutschland.
If you look at key intangibles, such as the extent of media coverage on the biotech sector and the attractiveness of German biotech companies for investment banks, it is obvious that German biotech is not on the rise.
An article by Roland Benedikter and James Giordano published by German newspaper Die Welt suggests a bleak scenario if Germany is not willing to accelerate and intensify its biotech efforts. According to the authors, biotechnology is not only the most important success factor in future economic development – it will also change the global power balance: “the one who controls the chips also controls the game”. Asia and the Far East are quickly catching up in the biotech space, while the U.S. and other European countries continue to heavily invest into the sector. Therefore, Germany might gradually evolve from an export-oriented country to an import-oriented one – unless there will be a fundamental change of mind in the German government and society.
Almost two decades ago, the German biotech industry started out with the clear goal to narrow the gap to the U.S., where biotechnological markets and ventures were (and still are) much more mature. Since then, the German biotech sector has successfully produced a number of promising companies, innovations and products. However, the most attractive and advanced companies and technologies have been acquired by foreign, mostly U.S.-based, companies. Amgen´s take-over of Micromet, an oncology company with academic roots at the University of Munich, is the most recent example.
Therefore, lack of innovation is clearly not the problem. And lack of funding is only the symptom of an underlying German (and partly European) biotech phenomenon – wide-spread risk aversion combined with limited availability of true executive leadership qualities. Moreover, the public sentiment towards biotechnological innovation remains skeptical or even hostile and is mirrored by a “we don’t need this”-attitude of politicians and even Germany’s healthcare system, in which IQWiG, a decision body responsible for drug reimbursement, does its best to belittle innovative medicines.
It may not surprise you that an often-heard German term, “technologiefeindlich” (i.e. a negative attitude towards technological innovation), lacks any English equivalents.
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.