Next meeting ACTIP:

November 19-20, 2009, Leiden, The Netherlands

hosted by ACTIP member company DSM Biologics.The meeting will focus on ’manufacturing processes of the future’ and ’production of biosimilars’. For ACTIP member companies and invited observers only.

In this issue:
European News
Clinical trials and results
Regulatory News
Biomanufacturing News
Business News
Vaccine News
Collaborations and mergers
Research News
Stem cell news
Awards
Agenda

European News

Europe leads US in R&D productivity, says Health Affairs

Europe is pulling ahead of the US in research productivity, according to a controversial new study by Washington public policy think tank Health Affairs. The “Global Drug Discovery: Europe is Ahead” report, which is based on analysis of all new chemical entities (NCEs) approved between 1982 and 2003, suggests that, contrary to popular opinion, the US has never overtaken Europe in terms of research productivity. Author Donald Light argues that although studies like Graboski et al (1) purport to show that “US firms overtook their European counterparts in innovative performance,” his reanalysis of their data shows that it “actually document[s] the greater and increasing research productivity in Europe.”  Light also suggests that several European Commission studies focusing on the same period had reached the same conclusion “despite little solid evidence,” citing a 2008 study by Stolk et al (2) as the basis of his opinion.
Predictably, Light’s conclusions have not been warmly received in the US. Pharmaceutical Research and Manufacturers of America (PhRMA) senior vice president Ken Johnson issued a firm rebuttal of the idea that Europe is ahead. He said that: “Unfortunately, the paper paints a distorted picture that gives short shrift to the medical advances made possible by [US] pharmaceutical research and biotechnology companies and ignores the chilling effect of government price controls on such innovation.” “In the not-too-distant past, the US was not the world’s medicine chest. A number of changes, including Congressional action, helped to foster a more vibrant biopharmaceutical industry”. Johnson contrasted this with what he described as “European leaders’ embrace of ill-conceived public policies” which he said had “chilled innovation on that continent and raised doubts among private investors.”
The full PhRMA response can be viewed here .
H.G. Grabowski and Y.R. Wang. “The Quantity and Quality of Worldwide New Drug Introductions, 1982-2003,” Health Affairs 25, no. 2 (2006): 452-460.
19. P. Stolk and D.W. Light, “Did the U.S. Eclipse European Research Productivity? An Analysis of Major Reports as Searchlights in the Fog,” Report to TI Pharma Escher Project (Utrecht: University of Utrecht, 2008).
Source: www.In-pharmatechnologist.com, August 26, 2009

US 'reaping benefits' of EU education spending 

Europe is failing to capitalise on its investment in education and science because bright young researchers still see the US as the best place to further their career, according to Czech scientist Blanka Ríhová, Ambassador of 2009 European Year of Creativity and Innovation. In an interview with EurActiv Czech Republic, Ríhová said Europe needs to reward teachers and scientists better and must boost research spending if it is to keep its top talent. 
“Europe educates good university students and PhD students. These students study how to work in science, they are in close contact with new ideas and also with modern ways of solving scientific problems. It costs a lot of money but when we need to take advantage of these people, Europe starts to economise,” she said. 
Ríhová, herself a microbiologist and immunologist, said science graduates need to view Europe as a place where they can better themselves. “There are not enough opportunities or money for them. That’s why they leave. And the number one country they leave for is still the US,” she said. 
Working in the US provides a major career boost for young scientists and attracts top talent from Europe, Asia and elsewhere. “In this way, the US gets young people who are well prepared without investing a single dolar in their education,” Ríhová complained. 
She said mobility is a major problem for European researchers, where red tape makes it difficult to move to a new job outside your own member state. Ríhová said EU funds should be more flexible and must become pro-mobility in order to help complete the European Research Area. More respectable salaries could be another way to making researchers’ careers more attractive.
Source: EurActiv News, November 10, 2009

Barroso pledges to create European Chief Scientist role

Europe is finally to get a Chief Scientist with a brief to provide advice across the Commission. José Manuel Barroso recently made the pledge to newly elected Members of the European Parliament, as they met to rubber-stamp the renewal of his presidency.
“In the next Commission, I want to set up a chief scientific adviser who has the power to deliver proactive, scientific advice throughout all stages of policy development and delivery,” he said. Barroso added that this underlines “the central importance” that he attaches to research and innovation.
Barroso also committed to inject more scientific objectivity into policies to deal with climate change, saying he will set up a Commissioner for Climate Action to reflect the fact this, “is a challenge that needs to be addressed across the whole range of our policies.”
Barroso also promised investment in new sources of sustainable growth and the building of “networks of the future” ranging from digital infrastructure, to supergrids for electricity and gas. “We cannot and must not return to the previous growth model: it has clearly proved unsustainable. We have to create the conditions where the transition to a low carbon economy is a source of competitive advantage for business, a source of jobs for workers and a source of hope for future generations,” Barroso told MEPs.
Source: BulletinScienceBusiness.net, September 17, 2009

New EU website goes live 

On September 21, the European Commission has launched a revamped version of its Europa website. After two years of analysis and review, the EU executive hopes its new central web portal will make for a simpler, more organised experience for EU citizens.
As reported by EurActiv, the current site is considered by EU officials to contain “too much information" and Europeans navigating the portal find it "hard to know where to start looking" (EurActiv 14/07/09). 
Indeed, when DG Communication (DG COMM) officials in 2008 asked Ernst & Young to evaluate whether the Europa portal satisfied the objectives set out in the Commission's Internet strategy, the consultants concluded that the website was “too unorganised and too complex to navigate," and the EU executive was "not clearly targeting" its main audience. 
Following a comprehensive restructuring process, the Commission has simplified Europa's layout, dividing the site into six main themes reflecting users' needs. 
The first stage of these updates will apply to the DG COMM pages. According to the expert, “their hope is that the other DGs will be inspired to improve their own areas. DG COMM certainly seems to believe that other high-level people involved in this process realized that their parts of the site needed to change”. 
Source: www.EurActiv.com, September 21, 2009

Clinical trials and results

ACRO wants trials for most biosimilars

In a letter sent to the US Senate, the Association of Clinical Research Organisations (ACRO), which claims to represent firms conducting trials in 115 countries worldwide, recommended that while a 12-year exclusivity period for innovative drugs is important for R&D, US legislation should include rules on trials for biosimilars. The approval of biosimilars is currently a topic of hot debate in the US with the main focus of argument being the length of the market exclusivity period awarded to such medications.
In the letter, the organisation said that: “While the data exclusivity period is of great importance, we view the approval process for biosimilars to be of at least equal importance and the statutory pathway for approval should not be overlooked in the legislation to reform the US health care system.” The ACRO recommends that clinical testing be required for the approval of all biosimilars unless the Food and Drug Administration (FDA) waives such trials and advises that the same efficacy, purity and immunogenecity standards required of innovator drugs be demanded of all generic biologics. It also believes that “the data requirements for approval of a biosimilar may be reduced if there is a scientific basis to do so but the data quality must be at the same level as the innovator product and patient welfare must not be compromised.
The full ACRO letter can be read here .
Source: In-pharmatechnologist.com, October 15, 2009

Positive Phase I results for BI-204 in patients with elevated LDL cholesterol

BioInvent International AB (OMXS:BINV) announced that its therapeutic antibody product candidate BI-204 (anti-oxLDL), has reached the primary endpoint in its Phase I trial, and was safe and well tolerated. The objectives of the double-blind, within-group randomised dose-escalation trial were to determine the safety and tolerability of BI-204, as well as evaluation of pharmacokinetic parameters in order to help set dosage of the drug in future Phase II trials. Pharmacokinetic results showed the half-life was in the expected range for fully human antibodies. The study, conducted in Denmark, involved a total of 80 healthy patients with elevated LDL cholesterol. The drug is being co-developed with Genentech, Inc., a wholly-owned member of the Roche Group, under an agreement signed in January 2007. Under the terms of the agreement, Genentech obtained commercialization rights for North America while BioInvent has retained the rights for the rest of the world.

