Read the Conversation
Meeting highlights:
- Pipeline Focus and German Involvement: Ultragenyx has a strong pipeline for rare metabolic diseases, including several gene therapies. German investigators play a role in several clinical trials, reinforcing Germany’s role in innovation.
- Challenges with Regulatory Environment: Recent German health policies have complicated market access and increased pricing pressures, making it harder to launch new treatments and hindering access to innovative therapies.
- Importance of Early Diagnosis: Schulze emphasizes newborn genetic screening and improved referral systems to identify rare diseases earlier, which is crucial for treatment and quality of life.
- Collaborative Approach: Ultragenyx advocates for partnerships with other companies, professional societies, and patient groups to raise awareness and improve diagnostics for rare diseases.
- Need for Financial Support: Schulze calls for renewed venture capital interest in biotech, as sustainable investment is crucial for long-term innovation, especially in rare disease research and development.
EF: How have things evolved over the past two years since we last met, and what are the current priorities on your agenda?
RS: Ultragenyx has successfully created a drug that addresses an important unmet need in homozygous familial hypercholesterolemia. At the same time, we're moving forward with our research pipeline, as Ultragenyx remains focused on innovation. We are conducting clinical trials for six different rare diseases, most with participating German investigators. For example, the clinical study for long-chain fatty acid oxidation disorders is now fully enrolled, as is the study on osteogenesis imperfecta. We’re also progressing programs for glycogen storage disease type 1A (GSDIa), ornithine transcarbamylase deficiency, Wilson’s disease, and gene therapy for mucopolysaccharidosis type IIIA, a very severe lysosomal storage disease for which there is no specific treatment, yet. Another promising development is the antisense oligonucleotide for treating Angelman syndrome that has started to enroll patients for a Phase 3 study, with several German sites involved.
EF: How do you assess the national pharma strategy from a rare disease company's perspective?
RS: It's a step in the right direction. The German government has begun to recognize that the pharmaceutical industry can create high value with minimal energy use. Due to Germany's intentionally high energy costs, Germany has lost competitiveness in several other sectors. While I'm not entirely sure about our current competitiveness in pharmaceuticals, it's clear that improvements are needed, especially after the major setbacks following the act on stabilizing statutory health insurance financing (GKVFinStG). This has unnecessarily made access to much-needed innovation more challenging.
EF: How can we address late diagnosis and the clear shortfall in younger people and children, and how can policy and education be enhanced to push earlier and more accurate diagnostics, especially regarding rare diseases?
RS: We could learn from countries that diagnose patients faster, allowing earlier treatment, better quality of life, and in many cases longer life expectancy. The gold standard for early diagnosis is newborn screening. In Germany, the process to include more diseases in newborn screening is unfortunately very slow and has not kept up with recent progress in science. Take lysosomal storage disorders, for example, which are currently not part of general newborn screening. Some of these conditions come with severe cognitive impairment and other neurological symptoms. With current therapeutic interventions, deterioration of neurological function can be prevented in many patients. Therefore, it is crucial to detect these patients at a very young age. With generalized genetic newborn screening, finding these patients before the emergence of irreversible symptoms seems much more likely. Despite the advances in big data analysis and artificial intelligence, the time to establish the right diagnosis is still much too long - many patients still go through a revolving door of specialists without getting real answers, particularly in diseases with apparently unspecific symptoms. Fortunately, Germany has a strong infrastructure with rare disease centers established over a decade ago. However, the referral patterns to these centers could be more effective. In addition, some countries have better patient registries, gathering valuable data on the natural progression of rare diseases. The National Registry for Rare Diseases (NARSE), an initiative by the Eva and Horst Köhler Foundation for a unified registry across multiple rare diseases, could be a major improvement by helping generate real-world evidence, especially in areas where natural history data is limited. This could be valuable also for determining the value of therapeutic innovation.
EF: Do you have a strategy set in place from your frontline to raise awareness on rare diseases and be a part of the collective data that can give you a more standardized way of care, therefore making it easier for you to bring these innovative therapies to be more accessible?
RS: We educate physicians who may encounter rare disease patients, helping them recognize red flags. While we don't expect these doctors to manage treatment, we aim to enable them to refer potential cases to specialized centers where diagnoses can be confirmed and treatment initiated. It's unrealistic to expect GPs and pediatricians to know the thousands of rare diseases they might rarely, if ever, encounter in their careers. We also reactively support screening initiatives and diagnosis, particularly in countries where genetic testing is not generally reimbursed. In areas of our primary interest, we work closely with professional societies and experts to expand available clinical and scientific evidence and participate (alone or together with other companies) in establishing or supporting educational and disease awareness programs. For the same purpose, we also partner with many Patient Advocacy organizations in individual European countries as well as with multinational associations.
EF: If you were to address any collaborations in the future, what are the main priorities for rare diseases in the DACH region overall, what would be your message to other collaborators, and what do we need to align on to move forward innovation for rare diseases?
