.tb-grid,.tb-grid>.block-editor-inner-blocks>.block-editor-block-list__layout{display:grid;grid-row-gap:25px;grid-column-gap:25px}.tb-grid-item{background:#d38a03;padding:30px}.tb-grid-column{flex-wrap:wrap}.tb-grid-column>*{width:100%}.tb-grid-column.tb-grid-align-top{width:100%;display:flex;align-content:flex-start}.tb-grid-column.tb-grid-align-center{width:100%;display:flex;align-content:center}.tb-grid-column.tb-grid-align-bottom{width:100%;display:flex;align-content:flex-end} .wpv-view-output[data-toolset-views-view-editor="152a377a3454fef2d5ee6fc13f546a5a"] > .tb-grid-column:nth-of-type(3n + 1) { grid-column: 1 } .wpv-view-output[data-toolset-views-view-editor="152a377a3454fef2d5ee6fc13f546a5a"] > .tb-grid-column:nth-of-type(3n + 2) { grid-column: 2 } .wpv-view-output[data-toolset-views-view-editor="152a377a3454fef2d5ee6fc13f546a5a"] > .tb-grid-column:nth-of-type(3n + 3) { grid-column: 3 } .wpv-view-output[data-toolset-views-view-editor="152a377a3454fef2d5ee6fc13f546a5a"] .js-wpv-loop-wrapper > .tb-grid { grid-template-columns: minmax(0, 0.3333fr) minmax(0, 0.3333fr) minmax(0, 0.3333fr);grid-auto-flow: row } .tb-container .tb-container-inner{width:100%;margin:0 auto} .wp-block-toolset-blocks-container.tb-container[data-toolset-blocks-container="751d72269a9fca740ed3ffe1ce3a8869"] { padding: 0px; }  .tb-image{position:relative;transition:transform 0.25s ease}.wp-block-image .tb-image.aligncenter{margin-left:auto;margin-right:auto}.tb-image img{max-width:100%;height:auto;width:auto;transition:transform 0.25s ease}.tb-image .tb-image-caption-fit-to-image{display:table}.tb-image .tb-image-caption-fit-to-image .tb-image-caption{display:table-caption;caption-side:bottom} .wp-block-image.tb-image[data-toolset-blocks-image="65cce93a6d0a297fd813deea25f9254b"] { max-width: 100%; } .wp-block-image.tb-image[data-toolset-blocks-image="65cce93a6d0a297fd813deea25f9254b"] img { padding: 0px;margin: 0px; }  .tb-container .tb-container-inner{width:100%;margin:0 auto} .wp-block-toolset-blocks-container.tb-container[data-toolset-blocks-container="76b9e19aebd78b467b04c64acfe33167"] { padding: 0px; } .tb-social-share__network{display:inline-block;text-align:center;vertical-align:top;margin-right:7px;margin-bottom:7px}.tb-social-share--092 .tb-social-share__facebook__share-button{cursor:pointer;display:inline-block;background-size:contain;background-color:#3b5998;}.tb-social-share--092 .tb-social-share__linkedin__share-button{cursor:pointer;display:inline-block;background-size:contain;background-color:#007fb1;}.tb-social-share--092 .tb-social-share__twitter__share-button{cursor:pointer;display:inline-block;background-size:contain;background-color:#00aced;}.tb-social-share--092 .tb-social-share__pinterest__share-button{cursor:pointer;display:inline-block;background-size:contain;background-color:#cb2128;}.tb-social-share--092 .tb-social-share__telegram__share-button{cursor:pointer;display:inline-block;background-size:contain;background-color:#37aee2;}.tb-social-share--092 .tb-social-share__reddit__share-button{cursor:pointer;display:inline-block;background-size:contain;background-color:#5f99cf;}.tb-social-share--092 .tb-social-share__viber__share-button{cursor:pointer;display:inline-block;background-size:contain;background-color:#7c529e;}.tb-social-share--092 .tb-social-share__email__share-button{cursor:pointer;display:inline-block;background-size:contain;background-color:#7f7f7f;}.tb-social-share--round .SocialMediaShareButton{border-radius:50%}.tb-social-share__excerpt{display:none}.tb-social-share .SocialMediaShareButton--disabled{opacity:0.65} .tb-social-share[data-toolset-blocks-social-share="5e0e5387fa9ff0ed5c08d011829ff87a"] .SocialMediaShareButton { width: 32px;height: 32px; }  @media only screen and (max-width: 781px) { .tb-grid,.tb-grid>.block-editor-inner-blocks>.block-editor-block-list__layout{display:grid;grid-row-gap:25px;grid-column-gap:25px}.tb-grid-item{background:#d38a03;padding:30px}.tb-grid-column{flex-wrap:wrap}.tb-grid-column>*{width:100%}.tb-grid-column.tb-grid-align-top{width:100%;display:flex;align-content:flex-start}.tb-grid-column.tb-grid-align-center{width:100%;display:flex;align-content:center}.tb-grid-column.tb-grid-align-bottom{width:100%;display:flex;align-content:flex-end} .wpv-view-output[data-toolset-views-view-editor="152a377a3454fef2d5ee6fc13f546a5a"] > .tb-grid-column:nth-of-type(2n + 1) { grid-column: 1 } .wpv-view-output[data-toolset-views-view-editor="152a377a3454fef2d5ee6fc13f546a5a"] > .tb-grid-column:nth-of-type(2n + 2) { grid-column: 2 } .wpv-view-output[data-toolset-views-view-editor="152a377a3454fef2d5ee6fc13f546a5a"] .js-wpv-loop-wrapper > .tb-grid { grid-template-columns: minmax(0, 0.5fr) minmax(0, 0.5fr);grid-auto-flow: row } .tb-container .tb-container-inner{width:100%;margin:0 auto} .wp-block-toolset-blocks-container.tb-container[data-toolset-blocks-container="751d72269a9fca740ed3ffe1ce3a8869"] { padding: 0px;margin: 0px; }  .tb-image{position:relative;transition:transform 0.25s ease}.wp-block-image .tb-image.aligncenter{margin-left:auto;margin-right:auto}.tb-image img{max-width:100%;height:auto;width:auto;transition:transform 0.25s ease}.tb-image .tb-image-caption-fit-to-image{display:table}.tb-image .tb-image-caption-fit-to-image .tb-image-caption{display:table-caption;caption-side:bottom} .wp-block-image.tb-image[data-toolset-blocks-image="65cce93a6d0a297fd813deea25f9254b"] img { padding: 0px;margin-top: 0px;margin-right: 0px;margin-left: 0px; }  .tb-container .tb-container-inner{width:100%;margin:0 auto}.tb-social-share__network{display:inline-block;text-align:center;vertical-align:top;margin-right:7px;margin-bottom:7px}.tb-social-share--092 .tb-social-share__facebook__share-button{cursor:pointer;display:inline-block;background-size:contain;background-color:#3b5998;}.tb-social-share--092 .tb-social-share__linkedin__share-button{cursor:pointer;display:inline-block;background-size:contain;background-color:#007fb1;}.tb-social-share--092 .tb-social-share__twitter__share-button{cursor:pointer;display:inline-block;background-size:contain;background-color:#00aced;}.tb-social-share--092 .tb-social-share__pinterest__share-button{cursor:pointer;display:inline-block;background-size:contain;background-color:#cb2128;}.tb-social-share--092 .tb-social-share__telegram__share-button{cursor:pointer;display:inline-block;background-size:contain;background-color:#37aee2;}.tb-social-share--092 .tb-social-share__reddit__share-button{cursor:pointer;display:inline-block;background-size:contain;background-color:#5f99cf;}.tb-social-share--092 .tb-social-share__viber__share-button{cursor:pointer;display:inline-block;background-size:contain;background-color:#7c529e;}.tb-social-share--092 .tb-social-share__email__share-button{cursor:pointer;display:inline-block;background-size:contain;background-color:#7f7f7f;}.tb-social-share--round .SocialMediaShareButton{border-radius:50%}.tb-social-share__excerpt{display:none}.tb-social-share .SocialMediaShareButton--disabled{opacity:0.65}  } @media only screen and (max-width: 599px) { .tb-grid,.tb-grid>.block-editor-inner-blocks>.block-editor-block-list__layout{display:grid;grid-row-gap:25px;grid-column-gap:25px}.tb-grid-item{background:#d38a03;padding:30px}.tb-grid-column{flex-wrap:wrap}.tb-grid-column>*{width:100%}.tb-grid-column.tb-grid-align-top{width:100%;display:flex;align-content:flex-start}.tb-grid-column.tb-grid-align-center{width:100%;display:flex;align-content:center}.tb-grid-column.tb-grid-align-bottom{width:100%;display:flex;align-content:flex-end} .wpv-view-output[data-toolset-views-view-editor="152a377a3454fef2d5ee6fc13f546a5a"]  > .tb-grid-column:nth-of-type(1n+1) { grid-column: 1 } .wpv-view-output[data-toolset-views-view-editor="152a377a3454fef2d5ee6fc13f546a5a"] .js-wpv-loop-wrapper > .tb-grid { grid-template-columns: minmax(0, 1fr);grid-auto-flow: row } .tb-container .tb-container-inner{width:100%;margin:0 auto} .tb-image{position:relative;transition:transform 0.25s ease}.wp-block-image .tb-image.aligncenter{margin-left:auto;margin-right:auto}.tb-image img{max-width:100%;height:auto;width:auto;transition:transform 0.25s ease}.tb-image .tb-image-caption-fit-to-image{display:table}.tb-image .tb-image-caption-fit-to-image .tb-image-caption{display:table-caption;caption-side:bottom} .tb-container .tb-container-inner{width:100%;margin:0 auto}.tb-social-share__network{display:inline-block;text-align:center;vertical-align:top;margin-right:7px;margin-bottom:7px}.tb-social-share--092 .tb-social-share__facebook__share-button{cursor:pointer;display:inline-block;background-size:contain;background-color:#3b5998;}.tb-social-share--092 .tb-social-share__linkedin__share-button{cursor:pointer;display:inline-block;background-size:contain;background-color:#007fb1;}.tb-social-share--092 .tb-social-share__twitter__share-button{cursor:pointer;display:inline-block;background-size:contain;background-color:#00aced;}.tb-social-share--092 .tb-social-share__pinterest__share-button{cursor:pointer;display:inline-block;background-size:contain;background-color:#cb2128;}.tb-social-share--092 .tb-social-share__telegram__share-button{cursor:pointer;display:inline-block;background-size:contain;background-color:#37aee2;}.tb-social-share--092 .tb-social-share__reddit__share-button{cursor:pointer;display:inline-block;background-size:contain;background-color:#5f99cf;}.tb-social-share--092 .tb-social-share__viber__share-button{cursor:pointer;display:inline-block;background-size:contain;background-color:#7c529e;}.tb-social-share--092 .tb-social-share__email__share-button{cursor:pointer;display:inline-block;background-size:contain;background-color:#7f7f7f;}.tb-social-share--round .SocialMediaShareButton{border-radius:50%}.tb-social-share__excerpt{display:none}.tb-social-share .SocialMediaShareButton--disabled{opacity:0.65}  } 

