Q&A with Hartmann Wellhoefer, Shire's VP and Head of Medical Affairs; Rare Diseases & Internal Medic


Hartmann Wellhoefer, M.D., head of medical affairs at Shire, recently sat down with Rare Disease Report to discuss the company's recent work for the rare disease community, particularly lysosomal storage diseases.

Hartmann Wellhoefer

Hartmann Wellhoefer, M.D., VP and Head of Medical Affairs, Rare Diseases & Internal Medicine at Shire, recently sat down with Rare Disease Report to discuss the company's recent work for the rare disease community, particularly lysosomal storage diseases.

Rare Disease Report: Can you provide a quick overview of Shire’s current work in rare disease?

Hartmann Wellhoefer, MD: Shire is the leader in rare diseases which is reflected in our pipeline of more than 40 projects in pre-clinical stages and roughly 40 projects in clinical stage development. Out of these, more than 70% of the clinical pipeline are designated orphan drugs for rare diseases.

RDR: What are some of the biggest areas of progress that the industry has seen in the rare disease space?

HW: There are a few areas of exciting progress, in my perspective.

First, innovation and technology have played a major role, in particular for the advancement of genetic testing. These tests have become increasingly affordable, faster, and much more accurate.1 With these tests, patients can be diagnosed earlier and, where appropriate, can be treated earlier, which is often important. Since 2014, Shire has provided testing support to almost a quarter of a million people around the globe, helping lead to diagnoses of about 4,000 patients with lysosomal storage disorders (LSDs).2

Second, progress has been seen with the advancement of the digital space and “big data,” where we have just begun to scratch the surface. You can see the implications of this real-world data in a current initiative Shire is leading called the “Global Commission to End the Diagnostic Odyssey for Children.” In this initiative, we have teamed up with Microsoft and EURORDIS to develop a roadmap for shortening the diagnostic journey for rare disease patients to ultimately guide the rare disease field in accelerating time to diagnosis.

Finally, increasing patient involvement in the drug development process has become a critical element for the industry. Patients and their caregivers increasingly have a voice in the drug development process and provide insights to industry and regulatory bodies,3 which is tremendously valuable.

RDR: What are some of the challenges facing the development of treatments for rare disease?

HW: Despite some of the major areas of progress, we are still faced with some fundamental challenges. One major challenge is access to and availability of data, and the sensitivities around data privacy. As an example, when it comes to natural history studies — which are critical in helping us understanding the typical progression of a rare disease – in many cases there are no existing data, or it’s very difficult to access due to privacy protocols. So sometimes we have to initiate a natural history study at the same time as we may be initiating a Phase I or Phase II study in an orphan indication.

One of the ways Shire is addressing the challenges we face is by publishing our data in open-access journals, an announcement we made earlier this year. In other words, any data that Shire publishes will be done so in a format that anyone around the world can access for free. As the first pharmaceutical company to do this, we want to set the stage for transparency about what we do, how we collaborate, and the role of patients and their caregivers in the development process. In this way, we can promote a better understanding about the data, and further engagement by the patient community in what we do with the data.

RDR: Earlier this year, Shire presented some of its work in rare diseases at the 2018 WORLDSymposium. Can you tell us a little bit about the company’s current work in lysosomal storage disorders (LSDs)?

HW: We have several programs in the LSD space, including Fabry disease, type 1 Gaucher disease, Hunter syndrome (also known as Mucopolysaccharidosis type II, or MPS II), and Metachromatic leukodystrophy, also known as MLD. Across all the programs we have for LSDs one of our major focuses is studying long-term benefit and risk outcomes.

In terms of research and development updates, we also presented data from our investigational, intrathecal program (SHP609*) for Hunter syndrome, as well as for MLD (SHP611*). For the latter we presented further analyses of previously presented Phase I/II data that hopefully will help us define the path for a pivotal Phase III study in the future.

(*Note to reader: SHP609 and SHP611 have not been approved for use by the U.S. Food and Drug Administration, European Medicines Agency, or other regulatory authorities.)

RDR: Can you summarize the top-line results of SHP609 for children with Hunter syndrome and cognitive impairment that was presented at WORLD?

