Kidneys and Livers, Made to Order?

By Seán Finan

Last week, Organovo might just have revolutionised the pharmaceutical industry. The San Diego-based company specialises in producing structures that mimic the behaviours and functions of human tissue, using 3D bioprinting. They announced last week that they were beginning the commercial manufacture and sale of their ExVive Kidney. The product models the proximal tubule of the human kidney and holds significant promise for clinical trials of new drugs. The commercialization of the ExVive Kidney follows the release of ExVive Human Liver Tissue in 2014.

In essence, Organovo is using 3D printing technology to produce samples of “human” tissue that can be used to test the toxicity of new drugs. The printing process, known as 3D bioprinting, involves extracting human cells, culturing them and suspending them in a solution. The resulting “bioink” is fed through a modified 3D printer. Layer by layer, the printer deposits cells, producing a mass with a similar structure and density to a sample of, for example, human liver. Just like “organ on a chip” technology, these synthetic liver and kidney samples present significant advantages over traditional clinical testing.

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European Responses to the Ebola Crisis: Initiatives at the European Medicines Agency (EMA)

By Timo Minssen

The current Ebola outbreak already attracted much attention on “Bill of Health” resulting in some excellent blogs on a horrible topic.

While it is evident that the current health crisis requires both immediate responses and more sustainable changes in health care policy, research and regulation, medicines regulators are collaborating internationally to find innovative solutions enhancing evaluation of and access to potential new medicines to fight Ebola outbreaks. In a statement announced by the International Coalition of Medicines Regulatory Authorities (ICMRA) in September 2014, regulators around the world led by the FDA and the EMA have vowed to collaborate in supporting accelerated evaluation of experimental new drugs to treat Ebola virus infections and say they will encourage submission of regulatory dossiers. This clearly backs up the World Health Organization’s (WHO) decision to test experimental Ebola treatments in infected patients in the current outbreak region in West Africa and to speed up the development of vaccines.

In the following I would like to summarize and discuss some of the recent European responses to the current crisis starting with an overview on recent initiatives at the EMA.

Like its US counterpart, the EMA leads a close and consistent dialogue with public and private developers of Ebola products and spends much effort in reviewing available information on the various experimental Ebola treatments currently under development. These experimental drugs range from experimental antivirals or vaccines based on the adenovirus or stomatitis vaccine to experimental therapies based on mono- and polyclonal antibody technologies. One of these unapproved antibody combination drugs – MAPP Biologicals’  ZMapp – has already been used in some care workers affected by Ebola. Other experimental drugs that are currently reviewed by the EMA include Biocryst’s BCX 4430, Fab’entech’s Hyperimmune horse sera, Sarepta’s AVI-7537, Toyama Chemicals and MediVector’s Favipiravir and Tekmira’s TKM-Ebola.

Other companies such as Bavarian Nordic  and the Russian Mikrogen are close to follow.

In addition to monitoring experimental drugs and enhancing global collaboration, the European Medicines Agency has like the FDA initiated several activities in order to support and speed up the development of these drugs towards market approval.  Continue reading

Bumps on the Road Towards Clinical Trials Data Transparency- A recent U-Turn by the EMA?

By Timo Minssen

In a recent blog I discussed the benefits and potential draw-backs of a new “EU Regulation on clinical trials on medicinal products for human use,” which had been adopted by the European Parliament and Council in April 2014. Parallel to these legislative developments, the drug industry has responded with its own initiatives providing for varying degrees of transparency. But also medical authorities have been very active in developing their transparency policies.

In the US, the FDA proposed new rules which would require disclosure of masked and de-identified patient-level data. In the EU, the EMA organized during 2013 a series of meetings with its five advisory committees to devise a draft policy for proactive publication of and access to clinical-trial data. In June 2013 this process resulted in the publication, of a draft policy document titled “Publication and access to clinical-trial data” (EMA/240810/2013).

Following an invitation for public comments on this document, the EMA received more than 1,000 submissions from stakeholders. Based on these comments the EMA recently proposed “Terms of Use” (TOU) and “Redaction Principles” for clinical trial data disclosure.