BI-204 is a human antibody derived from BioInvent’s proprietary antibody library n-CoDeR®. The antibody targets oxidised forms of a lipoprotein (apoB100), which is a component of the LDL particle. In preclinical studies it has reduced inflammatory processes and plaque formation significantly. It is being developed as a potential drug for secondary prevention of cardiac events, such as death, heart attack or stroke, in high-risk patients.
Source: BioInvent Press Release, May 6, 2009

Herceptin gives unprecedented survival benefit in HER2-positive stomach cancer

Data from the ToGA study presented at the American Society for Clinical Oncology Annual Meeting in Orlando, Florida showed that adding Herceptin (trastuzumab) to standard chemotherapy (Xeloda or intravenous 5-FU and cisplatin) prolongs the lives of patients with this aggressive cancer on average by nearly three months to 13.8 months. Advanced stomach (gastric) cancer is associated with a poor prognosis; the median survival time after diagnosis is approximately 10 months with currently available therapies. 
Source: Roche Group Media Relations, May 31, 2009

Start phase III trials to lower cardiovascular risk in high-risk diabetes patients

Roche announced it will start Phase III clinical investigations for aleglitazar, its innovative PPAR co-agonist R1439 which is uniquely designed to reduce cardiovascular morbidity and mortality in high risk patients with type 2 diabetes. This decision is supported by data from the Phase II SYNCHRONY study published in The Lancet and announced at the American Diabetes Association (ADA) in New Orleans, US. The phase III programme is anticipated to start in the second half of 2009.
SYNCHRONY, a placebo-controlled dose ranging study in type 2 diabetes patients, showed that aleglitazar had a balanced synergistic effect on both lipid and glucose control with a good safety and tolerability profile in patients with type 2 diabetes.
Source: Roche Group Media Relations, June 9, 2009

BioInvent to start Phase I Trial for BI-505 in Multiple Myeloma

BioInvent International AB has received clearance from the U.S. Food & Drug Administration (FDA) to initiate a Phase I open dose-escalation study with its therapeutic cancer antibody BI-505 in patients with advanced Multiple Myeloma.
The Phase I study will investigate safety, pharmacokinetics, pharmacodynamics, and will aim to define the optimal biological dose of the antibody for phase 2 drug development. BioInvent will recruit approximately 40 patients with advanced Multiple Myeloma across 3 centres (possibly extending to 4) in the U.S. as part of the study.
BI-505 is a fully human antibody derived from BioInvent’s proprietary n-CoDeR® library and targets the adhesion molecular ICAM-1 leading to cell death. ICAM-1 is highly expressed in several tumours but is not widely expressed in normal tissue. Preclinical results have demonstrated that the compound is more efficacious to fight tumours than existing drugs. BI-505 has been granted orphan drug designation in the U.S. and Europe for the indication of Multiple Myeloma.
Source: BioInvent Press Release, August 11, 2009

Good progress with the  Phase II trial of the long acting anticoagulant TB-402

BioInvent International AB (OMXS) announced that it has started recruitment of the third and final cohort of 100 patients for the Phase II trial of TB-402, a drug being developed for the prevention of deep vein thrombosis. The first two patient cohorts included in total 200 individuals and the recruitment for the second cohort was concluded in August. The decision to start recruitment of the third patient cohort follows an unanimous recommendation from the external board monitoring the efficacy and safety of the study.
The Phase II trial is an active (enoxaparin)-controlled, dose-escalating, multicenter, prospective, randomised, open label trial evaluating TB-402 for the prophylaxis of DVT after knee surgery. The study will assess three different doses of TB-402 given as a single intravenous injection post knee replacement surgery and the trial will enrol 300 patients. The objective of the study is to assess the safety and efficacy of the three escalating doses of TB-402. All the patients in the study will be monitored for a period of three months after surgery. TB-402 is developed in collaboration with ThromboGenics NV.
Source: Press Release BioInvent, September 23, 2009

Studies show promise for patients with malignant melanoma

Results from the phase II BEAM study investigating use of Avastin plus chemotherapy in patients with malignant melanoma demonstrate that Avastin may have the potential to improve progression-free survival (PFS) and overall survival (OS) in this deadly disease. The primary endpoint of progression free survival showed a 22% risk reduction for progression in Avastin treated patients in this Phase II study. Overall survival, a secondary endpoint, showed an improvement in median overall survival of three months, a 21% risk reduction of death. These data are encouraging and warrant further investigation.

In a phase I extension study of previously treated melanoma patients who harbour the BRAF mutation, 70% experienced shrinkage of their tumours when treated with PLX4032, a BRAF selective inhibitor.
Results from both studies were presented at the joint ECCO 15 and ESMO 34 congress.

In another phase III study with Avastin (in early stage colon cancer), it emerged that the addition of one year of Avastin to chemotherapy did not result in a statistically significant improvement in overall disease-free survival (DFS). However, during the year of Avastin treatment there was an early and significant improvement in disease-free survival that diminished over the course of the study.
Finally, a Phase III (ATLAS) study in patients with advanced non-small cell lung cancer who received Avastin (bevacizumab) and Tarceva (erlotinib) as combined first-line maintenance treatment had a 39 percent improvement in the time they lived without the disease advancing (progression-free survival or PFS, the primary endpoint of the study), compared with those who received Avastin alone. This ATLAS study was stopped early because of the superior efficacy for patients in the combined treatment group. 
Source: Roche Group Media Relations, September 23, 2009 and May 30, 2009

Gene therapy for Parkinson's "encouraging" in early trials

A gene therapy for Parkinson's disease that has been tested on lab monkeys is showing good early results in a small-scale trial on humans. The therapy entails taking three genes that produce dopamine, a key neurochemical that is depleted in Parkinson's. The genes are then inserted into a disabled equine virus that is then injected into the brain.
Six human volunteers began clinical trials a year ago, and the results are "extremely encouraging," as measured in control of Parkinson's symptoms and in side effects such as brain inflammation.
Another half-dozen volunteers are going to be recruited into the trial. If all goes well, a so-called Phase III trial, involving a large number of patients to assess the treatment for safety and effectiveness, would start from 2013.
The tentative trials on humans were authorised after three and a half years of experiments on macaque monkeys that had been given neurotoxins to replicate Parkinson's syndrome. The gene therapy, called ProSavin, restored the monkeys’ levels of dopamine, corrected motor problems and prevented dyskinesias, as jerkiness, rigidity and tremor are called. There was "80 percent recovery" among the animals, "and the results were stable for up to 44 years after treatment," said fellow neurosurgeon Bechir Jerraya.
Source: Cordis Simple Search, October 14, 2009

ACTEMRA inhibits progression of joint destruction in RA patients by over 80%

Two-year data from the LITHE study, recently presented at the American College of Rheumatology, show that, with long-term use, patients with rheumatoid arthritis treated with ACTEMRA (tocilizumab, known as RoACTEMRA within the EU) plus methotrexate (MTX) suffered 81% less damage to their joints compared to those treated with MTX, the current standard therapy, alone. For patients, this means that their joint damage is significantly reduced, and that they can therefore continue to enjoy their lives without the evolving disability usually associated with the disease. more
Source: Roche Press Release, October 17, 2009

Regulatory News

South Africa pledges to speed access to new medicines

The South African government has announced moves to clear the massive backlog of drug approvals and develop a recovery strategy for the pharmaceutical industry. The backlog has occurred “due to an unexpected increase of submissions by the pharmaceutical industry for the registration of medicines during the previous three years,” says the regulator, the Medicines Control Council (MCC), adding that the scope of the problem was revealed by the Medical Products Task Team set up by Health Minister Aaron Motsoaledi to identify priority areas in health care that require “immediate attention.” As a result, the MCC is asking all manufacturers for information on drug registration applications which are still in the approvals pipeline.
 
The MCC’s 12 million rand (£990,000) backlog clearance project, which is being undertaken with funding from the UK's Department for International Development (DFID), has been welcomed by the multinational drug industry association, Innovative Medicines SA (IMSA). Currently, the approval process takes up to four years and more than 2,000 applications are now stuck in the pipeline, says IMSA. Moreover, of the 3,731 applications for both originator and generic product approvals submitted to the MCC during 2003-7, only 2,428 — or two thirds — received approval.

