Sanofi's MS-drug Alemtuzumab meets first primary goal
French drug maker Sanofi SA announced mixed results of a late-stage trial of multiple sclerosis drug Lemtrada. The two-year study CARE-MS I is the first of two randomised, Phase 3 clinical trials comparing Sanofi's alemtuzumab to Rebif. The CARE-MS I study incorporated 581 patients with relapsing-remitting multiple sclerosis who had not had prior treatment for their illness and showed that Lemtrada helped patients more than Rebif, Merck KGaA's established multiple sclerosis therapy. The product cut relapse rates by 55 percent over two years compared with Rebif Sanofi said in a statement on Monday. But Lemtrada failed on the second goal; statistically, it is not better than Rebif in helping stave off disability for the duration of the test. Sanofi's shares not unexpectedly fell after the announcement. Another Phase 3 clinical trial, CARE-MS II, is currently underway, evaluating Lemtrada against Rebif in relapsing-remitting multiple sclerosis patients who have relapsed while on therapy. The medicine’s prospects were at the heart of the Genzyme takeover talks this year. Cambridge, Massachusetts-based Genzyme was projecting peak annual sales of as much as $3.5 billion, saying Lemtrada was likely to become its bestseller. Sanofi said in October that analysts’ estimates of about $700 million were a valuation “probably closer to the reality of the product.” Sanofi expects to file the drug for U.S. and European Union approval in multiple sclerosis in early 2012 and has been granted fast track designation by the U.S. FDA. Sanofi has time. Cash is not the problem. On Monday the French drugmaker revealed it was selling its Dermik dermatology business to Canada's Valeant Pharmaceuticals for $425 million.
Graz – Austria is likely to lead the EU’s efforts to integrate existing national biobanks and associated data throughout Europe into a European biobanking infrastructure. The resource is aimed at reaching critical mass for the...
Graz – Austria is likely to lead the EU’s efforts to integrate existing national biobanks and associated data throughout Europe into a European biobanking infrastructure. The resource is aimed at reaching critical mass for the discovery of disease-associated biomarkers, which play a major role in the development of more targeted therapeutics that show fewer side effects. “The ministers of the member states, which will financially contribute to the BBMRI (Biobanking and Biomolecular Resources Research Initiative) through their national research budgets, are going to decide next year from where the biobanking hub will be coordinated”, said Prof Kurt Zatloukal from Graz Medical University, coordinator of BBMRI’s preparatory phase. Both the Netherlands and Austria had offerd to host the initiative, but according to Zatloukal, there is no direct competition. Within its short lifetime of one and a half years, the BBMRI has already mobilised more than 30 million euros. Zatloukal also stated that it is difficult to predict how many blood and tissue samples will be available through the BBMRI after its 5-year preparatory phase, as nobody knows at this time exactly how many governments will cooperate with funding from national budgets. To date, 51 partners and 210 associated partners from 31 nations have contributed to the preparatory phase. In mid-October, the Dutch gavernment allocated EUR 22.5M to BBMRI-NL, the Dutch arm of the BBMRI (see more). Following the announcemant , online news portals wrongly reported that the Netherlands will lead the BBMRI initiative.
In the fast-moving biotech sector, ethical frameworks always trail behind developments. Advances in fields like cloning, embryonic stem cell research, and biofuel production have mostly outstripped efforts to preview their...
here are several major hurdles to overcome in navigating the approaching ethical minefield. High on the list of these is defining what synthetic biology (SynBio) means exactly. At the round table debate sponsored by the European Commission on “Ethical Aspects of Synthetic Biology”, the Director of the Nuffield Council on Bioethics Hugh Whittall broadly defined SynBio as “the construction of novel biological networks/organisms with bespoke properties, using standardised biological parts that code for known functions.” These include “DNA sequences artificially designed and chemically synthesised in the lab, or genetic material from existing organisms,” while the field can “involve the redesign of existing systems, or the design of entirely novel networks.” This very broad definition of SynBio incorporates traditional genetic engineering techniques. The narrower interpretation that is likely to have more of an impact on public perception, however, is the “design of entirely novel systems”. In other words, genomes that are made to order, custom-built from scratch in the lab, and inserted into a chassis-cell to perform a specific desired function – real artificial life.