Behind Rare Disease Day 2017

pharmafile | April 3, 2017 | Feature | Business Services, Manufacturing and Production, Medical Communications, Research and Development, Sales and Marketing | Rare Disease Day, rare disease

Rare Disease Day falls on the last day of February, meaning every four years it occurs on a leap year, chosen as the day itself occurs so rarely; it is particularly apt given that rare diseases generally fall into the shadow of more common ailments, receiving comparatively less publicity and, crucially, research.

The theme of this year’s event was research; its slogan: ‘With research, the possibilities are limitless’. This addresses a core issue for those burdened with rare diseases: with too few individuals suffering from these illnesses, pharmaceutical companies often do not consider them a worthwhile subject of research. Putting drugs through an R&D programme is a prohibitively expensive process, and unless a company believes it can make a solid financial return from its efforts, it is unlikely to proceed.

The promotional video released to promote the day, featuring individuals searching for answers on a search engine, only to be met with no results, was intended to communicate the experience of living with an under-researched rare disease, where patients are left without treatment options due to a lack of essential research.

The pharma industry is now being encouraged to turn its attention to therapies which do not solely benefit such large patient proportions. This has given rise to measures designed to improve patient’s access to ‘orphan drug’ treatments with the Orphan Drug Acts. The first was passed by the FDA in 1983 and amended with the 2002 Rare Diseases Act, while the second, Regulation (EC) No 141/2000, was put forward by the EMA at the end of 1999. In late 2007, both regulatory bodies agreed to increase harmonisation by requiring a common application from both agencies, with the two also agreeing to share treatment data.

It’s a process that still needs fine-tuning; many current discussions tend to centre on price rather than the treatment population or access. Some of the most expensive treatments offered in the world are those that treat rare diseases; according to a report on orphan drugs by EvaluatePharma, the average price tag in the US comes in at $111,820 per year compared with $23,331 for more regular medicines. The prices can become eye-wateringly large, so much so that UK-based regulator NICE has recently implemented strict controls over how high the price of a treatment can potentially go, enforcing a new limit of £300,000 per Quality Adjusted Life Year for any rare disease treatment to be considered for use in the NHS.

However, with progress comes teething issues. Legislation helping to promote research being introduced worldwide, and alongside this, Rare Disease Day has become a global event; the day now occurs in 80 countries worldwide since its inception in 2008, including, for the first time this year, four African nations.

The global development signifies the strength of public sentiment towards improving access to treatment for sufferers of rare diseases. For those involved, Rare Diseases Day goes beyond raising awareness and offers a means of showing support for the difficulties they face on a day-to-day basis. This can be crucially important when many people still face the uncertainty of life without treatment. Pharmafocus spoke to those on the frontline attempting to change patient lives about the work they have been carrying out in this key therapy area.

Alastair Kent, Chair of Rare Disease UK

“It was a very successful day; we had a reception in Westminster with Minister Nicola Blackwood attending. She demonstrated a real understanding of the issues facing families with rare disease because, of course, she has a connective tissue disorder herself and she struggled to get a diagnosis and find out what the problem was. It was very encouraging for the families who were attending the reception to feel that there was a Minister who knew how it really was to face a rare disease. We then had reception in Edinburgh at the Scottish parliament, which was attended by Shona Robison, the Scottish Cabinet Minister for Health and Sport. She was announcing some developments that will hopefully make it easier to for families with rare diseases to access therapies in Scotland – that’s been an issue in the past. We will have to see, but at least there’s been recognition for the need for new ways of thinking about the ways that patients gain access to novel therapies.

It’s an international event now – it’s all around the world. It just gets bigger every year and it’s a real opportunity to highlight how important it is to support families with these conditions. They are in need of properly coordinated services and support.

I think the idea captured a lot of imaginations because there are very many small patient groups who banded together and saw the advantages of coming together in a coherent way to put the issue in front of ministers, politicians, the clinicians and the academic community.

There are something like 8,000 rare diseases, with most of them poorly understood and with no therapies that will change the trajectory of the disease. We need sustained efforts in biomedical research and to translate that research into knowledge, and eventually into therapies that will treat and potentially cure these conditions – but we’re a long way from that.

Our work is a constant campaign to raise awareness of the needs of patients and families to help support research, to improve services, to work with the NHS and to keep the issue on the political front-burner. We support an all-party parliamentary group on rare genetic and undiagnosed conditions in Westminster, and there are cross-party groups in Wales and Scotland as well.

In terms of the pharmaceutical industry, we have always said that we have nothing particularly against high prices if they’re fair prices. I mean, obviously, if you’re developing a therapy that needs a great deal of research and you’re working at the edge of knowledge using complex biological molecules to treat a small patient population then it is likely that the cost will be high. The industry, however, must justify that cost rather than just saying: ‘that’s what we’re going to charge because that’s what the market will bear’. I think there is a danger that if prices keep on rising then the patients will not get access and the steam will come out of the effort to develop novel therapies for patients with these conditions.

I think we need new ways of proving quality, safety and efficacy so that the drugs are regulated in an appropriate way. I think we need greater patient involvement in the process and we need to have earlier and more imaginative dialogue between the industry, the regulators, the health technology assessment bodies and the commissioners so that there can be transparent interaction that’s based on a robust set of principles that we can all buy into.