The major drawback currently confronting the industry is price controls, while regulatory delays and a lack of incentives for investors are also a problem, but the government has targeted the sector as a priority for development, with the aim of boosting domestic production and reducing reliance on exports.
Source: www.PharmaTimes.com, September 23, 2009

ASEAN GMP audit sharing a step to EU-like single market

The Association of Southeast Asia Nations’ (ASEAN) member states will recognise each others GMP certificates as part of a programme intended to raise standards and eliminate trade barriers.
Signing of the sectoral mutual recognition agreement (MRA) is viewed by the member states as an important step in the plan to form the ASEAN Economic Community, similar to the European Union single market, by 2015.
The 10 ASEAN member states, which include Singapore, Vietnam and Malaysia, have until January 1 2011 to implement the MRA. Once in place good manufacturing practice (GMP) certificates and inspection reports issued in one of the 10 countries will be used by all member states.
These reports will be used by countries as the basis for granting approval to the manufacturer, supporting post-market assessments and as a source of information about a company’s facilities.
Included in the report will be details of the dosage forms manufactured at a facility and whether it is compliant with GMP. The MRA states that facilities should be “regularly inspected”, although no timeframe is given, and puts measures in place to ensure members have confidence in each others standards.
One aspect of this is that regulatory bodies: “must regularly monitor their respective inspection services to ensure that the latter are capable and remain capable of properly assessing manufacturers.”
This is intended to ensure that standards remain high and other countries have the opportunity to monitor the effectiveness of this through collaborations, such as joint audits or inspections.
By implementing the MRA the ASEAN is hoping to ensure safety, standards and efficacy, reduce the need for repetitive testing and enhance the competitiveness of manufacturers.
Source: In-pharmatechnologist.com, April 15, 2009

FDA approves high titre manufacture of Tysabri

The FDA has approved Biogen Idec to manufacture Tysabri using a high titre process but the product’s sales have been “negatively impacted” by the cases of patients developing PML.
Tysabri (natalizumab) was pulled from the market for 18 months in 2005 because of a suspected link to progressive multifocal leukoencephalopathy (PML), a rare brain infection. The product was reintroduced in July 2006 and since then there have been six reported cases of PML.
This is within the ratio detailed on the drugs label but Biogen still believes the PML concern is hindering growth. Despite this sales of Tysabri rose 44 per cent in its latest results and the US Food and Drug Administration’s (FDA) approval of the high titre process is a further boost for the product.
Biogen also received approval of the high titre process from the European Medicines Agency (EMEA) in December.
Source: www.In-pharmatechnologist.com, April 20, 2009

Glioblastoma newly approved indication of Avastin

Roche announced that the US Food and Drug Administration (FDA) granted accelerated approval of Avastin (bevacizumab) for people with glioblastoma with progressive disease following prior therapy. The new indication for Avastin was granted under the FDA’s accelerated approval program that allows provisional approval of medicines for cancer or other life-threatening diseases. It follows the unanimous vote by the FDA Oncologic Drugs Advisory Committee (ODAC) on March 31st.
 
“People with this type of brain cancer have had no new treatments in more than a decade,” said Timothy Cloughesy, M.D., director, Neuro-Oncology Program of the Jonsson Comprehensive Cancer Center at the University of California, Los Angeles. “After so many years with little progress in this field, Avastin was associated with a durable tumor response and doctors now have a new medicine to offer patients.”
Source: Roche Media Group Relations Press Release, May 6, 2009

Avastin approved for common type of kidney cancer

The U.S. Food and Drug Administration (FDA) has approved Roche’s Avastin (bevacizumab) plus interferon alpha for people with metastatic renal cell carcinoma, the most common type of kidney cancer. According to the American Cancer Society, kidney cancer is the eighth most commonly diagnosed cancer in the United States. In 2009, approximately 13,000 Americans will die from the disease.
Commenting on the approval, William M. Burns, CEO of Roche’s Pharmaceuticals Division said, “Avastin has now been approved for five different types of cancer in the USA. This underscores our belief in the important clinical benefits that Avastin delivers as we push forward with our ongoing research programs in more than 30 tumour types.” more
Source: Roche press release, August 3, 2009

First marketing authorisation for an advanced therapy medicinal product

The European Medicines Agency has recommended the first marketing authorisation for an advanced therapy medicinal product (ChondroCelect), following a positive opinion from the Agency’s Committee for Advanced Therapies (CAT) and the Committee for Medicinal Products for Human Use (CHMP).

ChondroCelect, from TiGenix NV, is a cell-based medicine that is used to repair defects in the cartilage of the femoral condyle (the end of the thighbone) in the knee. It consists of chondrocytes (cartilage-forming cells) that are taken from a healthy region of the patient’s cartilage, grown outside the body, and then re-implanted during surgery.
ChondroCelect is the first product to benefit from the new legal and regulatory framework for advanced therapy medicinal products (Regulation (EC) No 1394/2007).

The CAT, a multidisciplinary committee bringing together some of the best available experts in gene therapy, somatic cell therapy and tissue engineering, assessed the scientific data provided to support the marketing authorisation application for ChondroCelect. In line with the procedure set out by the Regulation on advanced therapy medicinal products, the CAT prepared a draft opinion, which was forwarded to the CHMP. On the basis of this opinion, the CHMP adopted its recommendation that ChondroCelect be granted marketing authorisation on 25 June 2009.
As part of the application, the CAT and the CHMP have required the company to submit a risk management plan with a series of measures, including further studies to ensure that the medicine’s efficacy and safety are followed up in a robust manner once it is on the market.
The scientific recommendation will now be forwarded to the European Commission for the adoption of a legally binding marketing authorisation decision.

More reading: 
1. A summary of opinion for ChondroCelect with the full indication is available here: http://www.emea.europa.eu/pdfs/human/opinion/ChondroCelect_38336609en.pdf
2. More information about the Agency’s work in the field of advanced therapy medicinal products can be found here: http://www.emea.europa.eu/htms/human/advanced_therapies/intro.htm

Source: EMEA Press Release, June 26, 2009

EMEA recommends authorization of two vaccines for influenza pandemic (H1N1) 2009

The European Medicines Agency has recommended to the European Commission that two vaccines against influenza A(H1N1) (‘swine flu’) be granted a marketing authorisation.
The vaccines concerned are Focetria (Novartis) and Pandemrix (GlaxoSmithKline). Decisions on the granting of European Union-wide marketing authorisations for the vaccines by the European Commission are expected shortly. Vaccination strategies are decided by the government in each EU Member State, taking into account the information provided by the Agency for each vaccine.

The Committee is currently recommending a two-dose vaccination schedule, at an interval of three weeks, for adults, including pregnant women, and children from six months of age. The Committee acknowledged that there are preliminary data suggesting that one dose may be sufficient in adults. The Agency is expecting further data from ongoing clinical studies over the coming months and these recommendations may be updated.
Focetria and Pandemrix were authorized using the so-called ‘mock-up’ approach. This approach allowed development and authorization of these vaccines in advance of the pandemic, based on information generated with a different virus strain that could have caused a pandemic (an H5N1 influenza virus strain). Once the A(H1N1)v virus strain causing the pandemic was identified by the Word Health Organization, the manufacturers were able to include it in the mock-up vaccines to prepare final pandemic vaccines.
Decades of experience with seasonal influenza vaccines indicate that insertion of a new strain in a vaccine should not substantially affect the safety or level of protection offered. The Committee’s recommendation to authorise these two vaccines is based on the information on the quality, safety and immunogenicity, including information on clinical trials in more than 6,000 subjects, generated at the time of the authorization of the mock-up vaccines, as well as on information relating to the change in strain from H5N1 to H1N1.
Further clinical trials in adults and in children are ongoing and more results will become available from October/November 2009 onwards.

The vaccines recommended for authorisation, Focetria and Pandemrix, contain ‘adjuvants’ (substances that enhance the immune response so that less viral material can be used in each dose of vaccine). They are widely used in vaccine manufacture and have a good safety record. The adjuvant in Focetria has been used in another flu vaccine since 1997 in more than 45 million doses. The adjuvant in Pandemrix has been tested in clinical trials involving several thousand subjects.
Source: Press Release EMEA, September 25, 2009

Fast EU approval of Baxter’s H1N1 Flu Vaccine anabled by EMEA’s mock-up licensure process

The European Commission sanctioned Baxter’s Celvapan H1N1 pandemic flu vaccine, produced using its Vero cell technology. The company claims the vaccine is the first cell culture-based, non-adjuvanted pandemic flu vaccine to get EU clearance.