Moving at breakneck speed
The ethics of the debate have been given a fresh urgency by recent developments. The grand old man of biotech Craig Venter once again caused an uproar in August by claiming “artificial life is just a few months away.” Researchers at his Maryland institute in the US (JVCI) that have worked on the problem since 2002 successfully transferred naturally-occurring genomes from one species of bacteria to another in 2007. Less than a year later, they built the 580,000 base-pair genome of a parasitic bacterium from scratch, providing proof of principle for whole-genome construction. There were subsequent difficulties, however, inserting the artificial genome into a chassis-cell. These now appear to be resolved after the researchers chemically methylated the DNA before insertion. With the problem of rejection by recipient cells out of the way, Ventner told The Times in August that he expects “the first synthetic species by the end of the year.” In another development that made less of a splash in the media but is no less important in terms of applying the technology, a Harvard team under George Church have come up with what is in essence a method of accelerated evolution. Described in the August 13th issue of Nature, multiplex automated genome engineering (MAGE) is a process that should prove a powerful tool for selection in fine-tuning enzyme production for efficiency. Until now, improving bioproduction organisms was complex and slow. With MAGE, the team selected for optimised lycosene synthesis in E. coli variants, and obtained a strain within three days that produced higher yields than have ever been achieved industrially. Together, these two announcements promise very rapid development in SynBio, with MAGE providing a fast, powerful tool for the optimisation and selection of synthetic genomes. Genetically engineered or wholly synthetic microorganisms and protocells would be useful in a huge range of applications. They could be used to increase yields of medicines in biopharmaceutical production, clean up contaminated sites, revolutionise the fuel industry, and produce significant amounts of high-potential substances such as chemicals or spider silk. Unfortunately, while SynBio has enormous potential, there is no denying that it also comes laden with a number of potential risks.
Biosafety and security issues
The big questions involving SynBio and biosafety are not new ones. They are closely related to those in the GMO debate, and largely revolve around the unknowns of genetic transfer and risk assessment of ecological impact on the environment. However, there is a serious concern that widespread use of SynBio organisms in industry would make access to the technology easy, and that creating a synthetic killer-pathogen would be no more technically difficult than building a bacterium to clean up the environment. The risk of a terrorist attack with genetically engineered or synthetic life bioweapons is not immediate, as the necessary technology for producing and developing them is still very advanced. It is not beyond the means of governments however, and many commentators are more worried about state-sponsored use of the technology than they are about the threat of terrorists building bioweapons, or the rise of what Whittall calls ‘garage biology’. Although some patchwork regulatory frameworks are currently in place, most experts agree they are inadequate. If the public is going to embrace the technology, then it must first be convinced that it doesn’t pose a threat. And that confidence can only be earned by a strong international body dedicated specifically to the task.
Whose genes are these?
The question of who owns genes is a loaded one, and synthetic biology is certain to throw intellectual property issues even more into the limelight. Europeans have generally tended to view the patenting of organisms and genes as ethically questionable, while in the US acceptance of the concept is wider. The JVCI has already applied for a the rights to a sequence it claims represents the minimal requirements for life – a genome it calls Mycoplasma laboratorium – as well as other broader patents covering the creation of synthetic genomes and the methods used to transplant them into chassis-cells. Analogous to the cross-Atlantic divide on GMOs, Europe and the US could soon face a similar ethical parting of the ways when it comes to ownership of genomes. And this is far from the only area where societal differences could make a key difference in who eventually ends up with the biggest piece of the SynBio pie. According to a study conducted by Eleonore Pauwels, a Research Scholar from the Woodrow Wilson International Center who also spoke at the round table proceedings, the United States already has a formidable lead in terms of the resources being poured into the field. More than 200 entities and 100 universities are currently active in SynBio research in the US, compared to just 35 in the EU. Even more telling is the amount of money being thrown at the research. To date, American institutions and businesses have pumped in around US$1bn. In Europe, just a30m have been invested to date.
