Stephanie Sutton was an assistant editor at Pharmaceutical Technology Europe.

Stephanie Sutton

GlaxoSmithKline (GSK) has entered into an agreement to purchase Shenzhen Neptunus’ stake in a previously formed joint venture between the companies involved in the development and manufacture of influenza vaccines in China, Hong Kong, and Macau. GSK will pay Shenzhen Neptunus $39 million, after which GSK will be the sole owner of the joint venture company, Shenzhen GSK-Neptunus Biologicals (GSKNB).

GSKNB was established by GSK and Shenzhen Neptunus in June 2009, to develop and manufacture seasonal and pandemic influenza vaccines. The joint venture combined GSK’s adjuvant technology and expertise in vaccine development with Shenzhen Neptunus’ experience in the Chinese market. Under the terms of the original agreement, GSK was expected to purchase additional shares and obtain a majority equity interest in the company within two years. Subsequently, in August 2010, GSK increased its equity share in the joint company from 40% to 49%.

 from GSK, the decision to acquire all the outstanding interest in GSKNB reflects the company’s intention to further expand its vaccines presence in China, which it describes as a “fast growing emerging market.”

“GSK has licensed more vaccines in China than any other global manufacturer and has packaged more than 100 million vaccines at our Shanghai facility,” claimed John Lepore, vice-president and general manager of biologicals and corporate at GSK China, in the statement. “This announcement represents an expansion of GSK’s long-term commitment to vaccine supply, manufacturing and development in China.”

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GlaxoSmithKline has entered into an agreement to purchase Shenzhen Neptunus? stake in a previously formed joint venture between the companies involved in the development and manufacture of influenza vaccines in China, Hong Kong, and Macau.

GSK Expands its Vaccine Presence in China

Believing that transparency in the pricing of medicines is “fundamental” to enabling patients and stakeholders to make proper decisions about equity and value for money in health systems, the European Public Health Alliance (EPHA) called for greater pricing transparency. EPHA also called for the formation of a public website that provides comparative information on medicines’ procurement prices. EPHA’s calls are a response to the European Commission’s consultation on the possible revision of Directive 89/105/EEC, which concerns the transparency of the pricing and reimbursement of medicines in various member states.

“The primary concern of EPHA is examining the effect of pricing transparency on the end user, that is to say the consumer of medicines. All patients are entitled to have timely access to high-quality, efficient, safe, essential medicines. No patient should be prohibited from accessing such medicines due to costs,” explained a 

EPHA believes that the consultation should examine how transparency in medicines' pricing would place National Competent Authorities in a stronger position for negotiating prices when procuring medicines. In its statement, EPHA said: “Prices are often intransparent, as seen during the H1N1 pandemic in 2009, in which some Member States had had secrecy clauses written into their contracts for the procurement of the vaccine, meaning that others, lacking full information, were unable to negotiate effectively for a fair price.”

Another concern of EPHA is the timely availability of medicines. The alliance emphasizes that the time periods for pricing and reimbursement decisions laid down in the Directive should be adhered to.

“There is substantial evidence that in some [European Union] countries, pricing and reimbursement decisions are subject to unjustifiable delays, and in some countries there is an absence of effective sanctions. While we [recognize] there are obstacles to imposing sanctions through the Directive itself, the Directive can require Member States to ensure that effective remedies are available to affected parties (including patients) for breaches of the time limits,” said EPHA.

As a possible means of ensuring pricing transparency, EPHA cites a publicly accessible, regional database established by the World Health Organization that encourages the exchange of price information. “The Transparency Directive could establish such a website to provide comparative information on procurement prices for all medicines purchased by Member States. Such a database would also facilitate more rapid pricing decisions in those countries which operate external reference pricing schemes,” said EPHA.

The European Public Health Alliance has called for greater pricing transparency, as well as the formation of a public website that provides comparative information on medicines' procurement prices.