Baxter is currently carrying out clinical trials of Celvapan H1N1 and said that it will supplement the licensure post-approval with additional clinical program data. The company will also provide the EMEA with immunogenicity data from the first vaccination in adults within the next few days. The current dosing schedule specified in the agency’s mock-up licensure for Celvapan using another virus strain involves two 7.5 microgram doses, given 21 days apart. Baxter said a trial in healthy adults will indicate whether a single dose may be enough for the Celvapan H1N1 vaccine. The trial will also determine whether a lower, 3.75 microgram dose is sufficient to induce the required immune response.
The EMEA implemented its mock-up licensure regulatory pathway for pandemic vaccines in 2004. The pathway allows companies to develop, evaluate, and register a pandemic vaccine candidate using an available influenza strain that has the potential to cause a pandemic. Once a flu pandemic occurs and the responsible strain is isolated, the mock-up licensure process allows for fast-track approval of the vaccine containing the actual pandemic strain.  Baxter was granted mock-up licensure for Celvapan using a different strain earlier this year. This vaccine was tested internationally through five completed clinical trials. The company received the causative pandemic H1N1 strain from the U.S. CDC in May and undertook preproduction testing and evaluation to assess the strain’s growth characteristics in the Vero cell culture technology. Commercial production was then started in early June, and Baxter initiated its license application for the final Celvapan H1N1 vaccine in July. Bulk Celvapan H1N1 vaccine is now produced at Baxter’s facility in the Czech Republic and is subsequently sent to Austria for final formulation, fill, and finish.
Related reading:
H1N1 Swine Flu Activity Picks Up; Vaccine Roll-Out Under Way (Oct. 4, 2009)
FDA Okays Vaccines for 2009 H1N1 Influenza Virus (Sep. 16, 2009)
H1N1 Influenza vaccine manufacturers ramp up for October 15 (Aug. 19, 2009)
H1N1 Pandemic Is Here but Moderate in Severity (June 15, 2009)
Baxter Receives Austrian Preparedness Contract for Pandemic Influenza Vaccine (Nov. 22, 2006)
Source: GEN News Highlights, October 7, 2009

Biomanufacturing News

Protein therapeutics expected to be worth $77bn by 2011

The global protein therapeutics market will be worth $77bn by 2011, with biogenerics playing an increasingly important role, according to a new survey by industry analysts RNCOS.  The report, “Global Protein Therapeutics Market” forecasts that growth of the sector, which expanded 14 per cent in 2008, will be driven by the pharmaceutical industry’s efforts to replace revenue lost as traditional small molecules drugs go off patent. The authors suggested that although monoclonal antibody type drugs will continue to be the biggest sellers, demand for novel medications like insulin, beta interferon, G-CSF and coagulation factors will grow considerably over the next few years.
The report also highlighted the potential of the biogenerics market, which they predicted will generate annual revenue of $3bn a year driven by growing demand for low cost versions of protein drugs. The authors also predicted that: “much of the growth will be driven by European and Asian countries in near future, as they have already approved the regulatory pathways for biogenerics.”
In addition, within the pharmaceutical industry as a whole, the contract manufacturing sector is likely to be one of the key beneficiaries of the protein therapeutics and biogenerics markets. The growth of the outsourced manufacturing sector in the last few decades has been dramatic as pharma firms have increasingly turned to third parties to reduce spending. The last 18 months has seen a considerable increase in this sort of activity as the global economic downturn has intensified the pressure on pharma firms to reduce costs. While this has allowed pharmaceutical firms to reduce spending, it has also meant that a considerable amount of in-house manufacturing capacity and expertise has been lost. As a result the drug industry’s reliance on third parties has increased. RNCOS contention is that a pharmaceutical industry now comfortable with the idea of outsourced manufacture is likely to seek the same sort of service for the production of protein therapeutics and biologics.
Source: www.In-pharmatechnologist.com, August 25, 2009

Tobacco used for cheap, quick vaccine production 

Researchers claim tobacco plants provide an economical method of manufacturing norovirus vaccine, a product that would have low profit margins, and achieve commercial scale in two to four months.
The research was presented by Charles Arntzen at the national meeting of the American Chemical Society (ACS). Arntzen explained that using tobacco plants quantities for clinical trials can be ready in eight to 10 weeks, with commercial scale being achieved within four months. Genetically modified tobacco mosaic virus was used to infect the plants, turning cells into norovirus vaccine factories. This method has been used by other researchers and is increasingly recognised as a cheap, quick way of producing a therapeutic. The next stage in development of the norovirus vaccine is to decide on the formulation and dosage to use in clinical trials. Nasal administration is more effective, according to Arntzen, and a formulation using a mucoadhesive is being investigated. This is a dry powder formulation containing the mucoadhesive that makes the treatment stick to the nasal passages. Patients are unable to feel the powder in their nostrils. Arntzen described the formulation as “very, very effective” and the intellectual property of the delivery method is now being investigated. Once these stages are complete Phase I trials will begin using funding from the US National Institutes of Health (NIH).
Norovirus is not life threatening and has limited market potential and this is why big pharma is yet to produce a vaccine for it, according to Arntzen. However, tobacco plant based production could cut costs and make the vaccine economically viable. The reasoning for this is that norovirus vaccine will probably be purchased by consumers, as opposed to prescribed by doctors, so costs must be kept low. Travellers, the military and hospital staff were suggested as potential users of the vaccine, which would provide immunity against the virus that causes diarrhoea and vomiting.
Source:  www.In-pharmatechnologist.com, August 20, 2009

Bayer sets up tobacco plant drug production facility

Germany's Bayer hopes that its pilot-scale production facility in Halle, Saxony-Anhalt will help establish its tobacco plant-based expression system as leader of the lucrative protein manufacturing sector. While protein synthesis using transgenic plants like maize, tobacco, oilseed rape and soya is at an advanced stage of development, conventional methods require the creation and maintenance of crop strains that contain genetic material that encodes the desired protein. Bayer's process, which was developed by Icon Genetics prior to its acquisition by Bayer in December 2005, utilises a virus-based mechanism to transfer the desired DNA sequences to the tobacco plants in order to expedite the protein production process, and remove the need to develop transgenic plant strains.
Bayer's technique uses high-yield tobacco plants produced in a rich growth media containing a modified version of the bacteria Agrobacterium tumefaciens that has been implanted with a tobacco mosaic virus (TMV) containing DNA encoding the desired protein. The virus infects the tobacco plants, injecting its genetic material into the nucleus of the plant's cells where it is expressed when they are subsequently retuned to the Halle facility's greenhouses. The advantage of Bayer's technique is that because the DNA sequences can be rapidly transferred to wild-type tobacco plants, no potentially time consuming crop development steps are necessary. While the tobacco plants eventually lose the recombinant DNA as the TMV infection runs its course, a batch production process can be implemented to ensure that there are always plants available. In addition, because genetic manipulation of TMV is a relatively straightforward and established technique, Bayer's approach could be readily adapted to produce a wide range of proteins in a relatively short period of time.
Bayer's SFF gains EMEA approval
Source: www.In-pharmatechnologist.com, June 18, 2009

Contract to develop high cell densities bacterial expression systems
Xcellerex, Dowpharma, Biopharm Services, and deltaDot have been awarded $11 million to develop technology that accelerates mAb and vaccine manufacturing. DTRA’s Joint Science and Technology Office, Transformational Medical Technologies Initiative granted the phase 2 funding.
The 12-month phase 1 contract was received from DARPA. The initial stage of the program was aimed at developing a high-efficiency bacterial-expression system using Dowpharma's Pfenex Expression Technology™ in conjunction with Xcellerex’ single-use FlexFactory platform to grow production strains to high cell densities and to purify the model vaccine and antibody.
The current effort will work to increase the productivity and speed of process optimization, including demonstration of scale-up and improved economics. This will include optimizing host strains and a manufacturing process required to increase the yield of vaccines and mAbs by 10-fold over that achieved in phase 1 with the added objective of increasing product quality.
Source: GEN News highlights, March 24, 2009

