Celebrating 10 Years of the Orphan Drug Regulation in Europe

pillsThe European Orphan Drug Regulation celebrates its 10th Anniversary this year – an opportunity to reflect on the experiences gained and the challenges ahead.

“Overall the Regulation can be considered a success. It has led to medicinal products coming to market for rare conditions previously untreatable, transforming the lives of the sick and dependent, as well as improving quality of life and survival”, says Lesley Greene, a former EURORDIS President and current member of the Committee for Orphan Medicinal Products (COMP).

It has contributed to boosting research, development and marketing of orphan medicinal products in Europe. Since its adoption, more than 1,000 applications for orphan drug status have been reviewed and the number of new applications is rising every year. In 10 years, 728 have been designated as ‘orphan drugs’ and 60 have received marketing authorisation. Of this, around 2.5-2.6 million patients potentially stand to benefit. The consolidated trend indicates that an average of 10 new orphan medicines will be approved for marketing every year in EU over the next 5 to 10 years.

Fabrizia Bignami, EURORDIS patient representative on the Committee for Advanced Therapies (CAT) at the European Medicines Agency

What kinds of products are designated? The majority are designated for rare cancers (46%), metabolic diseases (10%), cardiovascular and respiratory diseases (9%), to mention a few therapeutic areas.

In terms of prevalence more than half of designations are for conditions that affect between 1-3/10,000 persons in the population which is far below the cut off for the epidemiological definition of rare diseases (5/10,000) – therefore potentially addressing the needs of very rare conditions. “It could be said that the Regulation has stimulated research into rare and very rare diseases, which has not only led to potential treatments in these areas but also cascaded new knowledge of the causes and possible prevention and therapies for both less rare and common conditions,” explains Lesley Greene.

Indeed the Orphan Drug Regulation has fostered innovation. Over the years a steady increase has been observed in advanced therapy medicinal products such as cell, gene and tissue based products, now reaching up to 7% of all designated products. Overall, approximately 30% of orphan drug designations are classified as innovative.“The EU Regulation on Orphan Drugs has played its full role, beyond our expectations of 12 years ago. The Regulation is a powerful instrument to incentivise and channel investments in therapeutic areas where perspectives on return on investment were not sufficient under normal market conditions. Though this is not sufficient to address the huge medical needs rare disease patients are facing, we now know that the drivers for rare disease therapies are the co-existence of patient groups for the disease, of a patient registry and of a European network of researchers or clinicians: it is timely to better articulate policies in drug development with EU research and public health policy,” adds Yann Le Cam, EURORDIS’ Chief Executive and former COMP Vice Chair.

In addition, the incentives that were built into the Regulation have had a positive impact on drug development and have helped accelerate the time to approval of market application. Scientific Advice (or Protocol Assistance for orphan drugs) provides the opportunity for drug developers to optimise their research and development plans and reduce uncertainties in regulatory outcomes.

Sylvia & pillsThe Regulation has also benefited the biotech industry and small and medium-sized companies, in particular, which have been able to attract venture capital to take their products forward from the bench to the bedside, thanks to the economic and scientific incentives provided by the Orphan Drug Regulation. The Regulation is enhancing EU health innovation capacity and industry competitiveness while creating high added value jobs.

In the same way, sponsors with an orphan drug designation benefit from fee reductions (or waivers) for various regulatory procedures, such as protocol assistance, application for marketing authorisation and post-authorisation activities at the European Medicine Agency. In addition, the common FDA/EMA orphan designation application has reduced the administrative burden.

However, there is still room for improvement. There is a clear need for more orphan drugs for unmet medical needs. “Sixty orphan drugs for the estimated 6,000-7,000 rare diseases are clearly not enough. Companies could be oriented to areas where there is lack of treatment in order to focus their research efforts,” argues Fabrizia Bignami, Therapeutic Development Director at EURORDIS. “There is also a crying need for more basic research into diseases with no current investigation and no drug treatment on the horizon. For this reason the collection of data on off-label use of approved orphan drugs and other medicines would be useful”.

“Every year, medicines for frequent indications are withdrawn from the market because they are off-patent, not profitable anymore and new innovative products have been introduced. Still, many of these medicines have a non-medically validated off-label use for orphan conditions, which is life saving or significantly improving the lives of people living with these rare conditions. We need to find ways to identify systematically these drugs and to study their off-label uses, so that, if results are positive, a more favourable environment can be created to keep the product on the market” argues Yann Le Cam. “We hope that, in the future, the European Medicines Agency will play a key role in identifying the gaps in medicine development, such as analysing the reasons for discontinuation of the development of designated orphan drugs, and propose remedial action”.

EMA 10 year OD RegulationAnother significant challenge remains to translate market authorisations into real availability for patients in every Member State. A survey on drug availability conducted by EURORDIS in 2007, revealed that most countries with smaller populations suffer from longer delays in availability of orphan drugs, and in some countries with high GDP, there are only a small number of drugs genuinely available.

“The biggest challenge and threat will remain equitable access because of cost and national health policy that views drugs in terms of budget instead of their clinical added value,” says Lesley Greene. “This in turn, could become a disincentive to industry to pursue the challenge of orphan drug development, so much so that we return to the situation that existed two decades ago.”

This is why EURORDIS, industry and academic leaders have been advocating for common scientific assessment of the clinical added value of orphan drugs, associated with Benefit Management Plans (gathering post marketing research activities agreed by Member States), as well as conditional pricing policies in order to harmonise and speed up pricing and reimbursement decisions in all Member States. Together, they are advocating for the prompt creation of a Working Party at the European Medicines Agency for these Clinical Added Value Assessment activities.

In the words of Lesley Greene: “Solutions for rare diseases are no longer just in our minds, they are on the map and on the march!”

For more information:

Conference announcement “10 years of the Orphan Regulation in Europe”, EMA, January 2010

EPPOSI 11th Workshop on Partnering for Rare Disease Therapy Development – “10 years after the adoption of the EU Orphan Medicines Regulation: Where do we go?”

This article was first published in the June 2010 issue of the EURORDIS newsletter

Author: Paloma Tejada
Photo credits: © EURORDIS

Page created: 24/05/2010
Page last updated: 13/03/2012
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