Main Lessons from the World Orphan Drug Congress USA 2019

Many orphan drugs are advanced therapies. Pricing and access are major issues. Epilepsy is catching up with gene therapy. We shouldn’t call them rare diseases, but frequently misdiagnosed diseases. Either we wait 2,000 years for treatments or we start thinking “many diseases at a time”, and online patient communities are now part of the drug development process.

That’s the short summary of the main lessons I took home from attending the World Orphan Drug Congress at the National Harbor April 10-12. The WODC one of the largest meetings dedicated to the development of new medicines for rare diseases and takes place once in the US and once in Europe every year. 

In a bit more detail, here is the expanded list of what I would like to share with you from the conference:

1- A lot of “orphan drugs” use new technologies.

Although the Orphan Drug Act was conceived to stimulate development of therapies for rare diseases in general, and it has often been used in an “opportunistic way” for drugs that could have targeted broader populations, the new technologies that allow us to target specific gene defects are taking over the field. There was an entire day on Next Generation Therapies that highlighted programs in development using antisense, base editing, gene therapy and cell therapy approaches. There was also a great plenary session with multiple of these approaches including companies already in the clinic such as AlnylamSangamo Therapeutics and CRISPR Therapeutics

I believe that with most rare diseases having a genetic cause, and most genetic diseases being rare diseases, it is only natural that gene-targeting technologies will find their home in the rare disease space.


2- Big challenges: delivery, manufacturing and drug pricing 

In many of the debates the conversation went beyond the medical use of these new technologies and focused on some important challenges that the orphan drug community needs to face and address. One important issue that multiple of the new technologies face is how to get into their target tissue. This is particular complex for neurological diseases, although some companies are making great progresses in this space and Alnylam announced a few days before the WODC a partnership with Regeneron to apply their RNAi therapeutics to ocular and neurological diseasesManufacturing challenges also limit cell and gene therapy development, making many of these one-time treatments too expensive. And that was indeed one of the main topics of discussion in the meeting: pricing and affordability of these new therapiesEmil Kakkis from Ultragenyx stressed the importance of ensuring access to therapies saying that this is the golden age for rare diseases and yet a therapy means nothing if patients cannot get access to it. While delivery and manufacturing are technical challenges, identifying suitable payment mechanisms that guarantee patients access to treatments is a social challenge that is likely to be the hardest to address. 

3 – Epilepsy meets the future

I regularly participate in orphan drug conferences, where I get to see all these exciting new technologies, yet at the epilepsy conferences (my field) most of what we see is traditional pharmacology that focuses on reducing brain activity without targeting the specific cause of the epilepsy in that patient. I work on neurological syndromes with epilepsy, and a very large number are monogenetic meaning that they would be the ideal target for these new approaches. Barry Ticho from Stoke Therapeutics said it very clearly at the WODC:

there are more than 100 epilepsy genes but not a single therapy that treats the causes”.

But that is changing.

At the WODC we could see multiple approaches in development to specifically target the causes of several neurodevelopmental syndromes with epilepsy. In addition to Stoke presenting their antisense approach for Dravet syndrome, the small company RogCon presented their antisense approach for SCN2A epilepsies, Roche presented their antisense approach for Angelman syndrome, and as part of a panel, Xenon Pharma highlighted their small molecule approach with a potassium channel opener for KCNQ2 epilepsy. This is a good reminder that for some genetic diseases, small molecules could also offer an excellent disease-targeting approach, as also seen in cystic fibrosis where different CFTR protein alterations are treated by specific molecules designed to address those alterations.


To prepare the field of epilepsy for these new personalized approaches, early genetic diagnostic is paramount. Invitae has now extended the Beyond the Seizure epilepsy program to offer free genetic testing to all US children under 60 months of age with epilepsy. This program is sponsored by BioMarin, Stoke and Xenon, and I hope it will get more sponsorship to be opened to patients currently older than 5 years old and from other countries. Having a genetic diagnosis (early or not) is still one of the big challenges for rare disease patients around the world. 

4- Don’t call them rare – the importance of the words we use

Carol-Anne Partridgeis the Founder of a patient charity, and the mother of a beautiful girl with CDKL5 Deficiency Disorder. In her presentations, Carol-Anne always stresses that we need to change the narrative around rare diseases. Her experience resonates with that of many other people with rare diseases and their families, tired of a focus on what they cannot do (instead of what they can do, or the future cures they will have), and physicians talking in front of their kids in a way that doesn’t respect them. We need to change the narrative to one of hope and positivity and respect for people with rare diseases.

Arndt Rolfs, CEO of Centogene, made a similar plead to the WODC audience about the need to change the narrative. If we call them rare diseases, he explained, physicians will think that they will never across one, so they will not watch out for rare diseases. We should call them frequently misdiagnosed diseases instead, so that physicians are particularly alert to not miss them. This makes so much sense, and has such important consequences to patient diagnosis, that we should all start using the “frequently misdiagnosed diseases” term a lot more often.

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With his presentation, Dr Rolds echoes Carol-Anne’s message: we need to change the narrative around rare diseases if we want to diagnose, treat and respect people with rare diseases.

5 – Reshaping “Rare” by thinking “many diseases at a time”

Chris Austin, Director of NCATS, gave one of my favorite presentations at the WODC about reshaping “rare”. At the current rate of orphan drug approval it will take 2,000 years before we have treatments for all rare diseases (assuming each new drug is approved for a different rare disease, which is not the case). A radical change in the way we discover and develop these therapies is needed. Chris’ proposal is to move from working on “one disease at a time” to working on “many diseases at a time”, exploiting commonalities among rare diseases and platform technologies to diagnose them and treat them. NCATS has multiple initiatives around this “many diseases at a time” approach, from empowering patient communities to get active in research to providing guidance on interoperable registries and partnering in drug development, including developing a gene therapy platform. 

While Chris advocated for these multiplexing approaches to diagnosis and therapy development, I think that we will need some regulatory innovation to address the challenge that in some fields companies are forced to run pivotal trials in a rare disease at a time, making it not viable for companies to run trials in ultra-rare diseases and condemning these patients to off-label drug use (more thoughts on this regulatory challenge here). 

6 – The place for social media and on-line patient platforms in orphan drug development

An interesting topic that also was present in different tracks at the WODC was the importance of social media and digital platforms in research and development. Luke RosenHead of Patient Engagement at Ovid Therapeutics, explained how Ovid believes that listening to the patient community voice is crucial for companies to understand what truly matters to families affected by rare diseases, and how Ovid is supporting the conversation by helping create community sites. A patient community that comes together becomes a stronger community, and an essential part of the drug development process. And Luke understands this well because he is also the Founder of the Foundation to develop therapies for his daughter and other children with KIF1A associated neurological disorder. 


We also had a workshop during the first day of the WODC, where I participated, where we reviewed how on-line communities are able to capture the patient voice in a way that is directly usable for drug development

DuchenneXchange, for example, was created to help connect, educate and inform the Duchenne muscular dystrophy community, and James Valentine explained how regulators appreciate the use of on-line platforms to collect patient experience and preference data that will be useful for regulatory purposes. In fact in the FDA guidelines for Patient Focused Drug Development meetings, one of the methodologies for collecting patient experience data are precisely “Social Media and Identifiable Patient Communities”.


And “community” is perhaps the main value of the World Orphan Drug Congress. As much as I enjoy the workshops and presentations and roundtables, the main value I get from attending the WODC is the network. I get to catch up face to face with people I already knew, and I get to meet new people from promising companies or related patient communities.

See you all next year!

Ana Mingorance PhD