Pfizer inaugurates new $214m Swedish biotech plant

Pfizer's new $214.8 million (€150m) biotechnology facility in Strangnas, Sweden was inaugurated on August 25. The new 6,000 sqm plant will be used to make active pharmaceutical ingredients (API) for Pfizer's human growth hormone (HGH) drugs Somavert (pegvisomant) and Genotropin (somatropin [rDNA origin]) when fully operational in 2011. A key focus of the plant will be growth of the bacteria Escherichia coli (E.coli) and yeast for the production of recombinant proteins. However, Pfizer also stressed that the facility was designed with flexibility in mind, explaining that the production of multiple biotechnology drugs is an option.
Source: In-pharmatechnologist, August 26, 2009

Lonza expands Cell Therapy production into Asia

Lonza is bolstering its cell therapy manufacturing capabilities with the construction of a facility at the Tuas Biomedical Park in Singapore. A CHF 30 million, or about $27 million, investment is being made into the first phase of construction. This will include two manufacturing suites that are expected to come on-stream by mid-2011.
Lonza said additional suites could be added in the future to meet increased demand. This plant will be next to the company's existing large-scale mammalian production plant. The company already operates 12 cGMP-certified cell therapy manufacturing suites in the U.S. and Europe.
“Cell Therapy is expected to be one of the most important innovation drivers of modern medicine,” comments Stefan Borgas, Lonza CEO. “This new cell therapy manufacturing facility is the next step in fulfilling our strategy to expand our capacity globally and our presence in Asia. The expansion in Singapore further fortifies the strategic relationship Lonza has with the Singapore government, which has been developed through the successful build-up of our large-scale manufacturing facility.”
Source: GEN News Highlights, May 15, 2009

Orbital bioreactors set to shake up mammalian cell culture sector

ExcellGene's OrbShake 250L mammalian cell culture bioreactor has equalled biomass productivity and oxygenation levels previously only achieved by traditional stirred tank systems.
The bioreactor, launched early May at the Achema 2009 conference in Frankfurt, Germany, applies the orbital shaking mechanism used in prokaryotic culture systems to improve the mixing of mammalian cell suspension cultures.
The system features a cylindrical vessel containing a disposable, sterile bag with appropriate connection tubes for seeding, feeding, gas supply and harvesting which, ExcellGene claims, is simpler and less costly to operate than traditional bioreactors.
Orbital shaking generates higher mammalian cell culture biomass than stirred reactors without any loss in specific productivity. In addition, the ability to apply the same mixing principle from the ml to 1,000L reaction vessel size range will allow developers to model industrial scale-up more accurately than ever before.
Orbital shaking also provides significant cost savings over stirred tank systems in terms of energy costs, consumption of consumables. Swiss firm Kuhner and French biotechnology services provider Sartorius-Stedim will commercialise the orbital shaking technology.
Source: www.In-pharmatechnologist.com, May 13, 2009

Sanofi seeks collaborators for €200m biotech plant

French drug major Sanofi Aventis has unveiled plans for a €200m ($268m) biotechnology investment at its manufacturing facility in Vitry-sur-Seine near Paris, under its collaborative Biolaunch project. The investment will be used to install biotechnology manufacturing capacity at the plant which at present is used to produce Sanofi's oncology, cardiovascular, anti-infectives and anti-inflammatories some of which are due to go off-patent in the next few years.
The core focus of the Biolaunch project is to develop a cell culture platform, R&D and manufacturing centre which, when fully operational in 2012, Sanofi will use to develop and manufacture monoclonal antibodies (MAbs) and biologics. Sanofi CEO Christopher Viebacher said the project will create “a complete platform of expertise in biotechnologies,” adding that “monoclonal antibodies will open the way to a new generation of better targeted and more effective treatments with fewer side effects.” He added that Biolanuch is “an opportunity for the company to do partnerships with biotechnology and research companies," explaining that such “collaborations can provide us with new products." Biolaunch will also include a training program to help with new biotech business activities that comprises special modules for both theory and practice, with participants gaining a “Biolaunch passport” syllabus.
Earlier, Viebacher announced a major reorganisation of the firm's development pipeline that saw it cull 14 candidate drugs, including four that were in Phase III clinical trials. At the time he said that said that Sanofi will shift its focus away from traditional drugs and “aim to increase the percentage of biotech products in its pipeline from 14 to 25 per cent over the next three years.” Prior to that Sanofi demonstrated its commitment to expanding its biotechnology portfolio through the acquisition of California, US based cancer drug specialist BiPar for $500m.
Source: In-pharmatechnologist.com, May 5, 2009

GEA probe helps companies follow PAT initiatives

In-line and on-line monitoring forms part of the US Food and Drug Administration's (FDA) Process Analytical Technology (PAT) initiative but GEA believes current optical observations may be flawed. This is due to the risk of window fouling, an occurrence that can limit the user's view of the product and result in incorrect analysis data or unwanted interuptions of the process.
Consequently GEA and J&M Analytik AG designed the Lighthouse Probe to eliminate the risk of this occurring, using an array of cleaning processes and fibre optics. The technology can be used for processes involving wet and sticky powders, such as operations in fluid bed systems, high shear granulators or spray dryers.
GEA's Lighthouse Probe consists of five elements: a probe with optics; a spectrometer; software; movement unit and housing; and a clean-in-place (CIP) unit. To maintain visibility throughout monitoring the Lighthouse Probe uses in-process cleaning, ensuring a clear optical path during use, and CIP technology at the end of the operation. In addition the probe has a self-calibration facility that can check if the seven observation windows have become contaminated and if the spectrometer is properly configured. These features allow in-product measurement with 360° view and simultaneous use of various analytical methods, such as near infrared Raman (NIR).
Source: www.In-pharmatechnologist.com, April 29, 2009

SAFC and Vivalis launch high yield EB66 media

SAFC and Vivalis have launched a new media designed to allow the latter's commonly used virus producing EB66 cell line to grow at higher cell densities and produce higher yields. The Ex-Cell EBx media, which is animal component and serum free, has been optimized for EB66 and productivity without the need for microcarriers.
The EB66 line is derived from duck embryonic stem cells and is used for the commercial scale manufacture of prophylactic and therapeutic vaccines as well as recombinant proteins. The EB66 is licensed by Vivalis to 24 pharma and biotech companies for a range of applications. Firms using the technology include GlaxoSmithKline (GSK), Schering-Plough, CSL and Sanofi-Aventis.
SAFC, which will produce the media at facilities in both Europe and the US, is the sole manufacturer of the product and will work directly with biopharmaceutical and biotech companies that use the cell line on a contractual basis.
Source: www.In-pharmatechnologist.com, April 28, 2009

Millipore's deal to improve influenza vaccine purification

Millipore is collaborating with Microbix Biosystems to improve influenza vaccine manufacturing by developing a purification process using novel chromatographic technology. The aim is to create a single step process to replace ultracentrifugation, which the collaborators claim is expensive, complex and can create bottlenecks in process development during manufacturing scale-up. Millipore believes its novel chromatographic technology can improve the purification process and will develop this using egg-based influenza viruses supplied by Microbix. In addition Microbix will give Millipore access to its Virusmax technology.
Virusmax increases yield by harvesting the vaccine which is normally discarded after becoming attached to debris in the allantoic fluid of the chick embryo. Microbix claims the process is inexpensive to implement and does not create a serious regulatory barrier, owing to the non-toxic substances used in the technique.
Source: www.In-pharmatechnologist.com, April 27, 2009

Polestar launches sensor for disposable reactors

The rising popularity of disposable systems has created demand for new sensors, according to Polestar, because in-line monitoring and sampling for off-line analysis are both flawed when applied to single-use reactors.
In response to this demand Polestar has created the integrated Disposable Optical Transducer (iDOT), which it claims can monitor oxygen, pH and carbon dioxide without compromising sterility or risking breaking an electrode.
Manufacturers of bioprocess bags can add the sensors to their products by creating ports using the same technique for welding fluid inlets and outlets. The pre-calibrated sensor is then installed into the port and the whole system sterilised, with the iDOT able to stand this gamma irradiation.
Incorporating the iDOT into the reactor at this stage reduces the risk of contamination because there is no need to breach the bioprocess bag after sterilisation to add a sensor.
Polestar has designed the system to incorporate into the mass customisation business model, with reactor manufacturers able to incorporate the iDOT into clients bioprocess bags. The end user can then connect the sensor to a Polestar DSP Process Monitor using an optical cable.
Source: www.In-pharmatechnologist.com, April 20, 2009

Business News

Ernst & Young 2009 report: financial crisis could reshape biotech

Ernst & Young's global biotechnology report 2009, its 23rd annual look at the industry, said U.S. profit for the industry totaled $400 million. Despite the downturn, it’s not a “gloom and doom" situation for the sector, considering how necessary the many of the treatments are to a growing, and aging, population. In 2008, revenue at publicly traded biotech companies grew 12 percent to $89.7 billion in 2008, while the global industry's net loss improved to $1.4 billion from $3 billion, the report said.