Learning from past mistakes
Individual EU member states are also making efforts to come to grips with SynBio issues in advance. A position paper published this summer by the German Research Association (DFG) in cooperation with two of the country’s other most prestigious research institutes is an attempt to avoid past blunders. DFG spokesman Marco Finetti said it was aimed at “an early attempt to position (the technology) to prevent skewed public opinion”, while one of the paper’s authors, Mannheim University professor Jochen Taupitz, said its aims included avoiding “the communications disaster that agribiotech turned into...as well as the unrealistically positive representations proclaimed by researchers asking for funding.” At the EU level, the round table debate and subsequent publication of the proceedings under the title “Ethical Aspects of Synthetic Biology” are a step towards coming to grips with the same issues. It’s a tricky task in Europe, but one that is vital if the EU is to take the helm this time around, instead of missing the boat yet again. B
Tumour immunotherapy specialist BioPheresis GmbH (Heidelberg) has appointed Dr. Niels Emmerich as its new Chief Executive Officer. The immunologist co-founded immatics biotechnologies GmbH, and served as the company´s COO until...
Tumour immunotherapy specialist BioPheresis GmbH (Heidelberg) has appointed Dr. Niels Emmerich as its new Chief Executive Officer. The immunologist co-founded immatics biotechnologies GmbH, and served as the company´s COO until 2009. Prior to his appointment at immatics, Emmerich was a strategic management consultant at McKinsey & Company.
Dublin/Boston – The risk-benefit ratio of Biogen/Elan’s co-marketed multiple sclerosis antibody drug Tysabri (natalizumab) is to be reviewed by the EU’s regulatory authority EMEA. The EMEA said on Friday that it has observed a...
Dublin/Boston – The risk-benefit ratio of Biogen/Elan’s co-marketed multiple sclerosis antibody drug Tysabri (natalizumab) is to be reviewed by the EU’s regulatory authority EMEA. The EMEA said on Friday that it has observed a higher rate of the potentially lethal brain infection progressive multifocal leukoencephalopathy - or PML - than disclosed in the current drug label. The alpha4 integrin inhibitor Tysabri is considered the most important growth driver for both US biotech company Biogen Idec Inc and Ireland's Elan Corp Plc, with nearly $1bn annual revenue. The US Food and Drug Administration (FDA) confirmed that there had been 23 cases of PML since 2006, 10 more that the FDA had reported in September. This would increase the risk of acquiring PML, which is caused by an opportunistic brain infection with the JC virus, from under 1 in 1,000 to 1,42 in 1,000. The additional PML cases may increase the drug's risk profile and raise questions about the companies’ role in updating the market on Tysabri’s safety record. Biogen last provided an update on the number of PML cases in July, when it said 11 cases had been reported. The company admitted last week that the risk of PML does increase with time. Biogen shares fell 7.2% on Nasdaq after close of market; Elan shares dropped 17.5% on the New York Stock Exchange on Friday. Tysabri was temporarily withdrawn from the market in 2005 after being linked with PML. The treatment for relapsing remitting multiple sclerosis was reintroduced in July 2006 with stricter safety warnings. Analysts stated that it is improbable that the regulatory authorities will withdraw market authorisation, but said the worst-case scenario is likely to be a further drug holiday,
Little Chalfont/Fairfield - General Electrics has kicked off a “GE Healthymagination Fund” worth US$250m. The new equity fund is designed for global investment in high-tech enterprises developing innovative diagnostics,...
Little Chalfont/Fairfield - General Electrics has kicked off a “GE Healthymagination Fund” worth US$250m. The new equity fund is designed for global investment in high-tech enterprises developing innovative diagnostics, healthcare IT, and tools for biopharmaceutical development and manufacturing. The fund, aimed at supporting UK-headquartered GE Healthcare, will also support companies that are developing new business models and services. The new fund is part of GE’s $6 billion Healthymagination initiative aimed at improving the healthcare system. The fund targets three areas for investment: diagnostics (e.g. imaging, contrast agents, molecular diagnostics, patient monitoring etc.), healthcare IT (electronic medical records), R&D tools for biopharmaceutical development or stem cells, and technologies for the manufacturing of biologics.
Oxford – British gene therapy specialist Oxford BioMedica plc has reported positive interim results from its ongoing Phase I/II trial of ProSavin, a gene therapy for the treatment of Parkinson's disease. All treated patients have...