HW: About two-thirds of Hunter patients have a neuronopathic form of the disease that affects their central nervous system and brain function.4 Shire has been working on addressing this issue — the next frontier for Hunter syndrome – for roughly 20 years.

The top-line results of our Phase II/III study of SHP609 in children with Hunter syndrome and cognitive impairment were presented earlier this year by the Principal Investigator, Professor Joseph Muenzer, at WORLD. The presentation summarized the primary results that we announced in December 2017 from this trial. In this trial, SHP609 was administered to patients using a device that delivers the therapy directly into the cerebrospinal fluid as a means of getting the drug to the central nervous system.

Unfortunately, the top-line data from this study didn’t show the results that we had hoped for. We did not meet the primary and key secondary endpoints. Obviously, this was a disappointment to us and to the community.

However, we are continuing to keep the Hunter community informed and are working closely with regulatory authorities to hopefully define a path forward after the initially disappointing results.

RDR: What are some of Shire’s biggest takeaways to date from this clinical trial on SHP609 for children with Hunter syndrome and cognitive impairment?

HW: One of the things that we’ve learned is the huge variability among pediatric patients. One Hunter syndrome child is very different from another in terms of the progression of the disease — especially the neuro-cognitive aspects of it. The variability that we found in the children from the study was just striking. The variability in disease progression was much stronger than we had predicted based on the publications and research available when we designed the trial, more than eight years ago.

RDR: What are Shire’s next steps for this study of SHP609 for children with Hunter syndrome and cognitive impairment?

HW: At this point, treatment for patients in the Phase I/II and Phase II/III extension trial will continue. Shire encourages families whose children are receiving treatment to contact their treating physician with any questions.

Since announcing the top-line data in December 2017, we have done a tremendous amount of work to better understand the data that we have. Shire is hoping to have further information for the Hunter syndrome community of patients, caregivers and physicians later this year when we expect to have more data from the ongoing extension study.

In the meantime, our clinical development colleagues, in collaboration with our biostatistician teams, are working on examining the totality of the data. We are continuing to analyze the data, and speak with the trial investigators and relevant regulatory authorities to find a potential path forward for this investigational treatment.

RDR: What motivates you and your colleagues at Shire to continue to pursue the work that you do in rare disease?

HW: Patients, patients, and patients, as well as innovation.

We are a very patient-focused organization. There isn’t a week that goes by where I don’t get an email or phone call about a rare disease patient who needs our help with their disease. Very often we get requests about some of the other thousands of rare diseases that have no current treatment. For myself and my other colleagues at Shire, hearing or reading about these patients and families and their challenges — and sometimes meeting them in person – is what drives us out of bed every morning.

We are also driven by innovation — the desire to develop new, novel, and advanced treatments and technology that could make a difference.

I am personally very proud to work at Shire because we make a difference in the lives of patients. But we also know we’ve only provided a proper diagnosis to a fraction of the patients out there, and we are only providing therapy to a fraction of those who need treatment. So, there is a huge amount of work that still needs to get done. For Shire — and I’m sure I speak for all my colleagues, that is more than enough motivation to focus on patients and innovation in science and clinical medicine.


1. Durmaz, A.A. Karaca, E. Demkow U, et al. Evolution of Genetic Techniques: Past, Present, and Beyond. BioMed Research International. Hindawi Publishing Company. 2015; 461524.

2. Shire. 2016 Annual Responsibility Review. Accessed March 12 2018. https://www.shire.com.tr/-/media/shire/shireglobal/shirecom/pdffiles/newsroom/global%20files/shire-annual-responsibility-review.pdf?la=en&hash=8AF2EE4718C346D706E40374ADE659B844798513

3. U.S. Food and Drug Administration. Taking New Steps to Meet the Challenges of Rare Diseases- FDA Marks the 11th Rare Disease Day. February 26 2018. Accessed March 12 2018. https://blogs.fda.gov/fdavoice/index.php/2018/02/taking-new-steps-to-meet-the-challenges-of-rare-diseases-fda-marks-the-11th-rare-disease-day/

4. Muenzer J et al. A phase I/II study of intrathecal idursulfase IT in children with severe mucopolysaccharidosis II. Genet Med. 18(1):73-81.

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