In a letter to the EMA’s executive director Dr. Guido Rasi, dated 13 May 2014, the European Ombudsman, Emily O’Reilly, has now expressed concern about what seems to be a substantial shift of policy regarding clinical trial data transparency. Continue reading

A More Transparent System for Clinical Trials Data in Europe – Mind the Gaps!

By Timo Minssen

Following the approval of the European Parliament (EP) earlier last month, the Council of the European Union (the Council) adopted on 14 April 2014 a “Regulation on clinical trials on medicinal products for human use” repealing Directive 2001/20/EC.  As described in a press-release, the new law:

“aims to remedy the shortcomings of the existing Clinical Trials Directive by setting up a uniform framework for the authorization of clinical trials by all the member states concerned with a given single assessment outcome. Simplified reporting procedures, and the possibility for the Commission to do checks, are among the law’s key innovations.”

Moreover, and very importantly, the Regulation seeks to improve transparency by requiring pharmaceutical companies and academic researchers to publish the results of all their European clinical trials in a publicly-accessible EU database. In contrast to earlier stipulations which only obliged sponsor to publish the end-results of their clinical trials, the new law requires full clinical study reports to be published after a decision on – or withdrawal of – marketing authorization applications. Sponsors who do not comply with these requirements will face fines.

These groundbreaking changes will enter into force 20 days after publication in the Official Journal of the EU. However, it will first apply six months after a new EU portal for the submission of data on clinical trials and the above mentioned EU database have become fully functional. Since this is expected to take at least two years, the Regulation will apply in 2016 at the earliest (with an opt-out choice available until 2018).

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Clinical Trials of Primary Care Drugs: Could Smaller Be Better?

By Kate Greenwood

Cross-Posted at Heath Reform Watch

Lately it seems that each passing day brings another article about the cost of orphan drugs.  Earlier this week at FiercePharma, Tracy Staton reported that the United Kingdom’s National Institute for Health and Clinical Excellence (NICE) has asked Alexion Pharmaceuticals to justify the price of its drug Soliris which is, per Staton, “the most expensive drug in the world” at around $569,000 a year.  Specifically, NICE seeks “‘clarification from the company on aspects of the manufacturing, research and development costs’” of the drug.  According to Staton, this latest development in a review process characterized by “halting progress” is “a departure from NICE’s usual calculations, which typically focus on quality-of-life years and the like.”

Pushback by NICE and other payers notwithstanding, the orphan drug market is growing.  As I blogged about here, in 2013 EvaluatePharma estimated that “the worldwide orphan drug market is set to grow to $127 [billion], a compound annual growth rate of +7.4% per year between 2012 and 2018[,]” which “is double that of the overall prescription drug market, excluding generics, which is set to grow at +3.7% per year.”  In a recent article in the New England Journal of Medicine, venture-capital investors Robert Kocher and Bryan Roberts note that “more than half of the 139 drugs approved by the FDA since 2009 are for orphan diseases” and suggest that there is a risk of “systematically underinvesting in other important areas of medicine.”

Kocher and Roberts’ explain that one reason that orphan drugs attract investment is that their development costs are low.  The problem or potential problem of underinvestment in diseases like depression and diabetes could therefore be addressed, they contend, by bringing the cost of developing treatments for these common conditions in line with the cost of developing treatments for rare diseases.  And, they argue, one promising approach to doing so is to reduce clinical trial costs by reducing the size of clinical trials. Continue reading

Reporting Information about Clinical Trial Data: Passing the Torch from HHS to the FDA

By Leslie Francis

In 2007, motivated by concerns that pharmaceutical companies were not sharing negative data about what had been learned in clinical trials, Congress established enhanced reporting requirements.

A series of articles published in January 2012 in the British Medical Journal demonstrates that data reporting remains deeply problematic, especially for industry-sponsored trials. (The articles can be found here and are very much worth reading).

A posting Sept. 26 in the Federal Register indicates that the Secretary of HHS has delegated authority to to oversee the reporting process to the FDA.  Whether this signals improved monitoring of clinical trial data submissions remains to be seen.  One can only hope.