Alliance Calls for European Pricing Transparency

Medicines are often prescribed to children even though they have only been designed and tested in adults because of the ethical and practical issues associated with conducting pediatric trials. However, children's drug kinetics, metabolism, and dynamics can vary substantially compared with adults, which is why a consortium in Europe is exploring the potential of microdosing to obtain pharmacokinetic data that could be used to study new drugs. In particular, the consortium will be looking to improve drug development for infants (children aged 0–2 years) by using accelerator mass spectroscopy to overcome the main microdosing issue of measuring extremely low concentrations of drug candidates in tiny blood samples.  

I found out more about this project during an interview with Wouter Vaes, who is responsible for early clinical development at the TNO in The Netherlands, one of the institutes involved in the consortium. 

"Microdosing is one of the best tools that industry can choose to obtain human data at early stage in development," said Vaes. "Eventually, we expect that microdosing will be used to derive kinetic and metabolic information for all age groups at the same time." 

If successful, the project could encourage greater uptake of microdosing. Microdosing provides data about a drug's pharmacokinetics and pharmacodynamics in humans at an early stage of development. With the potential to be a valuable drug development tool, microdosing is definitely a technology to keep an eye on. 

Can microdosing make medicines safer and more effective for children?

The Pediatric Challenge

The pharmaceutical industry has been called to action by a new report that highlights the health and cost repercussions of patient noncompliance. According to Capgemini’s report, 

Patient Adherence: The Next Frontier in Patient Care

patient adherence to medications for chronic conditions, such as HIV and Arthritis, averages at only 50%.

“[A]lmost all chronic conditions face high rates of nonadherence and those with no visible symptoms, such as depression, have the lowest adherence rates. The problem even extends to oral formulation chemotherapy drugs, where one would not expect to encounter patient adherence issues due to the seriousness of the condition. As much as 40% of cancer patients are nonadherent in this case,” says the report.

The report estimates that patient nonadherence to prescribed medicine courses is responsible for 194,500 deaths per year in the European Union (EU) and 131,400 deaths per year in the United States. Nonadherence results in annual costs of close to EUR 125 billion in the EU and $300 billion in the US, according to the report.

The report makes several recommendations to improve patient adherence. However, the report also explains that it is a difficult issue to tackle, even with patient-adherence programs.

“Patient adherence is difficult to address because each situation is specific, based on patient behaviors, or the condition he or she is being treated for,” says the report. “The healthcare system does not have aligned incentives for all stakeholders to monitor and improve treatment adherence. Poor understanding of patient needs and behaviors, insufficient prioritization or siloed approaches can hold back programs helping patients undergo complete, on-time, and at-prescribed-dosage courses of medication.”

One of the recommendations is for the healthcare industry to take advantage of new digital health media tools, such as digitalized patient records and information sharing through the Internet, which will enable healthcare stakeholders to manage information effectively, identify points where adherence ceases, and help create programs to address them.

The pharmaceutical industry has also been urged to take action. The report suggests considering patient adherence early in development as a strategic issue that is part of the product-value proposition.

“The pharmaceutical industry needs to address patient adherence in a more strategic and integrated part of its activities, which will be good for the patients and for the industry overall,” Jean-Marc Neimetz, global leader of the life-sciences practice at Capgemini Consulting, said in a 

Thomas Forissier, a principal of the life-sciences practice, Capgemini Consulting, added, “Pharmaceutical companies need to design and deploy programs targeted to the very specific patient situations and leverage both traditional and digital approaches to do so.”

The pharmaceutical industry has been called to action by a new report that highlights the health and cost repercussions of patient noncompliance.

Capgemini: Pharma Must Act Against Patient Noncompliance

Following recent accusations that the European Medicines Agency (EMA) puts companies’ commercial interests ahead of public safety, EMA has 

 by emphasizing recent agency initiatives at the agency to improve data access.

Opening up data at the European Medicines Agency

," which described efforts by the authors to obtain access to unpublished trial reports at the EMA concerning the antiobesity drugs, rimonabant and orlistat. The authors first requested access on June 29, 2007, but did not receive the data until Feb. 1, 2011, after intervention by the European Ombudsman. In particular, the authors claim that the regulator was protecting drug company profits above patient welfare by withholding access to the data. In a 

 released in 2010, the European Ombudsman also accused EMA of maladministration for not granting access to the reports.