We’re determined that patient opinion won’t get lost, and if you have the patient voice right from the start, you can be more confident that the therapy is targeted at those aspects of the condition that really makes a difference to patients.”

Yann Le Cam, Chief Executive Officer, EURORDIS – Rare Diseases Europe

“Rare Disease Day 2017, the tenth edition of Rare Disease Day, was an unprecedented success; events took place in 94 countries around the world, including in Botswana, Nigeria, Senegal and Sudan for the first time!

On 28 February, I participated in a media event at the University Hospital in Leuven, Belgium, for the launch of the new European Reference Networks. These 24 European Reference Networks for rare diseases are virtual networks bringing together nearly 1,000 healthcare providers across Europe to tackle complex or rare medical conditions that require highly specialised treatment with both a concentration on and sharing of knowledge and resources.

The reason behind the day was because awareness of the impact of rare diseases on daily life was low; we needed something to help raise awareness among politicians, healthcare providers, researchers and pharmaceutical companies. Rare Disease Day contributes to break the isolation of patients and families around the world, to promote their recognition in society and empower them. There was also a need to bring the rare disease community together.

Rare Disease Day is a patient-led campaign that EURORDIS and its Council of National Alliances launched in 2008. The day has helped us to achieve exactly what we hoped. Ten years later, awareness is up and the community is stronger and better connected than ever before.

Rare Disease Day is a grassroots campaign. Nearly 40 rare disease national alliances came together to coordinate the theme and slogan for Rare Disease Day 2016. Supported by an ever-growing global community, it is no surprise that over the last ten years Rare Disease Day has become iconic as the global campaign for raising awareness of rare diseases among politicians, clinicians, researchers and pharmaceutical companies.

Since 2008, thousands of patient organisations in over 100 countries and regions have held tens of thousands of events. Rare Disease Day brings together millions of patients, families, carers, medical professionals, policy makers and members of the public in solidarity.

The major difficulties that patients with rare diseases face is the months or years that it can take to get a diagnosis, the possibility of misdiagnosis or the reality of living with an undiagnosed disease forever. Then, once diagnosed, being unable to get information on the disease or find other people living with the same disease or even a doctor with knowledge on the disease, later finding out there is no cure or treatment. Or when there is a treatment, that it is not available to patients because it has been held up by the national healthcare authorities because of lack of clinical data or because of pricing issues. A rare disease can also have a huge effect on the school, work or social lives of the individual and their family. These are only some of the challenges that people face on a daily basis.

By connecting patients, families and patient groups, as well as by bringing together all stakeholders and mobilising the rare disease community, EURORDIS strengthens the patient voice and shapes research, policies and patient services.

Our vision is to enable better lives and cures for people living with a rare disease and our mission is to work across borders and diseases to improve the lives of people living with a rare disease.

Even though ever-advancing science and technology now creates rapidly growing opportunities to develop more innovative medicines, the rare disease community is still facing problems accessing these medicines in Europe because of their affordability.

National health authorities need to recognise that, because of the very small number of patients in each country – usually only a handful or up to few hundred – it does not make sense to negotiate prices or collect real-world evidence at a local level. There needs to be coordination at a European level.

EURORDIS is calling for change to the procurement system to ensure that medicines are immediately accessible to patients and affordable and sustainable for national healthcare systems. The system should create a predictable and sustainable environment for companies and investors.

This change will not be easy but it is urgently needed to translate innovation into health benefits for patients. Improving access can only be achieved by establishing a collaborative multi-stakeholder-structured approach.

Collectively, we should aim for the goal of a three to fivefold increase in the number of rare disease medicines approved by the EMA per year by 2025, with those medicines available at one third to one fifth of the price.

To achieve this, we need collective, multi-stakeholder negotiation that is based on the interests of all parties involved. Pharmaceutical companies, as well as researchers and scientists, the EMA, and national competent authorities that carry out health technology or pricing assessments must all accept that there will be wins and losses for everyone involved. In the end we must find a new deal that ultimately ensures that patients can access medicines so that the devastating impact of rare diseases is reduced.”