Capital raised fell sharply, though, down 46 percent for the Americas and Europe combined to $16 billion. IPO funding all but disappeared, falling 95 percent to $116 million.

In the latest report, Ernst & Young said the characteristics of the current financial crisis make it a threat unlike any other for the industry. Public capital is constrained, which in turn means less companies that go public through initial public offerings, while there is lower value in buyouts and less debt financing available.
Without funding, the long and expensive process of testing new drugs isn't possible. Still, ongoing trends such as the expansion of personalized medicine, a wave of generic drugs and the continued globalization of the sector should usher in more sustainable ways of financing drug development, according to the report.
Many key blockbuster drugs will soon face generic competition, which could remove some pricing demand facing the broader drug industry. The introduction of generic drugs could allow for better margins on truly innovative products, putting a premium on biotech, the report says.
Source: The Associated Press, May 5, 2009

Genmab to sell manufacturing facility and cut 300 Jobs

Genmab is selling its manufacturing facility in Brooklyn Park, Minnesota, and has cut about 300 jobs worldwide as part of an approximately DKK 300 million (about $445.74 million) cost-cutting exercise. The overall projected savings will include non-cash items of approximately DKK 60 million, or about $89.16 million.
Genmab says that it will continue to focus on the development of antibody therapeutics for cancer and has no plans to drop any of its ongoing projects. As part of its drive to build what it describes as a more flexible model, however, the firm has decided to meet future manufacturing requirements through outsourcing. The Brooklyn Park facility, which is now ready for sale, will operate on a maintenance-only basis until a buyer has been found.
Genmab's announcement comes just a couple of weeks after the company and partner GlaxoSmithKline reported accelerated FDA approval of the fully human CD20 antibody, Arzerra™, as a treatment for patients with chronic lymphocytic leukemia (CLL) that is refractory to fludarabine and alemtuzumab. During August Genmab announced positive Phase II results of Arzerra as a front-line treatment in combination with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) in patients with previously untreated follicular non-Hodgkin's lymphoma (NHL).
Arzerra is being co-developed worldwide with GSK. The antibody is in various stages of clinical development for indications including CLL, NHL, rheumatoid arthritis, diffuse large B-cell lymphoma, relapsing remitting multiple sclerosis, and Waldenstrom's macroglobulinaemia.
Genmab's clinical pipeline also includes the EGF receptor antibody, Zalutumumab (HuMax-EGFr), which is being developed in house as a treatment for head and neck cancer either alone or in combination with radio/chemotherapy. RG1507 is a fully human antibody created by Genmab under a collaboration with Roche. The molecule targets the insulin-like growth factor-1 receptor and is in development as a treatment for sarcoma and a variety of solid tumors. Genmab's earlier-stage clinical pipeline includes antibody products discovered and developed either in-house or through its collaboration with Roche.
Source: GEN News highlights, Nov 5, 2009

Roche begins cutting jobs at Genentech

Swiss firm Roche has begun making cuts at recent $46.8bn biotech acquisition Genentech, in the first stage of a widely anticipated integration programme. The cuts, which will be carried out through a series of voluntary contract buyouts, would impact Genentech's late stage drug development and administrative units. Few if any jobs in Genentech's manufacturing and production operations will be lost, and activities at its distribution centers in Vacaville and South Francisco will continue to operate as normal.
The San Francisco Business Times reports that Roche will also halt manufacturing operations and cut jobs at its facility in Nutley, NJ.
In other news, Roche confirmed speculation that it plans to leave the US Pharmaceutical Research and Manufacturers Association (PhRMA) in favour of joining the Biotech Industry Organization (BIO).
The firm, which has also left the Association of the British Pharmaceutical Industry (ABPI), told the Star-Ledger that: "BIO’s purpose is closely aligned with the direction of the new company and … can represent the company’s interest in Washington."
Source: In-pharmatechnologist.com, July 13, 2009

Novartis to invest $1.25B in two new facilities in China

Novartis is to plough $1 billion into the construction of a new Novartis Institute for BioMedical Research in Shanghai (CNIBR) and another $250 million into a global technical center for APIs in Changshu, China. 
The five-year Chinese investment plan will involve moving and expanding Novartis' existing CNIBR, which is situated in Zhangjiang High-tech Park, to a new campus in Shanghai. Once completed, the new facility is expected to be Novartis' third largest R&D center worldwide, behind its facility in Cambridge, MA, and headquarters in Basel, Switzerland.
Activities at the new CNIBR will span analytics and biomarkers, in vivo pharmacology, protein production, characterization and scale-up screening, chemistry and proteomics, along with genomics and imaging.  The facility will employ an estimated 1,000 R&D staff compared with the 160 R&D associates at the current CNIBR site.
The $250 million investment in a new global technical center for APIs in Changshu, meanwhile, will be used to establish complementary activities focused on technical R&D and manufacturing. By locating both activities at a single site, Novartis hopes to enhance API process development and operational efficiency.
Source: GEN News highlights, Nov 3 2009

Novozymes begins work on Chinese bHA plant

Novozymes Biopharma is building a new Bacillus-based hyaluronic acid (bHA) production facility in China to meet “increasing demand” for the substance that has drug delivery applications. The facility is being built at Novozymes’ existing site in Tianjin in eastern China, which Novozymes says may become a cluster housing plants producing bulk active pharmaceuticals and other ingredients for the industry. Preparatory steps for these potential expansions are incorporated into the current $35-50m construction, which when complete in Q1 2011 will provide pharmaceutical grade (Q7) bHA to the industry.
bHA has been traditionally derived from rooster combs or strains of streptococcal bacteria but these methods are known to be pathogenic. Consequently Novozymes has developed an animal-free bHA using non-pathogenic fermentation method, which produces a high quality product without using organic solvents, according to the company.
The bHA produced ay the site will go towards meeting rising demand for the substance, which is widely used in medical device applications and in research into drug delivery methods, including anticancer therapeutics, tissue engineering, and bone regeneration treatments.
Source: www.In-pharmatechnologist.com, April 28, 2009

Hovione shows off Irish API plant

API maker Hovione's manufacturing facility in Cork, Ireland was unveiled at an opening ceremony yesterday just two weeks after the previous owner, global drug giant Pfizer, formally handed over the keys.
The plant can handle a large number of specialised operations such as hydrogenation and low temperature chemistry, and boasts a new, €70m ($91m) spray-dried formulations unit. Under Pfizer the facility's main focus was the production of the active ingredient for the firm's biggest seller, the world leading hypertension blockbuster Lipitor (atorvastatin). Hovione said it will continue to make some active pharmaceutical ingredients (API) on Pfizer's behalf, but stressed the production of its roster of drug actives as well as contract manufacture will be the main focus of activities at the site.
Over the last few years Hovione has increased API manufacturing capacity by around 50 per cent in response to the rising demand for outsourced manufacture that currently dominates the drug industry.
Source: www.In-pharmatechnologist.com, April 23, 2009

Vaccine News

HIV vaccine cuts infection by 31.2% in 16,000 Thai trial

A six-year Phase III trial involving more than 16,000 adult volunteers in Thailand has demonstrated that a vaccine combining Sanofi Pasteur's ALVAC vaccine and AIDSVAX, developed by VaxGen and now owned by the Global Solutions for Infectious Diseases, was “safe and modestly effective” in preventing HIV infection. According to the trial sponsor, the US Army Surgeon General, the prime boost combination of the two treatments lowered the rate of HIV infection by 31.2% compared with placebo.

In the analysis, 74 placebo recipients became infected with HIV compared to 51 in the vaccine regimen arm, a statistically significant result. The combo had no effect on the amount of virus in the blood of volunteers who became HIV-infected during the study, more details from which were presented at the AIDS Vaccine Conference (October 19-22) in Paris.