Protection of commercial interests was the EMA’s over-riding argument," explained the article. "It would undermine the protection of commercial interests to allow us access, it said, as the documents represented the full details of the clinical development programme and the most substantial part of the applicant’s investment."

The authors argued, however, that the clinical study reports and protocols are based on well-known principles that can be applied to any drug trial. They also explained the consequences of selective reporting.

"Comparisons of published drug trials with unpublished data available at drug regulatory agencies have shown that the benefits of drugs have been much over-rated and the harms under-rated. Comparisons of trial protocols with published papers have also shown widespread selective reporting of favourable results," claims the article.

In response, EMA has outlined moves it has made to increase access to data and transparency.

"The authors make what appears to be a compelling call for more transparency by the regulatory authorities," said EMA in a 

 to the BMJ. "However, they do so by ignoring the steps taken by the European Medicines Agency since it was established in 1995 and the latest actions and policy adopted over the last few years."

In November 2010, EMA implemented a new access to documents policy, which the agency claims has "pushed transparency further forward than in most other drug regulatory authorities." EMA also added that the extended access to documents and reactive disclosure of documents will be complemented by an "extended proactive publication" of these documents over the next few years.

Additionally, EMA drew attention to its recently launched EU Clinical Trials Register, which will enable patients and doctors to find information about clinical trials taking place in Europe.

"Further developments of this system are planned in the future, including publication of summaries of clinical trial results," said the EMA.

"Our case sets an important precedent," said the BMJ article. "On 30 November 2010 the EMA declared it would widen public access to documents, including trial reports and protocols. We recommend that the FDA and other drug regulatory agencies should follow suit. Access should be prompt—for example, within three months of the regulator’s decision—and documents should be provided in a useful format."

Following recent accusations that the EMA puts companies' commercial interests ahead of public safety, the EMA has responded by emphasizing recent initiatives at the agency to improve data access.

EMA Responds to Transparency Criticism

Amylin Pharmaceuticals has filed a lawsuit against Eli Lilly, alleging that Lilly is engaging in "anticompetitive activity" and "breaching its strategic alliance agreements with Amylin to maximize commercialization of exenatide." According to Amylin, Lilly is planning to jointly develop and commercialize a linagliptin product with Boehringer Ingelheim that will directly compete with Amylin’s exenatide products.

Exenatide is a first-line treatment for Type II diabetes that Amylin and Eli Lilly companies developed and commercialized together as an injection under the brand name Byetta after entering into an alliance in 2002. The companies are also in the process of gaining approval for Bydureon, an extended-release formula of exenatide. Bydureon received a positive opinion from EMA’s Committee for Medicinal Products for Human Use in April this year, but it was rejected by FDA in 2010.

“The principle relief Amylin seeks is to prevent Lilly from proceeding with its plans to use the same sales force to sell both exenatide and Boehringer Ingelheim’s competitive linagliptin,” said a

 from Amylin. “Amylin selected Lilly as a partner to promote development and maximize sales of Amylin's exenatide products. We are disappointed that we could not resolve this matter amicably and that we were forced to bring legal action to protect our rights, our products and our shareholders.”

 its strategic alliance with Boehringer Ingelheim in January. In a statement, the companies said they were intending, among other projects, to jointly develop and commercialize a pipeline of oral diabetes agents and basal insulin analogues.

 to Amylin’s allegation, Eli Lilly strongly denies any wrongdoing. “We believe the lawsuit is without merit and will vigorously defend our position,” Enrique Conterno, president of Lilly Diabetes, said in a statement. “Lilly has been and remains fully committed to fulfilling its obligations under its exenatide collaboration agreement with Amylin, as well as to complying with all laws and regulations.”

Eli Lilly added that it has devoted significant talent, resources, and know-how to the Eli Lilly–Amylin collaboration, and that the companies are planning to submit a reply to FDA’s complete response letter in the second half of 2011.

In its own statement, Amylin also emphasised that it will continue to collaborate with Eli Lilly in the development and commercialization of exenatide products.

Amylin Pharmaceuticals has filed a lawsuit against Eli Lilly, alleging that Lilly is engaging in anticompetitive activity and breaching its agreements with Amylin to maximize commercialization of the drug, exenatide.