Oxford – British gene therapy specialist Oxford BioMedica plc has reported positive interim results from its ongoing Phase I/II trial of ProSavin, a gene therapy for the treatment of Parkinson's disease. All treated patients have shown further improvement in motor function, with a maximum improvement of 53% and an average improvement of 34% relative to patients' pre-treatment motor function. The company also published preclinical findings with ProSavin (Science Translational Medicine), that confirm that the treatment is safe and efficient in animals at the same concentration as used in humans. The company said that the excellent safety profile of ProSavin justifies further dose escalation. Oxford BioMedica is seeking regulatory approval to escalate directly to a 5 times dose level using a modified administration procedure that requires fewer needle tracks and thus reduces surgery time. Both the study's data monitoring committee and the company's scientific advisory board support this strategy. Enhancing the efficacy of ProSavin and reducing the surgery time could accelerate the overall development timelines, and expand market opportunities.
Leuven – Belgian public company NV has been given approval for ChondroCelect as the first Advanced Therapy Medicinal Product from the European Commission. TiGenix will now commercialise the treatment with in vitro expanded...
Leuven – Belgian public company NV has been given approval for ChondroCelect as the first Advanced Therapy Medicinal Product from the European Commission. TiGenix will now commercialise the treatment with in vitro expanded cartilage cells in the 27 countries of the European Union, as well as in Iceland, Lichtenstein, and Norway. The commercial launch of the cell-based therapy for the treatment of single symptomatic cartilage defects of the femoral condyle (the end of the thighbone) of the knee will be defined by reimbursement timelines. According to TiGenix, the first phase of the launch will focus on Germany, the Netherlands, the United Kingdom, and Belgium. A core commercial team is in place to support the efficient rollout of ChondroCelect in these markets, and the majority of the targeted orthopaedic reference centres have been given appropriate training. In the meantime, TiGenix has begun negotiations with local health insurance bodies on product pricing and reimbursement.
Brussels – UCB Pharma SA’s arthritis treatment Cimzia (certolizumab pegol), in combination with methotrexate (MTX), has received the green light from the European Commission. The PEGylated antibody, which targets tumor necrosis...
Brussels – UCB Pharma SA’s arthritis treatment Cimzia (certolizumab pegol), in combination with methotrexate (MTX), has received the green light from the European Commission. The PEGylated antibody, which targets tumor necrosis factor (TNF), has marketing approval as a treatment of moderate to severe active rheumatoid arthritis (RA) in adult patients who have not responded to disease-modifying antirheumatic drugs (DMARDs). The subcutaneously injected drug can be given as a monotherapy in case of intolerance or unresponsiveness to methothrexate. Most common adverse reactions belonged to the system organ classes infections and infestations, reported in 15.5% of patients on Cimzia and 7.6% of patients on placebo. The most serious adverse reactions were serious infections (including tuberculosis and histoplasmosis), malignancies (including lymphoma), and heart failure. A pooled analysis of the safety data demonstrates a low incidence of injection site pain (1.5%), and a low level of discontinuations due to adverse events.
Berlin – Germany has launched Europe’s first civil high-throughput screening facility for high-risk infectious agents within the framework of ERA-NET PathoGenoMics. The novel bio-safety level 3 (BSL3) unit at the Max Planck...
Berlin – Germany has launched Europe’s first civil high-throughput screening facility for high-risk infectious agents within the framework of ERA-NET PathoGenoMics. The novel bio-safety level 3 (BSL3) unit at the Max Planck Institute for Infection Biology in Berlin was inaugurated in mid-September by representatives from the German Research Ministry and the Max Planck Society. The next step will be to carry out functional RNAi screens in flu-infected host cells to find new targets and drug leads.
Circumventing microbial resistance
Identification of drug candidates against multi-resistant bacterial pathogens will also be a priority for the team of Max Planck researchers under Professor Thomas Meyer. Infectious diseases are still the world’s second most frequent cause of death in spite of improvements in hygiene, vaccination campaigns and further development of antibiotics. Researchers currently use two scientific strategies to nail down promising drug candidates. The hypothesis-driven approach focusses on the investigation of distinct virulence processes, while the global analysis approach employs high-throughput technologies and bioinformatics to identify the most critical factors in pathogenesis. The latter has been gradually gaining in importance. Within the framework of ERA-NET PathoGenoMics, the Max Planck Society and German Ministry of Education and Research (BMBF) have now kicked-off Europe’s first high-throughput screening facility for highrisk pathogenic agents. The BSL3 (biosafety level) unit comprises a screening robot, as well as the necessary periphery infrastructure such as molecular biological BSL3 labs and state-of-the-art high-throughput microscopy and read-out devices. Its prime purpose will be to conduct screens with bacterial pathogens causing plague, typhus, tuberculosis and other deadly diseases.
