Inside view: rising to the challenges of orphan drug development

Paul Tunnah interviews Wills Hughes-Wilson


Working in the rare disease space presents a number of challenges for pharma – low patient numbers and lack of disease awareness hinder development activities, whilst cost-containment measures in many countries can present major obstacles to ensuring access to novel treatments. Nevertheless, there are a significant number of rare diseases affecting millions of patients globally each year, many of which still lack any form of adequate pharmacotherapy.

Ahead of her presentation at the upcoming Orphan drugs summit 2011, pharmaphorum spoke with Wills Hughes-Wilson, Vice President for Policy in Europe at Genzyme, to understand more about the challenges and opportunities presented by developing drugs for the rare disease space. During our discussion, we explored the regulatory landscape around orphan drugs, the collaborative nature of working in this space and what success looks like for pharma, healthcare providers and the patient.

To listen to the full interview, please click on the play button below, with a shortened transcript of some edited highlights shown in print below.

Interview summary

PT: Hello Wills and thanks for joining me. Now you’re currently Vice President for Health Policy in Europe at Genzyme, so what kind of business activities does that principally entail?

WHW: I’m responsible for creating an external environment ensuring patients can get access to treatment, working with external stakeholders, my colleagues and also other companies in the rare disease space. One of the most interesting things we have been doing together recently is being part of setting up the EU Committee of Experts on Rare Diseases. This has been established by the European Commission and it brings together representatives from all stakeholders — every EU Member State, academics, patients and the industry working together as part of that committee to create an external policy programme that will hopefully improve the diagnosis, treatment and care for rare disease patients in Europe. We’re also working together via the joint industry taskforce on orphan drugs and rare diseases, jointly coordinated by EBE and EuropaBio, the two trade associations here in Brussels. So it’s a very collaborative job and that’s one of the hallmarks of the rare disease space.

“…it’s a very collaborative job and that’s one of the hallmarks of the rare disease space.”

PT: How do you define something as an orphan drug?

WHW: Many countries have decided that orphan drugs are an area that’s worthy of support, but the exact definition differs from region to region. In the US, for example, it was a cut-off figure of a finite number of 200,000 patients, whereas in the European Union it’s a prevalence figure of five in 10,000 patients. But from a European perspective there are other specific clauses that say you have to prove that not only are you developing a drug for a disease that is rare, but it also has to be chronically debilitating or life-threatening. In addition, it either has to be without existing satisfactory treatment, or you have to show that what you’re bringing to the market offers significant benefit, so something better for the patients in question. And you have to prove that in clinical trials. Rarity is not enough.

PT: So clearly significant for the patients, but from the drug developers’ perspective what benefits come with being granted orphan drug status?

WHW: Again those differ according to country or region, but there are incentives to encourage companies. In Europe we have benefits that are contained in the Orphan Regulation up to the Marketing Authorisation stage, so during your development phase you could ask for protocol assistance (which is free scientific advice from the European Medicines Agency) on how to design your clinical trials. You can also benefit from fee waivers or reductions for the development and marketing authorisation process. Beyond that you also have “market exclusivity” – this one always makes me smile a little bit because the name would suggest some form of monopoly! But that is not the case. You could have a situation where there is no existing treatment, but if there is another treatment, the new treatment has to prove that it brings a significant benfit. So it is always possible to break the “Market Exclusivity” if you bring a significant benefit So the market exclusivity is more of a psychological benefit, because it can be broken. For example, there are four or five treatments for pulmonary arterial hypertension here in Europe and multiple treatments even in very rare diseases, such as the diseases we treat.

“…patients suffering from rare diseases deserve the same level of quality, safety and efficacy for their drugs as any other patient.”

PT: How do these incentives impact on the cost of developing orphan drugs?