This is the first HIV vaccine candidate to successfully reduce the risk of infection in humans. Michel DeWilde, R&D senior vice president for Sanofi Pasteur, noted that “albeit modest, the reduction of risk of HIV infection is statistically significant” and “this is the first concrete evidence, since the discovery of the virus in 1983, that a vaccine against HIV is eventually feasible”. He added that “further work is required to develop and test a vaccine suitable for licensure and worldwide use,”
Source: PharmaTimes.com, September 24, 2009

Sanofi invests €350m in dengue fever facility

Sanofi-aventis is has made its largest ever investment in its vaccine capacity, using €350m ($479m) to construct a dengue fever vaccine manufacturing plant in France. The facility is being constructed in Neuville-sur-Saone, near Sanofi Pasteur’s headquarters in Lyon, France. Sanofi is currently constructing or renovating 12 manufacturing facilities.
Vaccines have been identified by Sanofi, and several other pharmas, as a growth area in the coming years, with the prevalence of dengue fever meaning there will be a sizeable market for a treatment. Sanofi is still developing the vaccine, which is currently in clinical trials, with regulatory submission possibly being sought in 2012. This would be a year before the vaccine plant is predicted to be operational, when it will begin producing 100m doses a year. Successful development and regulatory approval of Sanofi's dengue fever vaccine will provide a treatment for an increasingly large number of patients that are being affected as the disease spreads. The World Health Organization (WHO) has stated that “the incidence of dengue has grown dramatically around the world in recent decades”, with 2.5bn people now at risk.
Source: www.In-pharmatechnologist.com, May 13, 2009

Novartis to buy 85% of Chinese Vaccines Company for $125M

Novartis has negotiated a $125 million cash deal to purchase 85% of Chinese vaccines company Zhejiang Tianyuan BioPharmaceuticals. The announcement comes just 24 hours after Novartis confirmed plans for a five-year, $1.25 billion investment plan in China, involving the construction of a new Novartis Institute for BioMedical Research in Shanghai and a global technical center for APIs in Changshu (see article below). 
The proposed acquisition of Tianyuan will see Novartis working with the company to expand its product portfolio and R&D pipeline. Novartis says that the partnership is also expected to facilitate the introduction of Novartis vaccines into China, where it currently has limited exposure. Novartis’ vaccine offerings in China currently only comprise influenza and rabies products.
Tianyuan is a privately owned company with a range of marketed vaccine products in China, including seasonal influenza, hemorrhagic fever with renal syndrome, Japanese encephalitis, and meningococcal meningitis. The company's DTaP (diphtheria, tetanus, and pertussis), meningococcal Men PS A, and typhoid Vi PS vaccines are currently progressing through regulatory submission. Earlier-stage products in development include a pandemic H5N1 flu vaccine, a pneumococcal polyscaccharide vaccine, a hemophilus influenza type B vaccine, and a meningococcal A/C conjugate vaccine. Tianyuan's net sales doubled in the 2006–2008 period to $25 million.
China is believed to represent the world's third-largest vaccines market, with annual industry sales of over $1 billion and expected double-digit growth as a result of governmental plans to improve access to healthcare for the whole population.
Source: GEN News highlights Nov 4, 2009

Collaborations, mergers and acquisitions

GSK and Pfizer launch HIV joint venture

GlaxoSmithKline and Pfizer have launched a specialist HIV company with access to ten medicines developed by the two manufacturers. ViiV Healthcare, headquartered in London and North Carolina, will also have a right of first negotiation on any new HIV-related medicine developed by either company. As well as looking at new medicines, ViiV’s R&D programme will attempt to create new formulations and combinations to resist the virus.
GSK holds an 85% interest in ViiV to Pfizer’s 15% and, like Limet, the majority of the new company's senior management team are former GSK staffers. The new company's portfolio of established antiretrovirals generated sales of £1.6 billion last year, cash that will be used by ViiV to invest in its pipeline. This currently contains seven medicines and includes five compounds in phase II development. Half of ViiV’s existing drugs are nucleoside reverse transcriptase inhibitors (NRTIs): Combivir, Epivir/3TC, Epzicom/Kivexa, Retrovir/AZT, Trizivir and Ziagen. GSK's newer medicine Epzicom/Kivexa, which has seen sales growth this year, will be expected to perform well alongside its older combinations, such as Combivir and Trizivir. In addition, ViiV has Rescriptor, a non-nucleoside reverse transcriptase inhibitor (NNRTI) available only in the US; originally a Pharmacia product, it was swallowed by Pfizer in those companies’ merger several years ago. There are also two protease inhibitors (PIs), which prevent the production of mature, infectious virus particles in infected human cells by blocking the protease enzyme. These are Lexiva/Telzir which, when GSK launched it in the UK in 2004 was the first PI to have no food or drink restrictions for patients. And Viracept, available in North America only, was launched by Pfizer a decade ago. Finally, ViiV has one CCR5 antagonist: Selzentry/Celsentri, a Pfizer drug approved in Europe in 2007.
Source: Pharmafocus, November 11, 2009

GSK forms joint venture to expand in Chinese vaccine market

GSK and Walvax have entered into a long-term joint venture to serve the Chinese vaccine market, with the big pharma transferring technology to enable local production and building a manufacturing plant. The joint venture strengthens GlaxoSmithKline’s (GSK) position in two growth areas, China and vaccines, and is in keeping with the pharma's recent strategy. GSK has signed a similar deal with China-based Shenzhen Neptunus Interlong Bio-Technique to develop and manufacture flu vaccines. By making these deals GSK Biologicals can establish a presence in China “in advance of the significant expansion in the Chinese public vaccine market”.
In 2008 the Chinese Ministry of Health's incorporated the measles, mumps and rubella (MMR) vaccine into its immunisation programme following its pledge to eradicate measles by 2012. GSK is anticipating that this will drive growth in the Chinese vaccine market.
Under the terms of the deal with Walvax the partners will invest £41.2m ($65.5m) in the joint venture upon fulfilment of certain conditions. This investment includes an initial £20.1m from GSK, and further £7.3m by 2015, and a total of £13.8m from Walvax. Some of this investment will be used to build a manufacturing facility for GSK's paediatric MMR vaccine Priorix. Once the facility is complete it will supply vaccines to the Chinese market.
The partners are also working to develop and manufacture paediatric vaccines for the Chinese market. GSK is transferring technology to allow the joint venture to manufacture vaccines locally.
Source: In-pharmatechnologist.com, October 7, 2009

Novartis to Buy EBEWE Pharma's Generics Business for $1.2B

Novartis  is paying $1.2 billion in cash for Austria-based EBEWE Pharma's specialty generic injectables business. The deal includes EBEWE Pharma's portfolio of oncology and immunology products, Austrian manufacturing site, and IP, but excludes EBEWE’s separate injectable neurological products business.
Novartis said the acquisition will give its own generics business, Sandoz, a major new portfolio of oncology drugs and the opportunity to establish a new global center of excellence at the EBEWE site in Austria, led by the latter's current CEO, Friedrich Hillebr. The new center aims to capitalize on EBEWE Pharma's hospital marketing expertise and customer partnerships, along with skills in developing differentiated generics and injectables manufacturing.
A subsidiary of BASF for nearly 50 years, EBEWE Pharma became independent following a management buyout in 2001. The company is focused on developing innovative generics, including ready-to-use liquid formulations, new dosage forms, advanced delivery devices and new packaging. Net sales of $272 million were recorded in fiscal 2008, and 20% compound annual sales growth achieved since 2006. Among the company’s generics portfolio are front-line treatments including paclitaxel, epirubicin, methotrexate, oxaliplatin, carboplatin, doxorubicin, and gemcitabine.
Source: GEN News highlights, May 20, 2009

BioInvent teams up with Mitsubishi Tanabe Pharma Corporation for therapeutic antibodies

BioInvent International AB has signed a license agreement with Mitsubishi Tanabe Pharma Corporation for the development of antibodies, up to five therapeutic targets, from BioInvent’s n-CoDeR® library. Under the terms of the agreement, Mitsubishi Tanabe will be granted access to BioInvent's discovery and development technology platform.
BioInvent will receive an undisclosed upfront access fee, annual maintenance fees as well as royalties on commercialised products and success-based milestone payments. The agreement follows on an existing research license and a feasibility study concluded earlier this year.
The n-CoDeR® library contains more than 20 billion (2 x 1010) highly diverse, fully human antibody fragments that have been created using BioInvent's patented approach, generating antibodies with high affinity and selectivity.
Source: BioInvent Press Release, July 31, 2009