First project: RNAi screen against pandemic influenza
The recent flu pandemic has also led to an expansion of that brief. The institute is now preparing to screen for drug candidates against pandemic influenza and is searching support from the EU FP7 HEALTH programme. Targeting host-cell compounds The researchers will be testing a new strategy for overcoming the ability of flu viruses to change their phenotype, thus escaping current therapeutic regimes. Influenza A viruses exhibit intrinsic mechanisms for generating altered viruses: their genome consists of 8 genome segments that can be quickly re-assorted upon viral coinfections, a process called antigenic shift. Such viral recombinants exhibit severely altered surface structures, allowing them to slip under the immune system’s radar. Moreover, virus replication facilitates the generation of point mutations, giving rise to a steady ‘antigenic drift’ and viral escape mutants. Such viral escape mutants clearly hamper efficacy of available flu treatments, as existing anti-virals are directed against bona fide viral targets, which risks generating therapy resistance. The new project is aimed at benefiting from the fact that viral infection and replication intimately depend on factors provided by the host cell.
Focus on targets essential for the virus
The MPI team will target host cell factors that are dispensable for the host but essential for virus replication. Using high-throughput RNA interference technology, they will scan the entire human genome for critical determinants of infection. Identification of these determinants will lead to promising therapeutic solutions for the most important human virus infections. The approach can also be applied to other viral infections with pandemic potential, according to Meyer. “During the past few decades, new viral diseases such as AIDS, SARS and Nipah Virus Encephalitis have emerged. On top of that, known viral agents are in the process of changing their behavior and location because of i.e. climatic variations or international traffic.” Meyer is convinced that the new project represents a necessary and timely search for suitable targets and effective drugs against devastating infections that have high mortality rates.
Basel – Swiss drug manufacturer F. Hoffman-LaRoche has reported a full phase III data set suggesting that its HER2-targeting antibody drug trastuzumab (Herceptin) prolongs survival by more than 4 months in patients with gastric...
Basel – Swiss drug manufacturer F. Hoffman-LaRoche has reported a full phase III data set suggesting that its HER2-targeting antibody drug trastuzumab (Herceptin) prolongs survival by more than 4 months in patients with gastric cancer expressing high levels of the HER2 marker. The patient group on Herceptin plus Xeloda or intravenous 5-Fluorouracil and cisplatin survived 16 months on average versus 11.8 months for patients receiving chemotherapy alone. According to Roche, around 16% of stomach tumours express high levels of HER2. Based on the findings, Roche has submitted a label extension application with the EU health authorities for use of Herceptin in HER2-positive advanced gastric cancer. Roche has said that applications for label extension in other global regions will follow as soon as possible. The trial enrolled 549 patients with inoperable locally advanced, recurrent and/or metastatic HER2-positive gastric cancer. The primary objective of the study was to demonstrate superiority in overall survival of the Herceptin-containing treatment arm (dosage: 6mg/kg) compared to solely chemotherapy arm. The pre-planned interim analysis was triggered by the occurrence of 347 events. Secondary endpoints for the study included progression-free survival, overall response rate, duration of response, safety, and quality of life. In the ToGA study, no new or unexpected side effects were observed, according to Roche. Overall survival corresponded to a 26% reduction in the risk of death. All patients who were included in the Herceptin study had a median increase in overall survival of 2.7 months to 13.8 months. The response rate was increased with Herceptin from 34.5 % to 47.3%. Patients with tumours exhibiting higher levels of HER2 experienced even greater benefits from the inclusion of Herceptin
7th Berlin Conference on IP in Life Sciences: Big Data, Big Drugs
The health care industry faces significant transformation, driven by a boom in knowledge within biomedical sciences and breakthrough technologies such as gene sequencing. The management of "big data“ will change the understanding of diseases, development of drugs and treatment of patients. more