RS: Despite efforts from the scientific community, patient advocacy groups and industry, many rare diseases remain underdiagnosed and undertreated. Because of the complexity of our healthcare systems, bringing stakeholders together can be eye-opening and mutually beneficial. Over the past year, I've spoken with many individual payers and health insurers to better understand their challenges. Their predicament is that the government makes promises that cost sick funds extra money, leaving statutory health insurance with no other choice than to raise extra premiums, which damages their competitive position and their reputation. It would benefit patients and payers if we address inefficiencies in the healthcare system to liberate resources that patients with rare diseases need. Market access remains a major challenge, and I wonder how this will change next year when the Joint Clinical Assessment on a European level enters into effect for ATMPs. It might improve access if real-world evidence is recognized more often than currently in Germany. The JCA may also accelerate access in countries that do currently not maintain an HTA, which would be welcome, but the JCA will not replace current HTA processes in Germany and other countries. Instead, it adds another bureaucratic layer and extra costs. We need to learn from experience with this new regulation and jointly flag anything that does not serve the interests of patients. The EU pharmaceutical strategy that was announced in 2023 defined ambitious goals for faster market access but also wanted to improve the competitiveness of the industry in Europe. I hope that this time, the EU will be more successful than it was with the Lisbon agenda of 2001. Not many people remember, but the goal was to make Europe the world’s most competitive economic region - a goal that was clearly missed. I’m skeptical about more regulations that add to, rather than replace, existing procedures. I would like to see the system evolve as we gain experience, especially as the first ATMPs go through this process next year, as I see a general need for more flexibility to account for the broad spectrum of different rare diseases. Since the inception of AMNOG, around 50 drugs have exited the German market due to unsustainable pricing. Beyond those that exited, additional drugs were never launched at all, and the government has recognized that the strict pricing guardrails imposed by the Act on the Stabilization of Statutory Health Insurances Financing (GKVFinStG) made things worse by limiting access to innovative treatments. This could put Germany behind other countries in terms of therapeutic standards. The JCA may help prevent cases where HTAs in different countries reach opposite conclusions based on the same scientific evidence. For example, while the GBA in Germany ruled that one of our drugs had no advantage over its comparator, the French Haute Autorité de Santé issued a positive verdict with an ASMR rating of three. It's surprising to see HTA bodies coming to very different conclusions when analyzing the same medical evidence, and very unfortunate for the patients in Germany, particularly when minor of age. We've been in close talks with payers, who understand the situation but are constrained by the system's rigid rules. Greater flexibility in the system would allow us to reach adaptable agreements with payers, acknowledging the specific needs of individual patients affected by rare diseases.
EF: What do you look forward to seeing in 2025 when celebrating the past 15 years since Ultragenyx’s establishment? What do you hope to achieve next year, and what is your outlook for the future of Ultragenyx as a company beyond Germany?
RS: Ultragenyx is a phenomenal success story – we have developed meaningful innovations for patients in a very short time and we’re only just getting started. My hope is that our success in R&D continues and that we will be able to successfully commercialize our innovations to then fund the development of more new treatments in more indications with high unmet needs. I am a strong supporter of emerging markets, so I hope that Ultragenyx will be able to expand into more geographies, though political instability can make this challenging. I also hope that the positive shift in biotech financing continues, with more investors showing interest in our industry. Biotech relies on venture capital, as the majority of innovation in rare diseases comes from small companies. This is an area where Europe is lagging far behind the USA. Europe has excellent researchers, but we need to be more effective in financing start-ups. In Germany, the new Medical Research Act, which is about to enter into effect, introduces confidential pricing options for companies under certain conditions. Though it includes an additional 9% slashed off the negotiated price, having this option—a standard in most European markets—is a big step forward. While some aspects of what the law meant to foster research seem unclear, confidential pricing marks real progress, a shift championed by Dr. Karl Lauterbach, the current Health Minister. Interestingly, as a member of the Socialist Party, Dr. Lauterbach has shown courage in addressing issues like excessive hospital spending and Germany’s high number of hospital beds per capita despite likely resistance. I greatly respect his determination and hope that the recent demise of the German government will not put an end to much-needed reforms. In Austria, a new procedure introduces a nationwide committee to assess the benefits of hospital products (Bewertungsbords). Austria's healthcare system is more flexible than Germany's, which fosters innovation. If implemented well, Austria could continue as an early launch country with efficient pathways for rapid innovation. However, there is some concern that the Bewertungsbords might slow things down and create a new hurdle to access, but we’ll have to see as the first products go through the process. It is still unclear which products will be evaluated, likely only those with significant impacts on hospital budgets. Being outside the EU, Switzerland has a separate regulatory pathway and particularly high market entry costs, which has deterred some small companies with limited resources from registering products with Swissmedic. Switzerland has a good system for assessing individual reimbursement requests from physicians, ensuring consistent evaluations based on evidence, unmet medical needs, and treatment effectiveness. New regulations that deteriorate Named Patient access do not serve patients’ interests.
EF: Do you have a final message for your team as Ultragenyx reaches 15 years this April?
RS: I've been with Ultragenyx Germany for eight years. This company is truly unique, and in my time here, I’ve seen remarkable leaders guide us forward. While our headquarters are in California, we also have multiple locations in the Boston area, including our gene therapy manufacturing facility, which are both very competitive labor markets where you’d expect some turnover. Yet, not only is our turnover remarkably low, but Ultragenyx is more than its people; the shared spirit of changing the future of rare disease medicine globally remains strong. It may sound ambitious, but we're serious about putting patients and their needs first, going further than individual products. There's much more we can and will achieve in the future. We are developing groundbreaking therapies for more rare diseases and working to make them available in more and more countries by expanding our geographic footprint in EMEA – already, we have a presence in more than 20 countries, either maintaining our own operations or working with partners.