WHW: One of the main starting points from a European legislative perspective is that the patients suffering from rare diseases deserve the same level of quality, safety and efficacy for their drugs as any other patient. So that means getting a product through the European system. But beyond that, there are multiple, very specific challenges in the rare disease space. Right from early discovery, the development of an orphan medicinal product is often accompanied by only partial knowledge of the disease in question. Y ou may not have strong animal models or the technical support found in more common diseases. When you get to clinical trials, you have to bring together small populations of eligible patients, which might be scattered widely and internationally, and a lot of rare diseases affect children, so you have to also bring their families or carers to the centres as well. For marketing authorisation registration you may have quite a complicated dossier with a rather small data-set, so you have to work with the regulators to try and understand what the evidence shows and what needs to be demonstrated after the positive risk-benefit analysis has been made. After the marketing authorisation, we very often have follow-up studies, registries and an on-going commitment to educate the treating community at large, because disease awareness remains very low until there’s a treatment available. So there are challenges at every stage of the development process and any company that wants to be in this area really has to be in it for the long-haul.

PT: So you have extensive development costs and expensive educational programs but small patient populations, resulting in a higher drug price point to make it commercially viable. How do you deal with the market access challenges that presents?

WHW: It’s true that many orphan drugs coming to market do have a higher price point than you would see for most common diseases. So we need an on-going dialogue with all stakeholders to create sustainable long-term market access programmes at country level. We also have to remember that the people making decisions about pricing and reimbursement are just trying to do their job, to make sure tax-payers money is spent in the most cost-effective and responsible way. So our role is to help the governments understand the impact of a disease, the clinical benefits and relevance of a treatment to the patients and to help them understand that this is a very defined population. We need to continue that dialogue as we have done over the past 10 years to find shared solutions. A lot of governments are looking at the success of the orphan drug Regulation here in Europe, where we have around 70 drugs that have received a positive opinion since the enactment of the Regulation in 2000. Governments are trying to work out how to deal with the number of orphan drugs currently and in the future, and the only way we can do this is to figure it out together. That’s one of the nice things about working for Genzyme – we’ve always had the reputation of being collaborative and part of a community that’s working on these shared solutions. Since about 2008 there’s been an increasing collaborative dialogue between the countries in Europe and the other stakeholders about something that essentially amounts to coverage with evidence development for orphan drugs, and these proposals are in development even as we speak, so we’re hoping to see concrete advances in the next six to 18 months.

“…our role is to help the governments understand the impact of a disease, the clinical benefits and relevance of a treatment to the patients…”

PT: So does the current regulatory framework go far enough to support drug development in these areas?

WHW: This is a very, very complex field and I would argue that the European regulatory framework is extremely strong, does the job and should be safeguarded. Of course there are challenges across discovery, development, marketing authorisation and market access, but the orphan drug regulation in Europe is delivering the goods and should be respected. The next part of the framework is in the hands of the Member States, because each must decide which patient populations to treat and how they spend their money. So it is not so much the Regulatory framework. The Regulation is working, but we need to keep working with the countries to ensure national plans allow patients to get access to the right drugs that make a difference. We’re not going to overcome scientific challenges by a regulatory framework, only by collaborating at all levels and stages to make headway into the vast majority of rare diseases that don’t have an effective treatment yet.

Seventy orphan drugs is a nice start but there are thousands of rare diseases out there without any kind of treatment and that’s what we need to continue to work on.


1. EUCERD – European Union Committee of Experts on Rare Diseases (

2. EBE – European Biopharmaceutical Enterprises (

3. EuropaBio – European Association for BioIndustries (

About the interviewee:

Wills Hughes-Wilson is Vice President, Health Policy Europe at Genzyme. She joined Genzyme in September 2005. In her role, Hughes-Wilson is responsible for health policy, including activities related to market access and reimbursed patient access in Europe for Genzyme’s product portfolio. She leads and coordinates the European and EU-based activities in this respect, working with a network across the company, including chairing Genzyme’s European Market Access Committee – a cross-functional leadership group reporting to the President of Europe.

She has led advocacy activities on a range of issues of importance to the company and its patients, in particular advanced therapies and orphan medicinal products, including market access aspects and the future of the EU frameworks relating to these fields.

Hughes-Wilson is one of the 4 industry members of the European Commission’s newly established EU Committee of Experts on Rare Diseases (EUCERD) and is Chair of the joint EBE and EuropaBio Industry Task Force on Orphan Drugs &amp, Rare Diseases and is an active member of the key industry working groups related to HTA and market access in the European trade associations. She is a Member of the Board of EuropaBio, the European Association for BioIndustries.

Wills will be speaking at the upcoming Orphan drugs summit 2011.

How can rare disease drug development be improved?