Biovitrum to acquire Swedish Orphan for Over $500M

Biovitrum is purchasing Swedish Orphan for SEK 3.5 billion (about $501.59 million) up front on a cash- and debt-free basis. With a combined product portfolio of some 60 orphan/niche specialty products, the new entity aims to achieve sales of over SEK 5 billion (roughly $716.30 million ) in 2015. The acquisition of Swedish Orphan comes less than a week after Biovitrum confirmed selling its wholly owned drug discovery subsidiary, Cambridge Biotechnology (CBT), and a number of its own drug development programs to Proximagen Neuroscience.
With sales in over 50 countries worldwide, Swedish Orphan’s European presence includes 11 subsidiaries and six branch offices covering all areas in Europe. The company achieved sales in fiscal 2008/09 of SEK 694 million (about $99.34 million). Biovitrum has eight marketed products along with one candidate in Phase III and another five in Phase II. In October Biovitrum and its partner Biogen Idec confirmed plans to advance the long-acting, fully recombinant Factor IX Fc fusion protein (rFIXFc) into a registrational trial in hemophilia B patients.
Biovtrum also generates revenues from the manufacture of protein therapeutics for clinical and commercial supply and is the sole global manufacturer of the active protein substance in Wyeth’s hemophilia A drugs, ReFacto® and ReFacto AF®/Xyntha®. In December 2008, the companies extended their manufacturing agreement to the end of 2015.
Source: GEN News highlights, Nov 5, 2009

Abbott to take over Solvay for roughly $6.6B

Abbott Laboratories is picking up Solvay Pharmaceuticals for €4.5 billion, or about $6.6 billion, in cash. The deal gives Abbott entrance into the vaccines market, a complementary portfolio of therapeutics, and a stronghold in certain emerging markets. It also includes full global rights to the Tricor (fenofibrate) franchise; currently Abbott has U.S. rights to Tricor and pays royalties to Solvay. The drug is indicated to manage cholesterol. Belgium-based Solvay Pharmaceuticals is expected to add over $3 billion in annual sales, the majority of which will come from outside the U.S. Solvay has built an infrastructure in emerging markets in Eastern Europe and Asia.
The acquisition will also add approximately $500 million to Abbott’s annual pharmaceutical R&D investment. Solvay also has a molecular diagnostics unit, which will become part of Abbott’s diagnostics organization. Solvay has treatments for hypertension, Parkinson’s disease, Ménière's disease, vertigo, and irritable bowel syndrome. Solvay also offers products to treat men's and women’s hormonal health and exocrine pancreatic insufficiency.
Source: GEN News Highlights, September 28, 2009

Research News

Cell on a Chip

The first artificial cell organelle may help researchers find a way to make bioengineered heparin and other synthetic drugs. The drug heparin is widely used to prevent blood from clotting in medical procedures ranging from dialysis to open-heart surgery.  But its widespread use belies its crude origins: more than 90 years after it was discovered, heparin is still made from pig intestines. But a new microfluidics chip, which mimics the actions of one of the cell’s most mysterious organs, may help change that. Researchers at Rensselaer Polytechnic Institute in Troy, NY, have created the first artificial cellular organelle and are using it to better understand how the human body makes heparin. The artificial cell organelle is a small microfluidics chip that mimics some of the Golgi’s actions. The digital device allows the researchers to control the movement of a single microscopic droplet while they add enzymes and sugars, split droplets apart, and slowly build a molecule chain like heparin. By testing reagents in different amounts, with different reaction times, the artificial Golgi may be able to teach them how to synthesize heparin and other molecules in a laboratory setting.
Source: MIT Technology Review, August 11, 2009

Stem cell news

Pfizer's stem cell unit and UCL focus on eye disorders

Pfizer’s development deal with stem-cell researchers at University College of London’s (UCL) Institute of Opthalmology, aimed at reversing vision loss in AMD, has drawn a great deal of interest from investors and the drug industry alike. The research team, which is lead by Professor Pete Coffey, hopes to develop a regenerative therapy that can replace the eye tissue due to age related macular degeneration (AMD). The group has found a way of converting embryonic stem cells into retinal pigmented epithelial (RPE) which, when, transplanted into animals, replace those lost by the disease. Now that the Pfizer deal has gone through the team expect to begin clinical trials in 2010 or 2011.
An early indication of Pfizer’s interest in stem cell based therapies came in November when, in contrast with its efforts to trim R&D spending in other areas of its business, the firm set up its 70-strong regenerative medicine research unit at sites in the US and UK. One of the earliest beneficiaries of Pfizer’s deal with the UCL is UK regenerative medicine firm Intercytex, whose share price leapt 68 per cent to £9.88 when the news broke late last week. The Cambridgeshire firm’s subsidiary Axordia, which it bought in December, provides UCL with the SHEF-1 embryonic stem cells that are used to recreate the RPE cells that form the basis of the technology.
Source: In-Pharmatechnologist.com, May 5, 2009

Awards

Three US scientists share Nobel Prize for telomere research

Until now, replicating cellular DNA without damage to chromosomes has been problematic. However, the work of the trio of US-based scientists Elizabeth H. Blackburn, Carol W. Greider and Jack W. Szostak has brought new hope by revealing the unique DNA sequence in the telomere that protects the chromosome during this process. For that they received jointly one of this year’s Nobel Prizes.
These discoveries have had a major impact within the scientific community at large as, for some time, scientists had speculated that telomere shortening could be the reason for ageing of cells and organisms.
Since most normal cells do not divide frequently their chromosomes are not at risk of shortening and they do not require high telomerase activity. However, in contrast, cancer cells have the ability to divide infinitely and yet preserve their telomeres. Further studies can now be undertaken to establish the significance of this gene sequence and enzyme in the replication of malignant and healthy cells. Several studies are already underway in this area, including clinical trials evaluating vaccines directed against cells with elevated telomerase activity.
“This award represents the achievement of a lifetime for any scientist” commented Willy de Greef, Secretary General for EuropaBio, “However, for most, it also represents a lifetime’s work. This year’s winners began their initial research several decades ago in the mid 1980s. In the EU we are often far less ready than our competitors to acknowledge that achievements such as these take not only academic brilliance but also vast amounts of financial and human resources. That needs to change if we are to make the most of our own homegrown talent in working towards finding EU healthcare solutions to global healthcare problems”
Source: EuropaBio Press Release

Alternative methods to reduce the use of animals in research rewarded

Roche announced the winners of its global 3Rs Award Program - a unique and innovative program that helps to reduce and limit the use of animals in preclinical research - to recognise and reward innovation and continuous improvement in animal welfare within the Roche research organisation. The award, which is now in its second year, is based on the 3Rs concept, which means Replacing animal tests where possible, Reducing the number of animals required and Refining existing scientific practices as well as animal care and husbandry. Fifteen teams of Roche scientists and animal care specialists from the companies’ global research sites in Basel, Penzberg, Nutley and Tokyo applied for awards in two categories: “Scientific Progress Fostering the 3Rs Idea” and “Laboratory Animal Care and Management”.
Source: Roche Group Media Relations, September 24, 2009

AGENDA

ACTIP meeting
November 19-20, Leiden, The Netherlands
Only for ACTIP members
Info: actip-secretariat@telefonica.net

BIOTECH Expo
24-27 November, Milan, Italy

Vaccine Research & Development 2009
Moving from technology to manufacturing and production
7th - 8th December 2009, BSG House, London, UK
jana.jankova@vgpharma.com

Cell Line Development and Engineering
1 – 5 March 2010, Prague, Czech Republic
www.informa-ls.com/celldev

March 3-5, 2010
EMBL Workshop on Visualizing Biological Data (VizBi), Heidelberg, Germany

March 8-10, 2010
Bio-Europe Spring Barcelona, Spain

Cell Culture Engineering XII
April 25-30, 2010, Banff, Alberta, Canada
Information: info@engconfintl.org 

May 2-4, 2010
ERBI's 12th Annual BioPartnering Exchange, Cambridge, UK

May 26-28, 2010
20th Anniversary World Congress on Biosensors, Glasgow, UK

Sept 30-Oct 2, 2010
BIOSPAIN, Pamplona, Spain