China as the "accelerator" for rare disease drug development: insights from Dr. Gianluca Pirozzi & AstraZeneca’s rare disease strategy
In the field of rare diseases, countless patients face the dual challenges of difficult diagnosis and limited treatment options. Dr. Gianluca Pirozzi, Senior Vice President and Head of Development, Regulatory, and Safety at Alexion Pharmaceuticals, AstraZeneca Rare Disease, is not only an industry expert deeply committed to this field but also the father of a child with a rare disease. Drawing from his personal experience and AstraZeneca's ongoing efforts, he sheds light on the challenges in rare disease R&D, potential breakthroughs, and the crucial role of China in this process.
At the 14th China Rare Disease Summit 2025, Dr. Gianluca Pirozzi addressed the theme of "Accelerating Rare Disease R&D Innovation," sharing insights on the current industry landscape, existing challenges, and AstraZeneca's practical initiatives.
The following content is organized by VCBeat based on the key points of his presentation:
With advancements in genetic sequencing and genomics technology, the number of identified rare diseases globally has increased from approximately 7,000 a few years ago to over 10,000 today, and continues to grow.
However, a concerning reality is that 90% of rare diseases still lack approved treatments. For instance, Amyotrophic Lateral Sclerosis (ALS) offers patients few effective therapeutic options, making the development of new drugs an urgent priority. Furthermore, 80% of rare diseases are genetic disorders, often manifesting in childhood. This adds complexity to pediatric drug development, as children's physiology differs from adults', requiring careful consideration in clinical trial design, dosage determination, and related aspects.
An even greater challenge for patients is obtaining an accurate diagnosis. The average global diagnostic journey for a rare disease lasts approximately 4.8 years, during which patients often experience misdiagnosis and consult multiple specialists. Even with Dr. Pirozzi's medical background, it took a year and a half for his daughter to receive a definitive diagnosis, highlighting the severe difficulties faced by families without medical expertise.
It is also important to note that definitions of rare diseases vary across countries and regions, typically based on patient population thresholds. The United States uses a threshold of approximately 200,000 affected individuals, China around 140,000 (unofficial definition), Japan 50,000, and Europe about 300,000. While these differences do not affect disease prevalence, they present challenges for global drug development collaboration and market access.
Core Challenges in Rare Disease R&D
From the preclinical stage, understanding of most rare diseases remains limited, and there is a lack of suitable animal models. Research on disease biomarkers is particularly challenging—without reliable models and biomarkers, verifying drug mechanisms and evaluating efficacy becomes difficult, directly hindering drug development.
During clinical trials, challenges persist: the small, scattered patient populations make subject recruitment difficult, and many rare diseases lack established clinical endpoints to measure progression. This necessitates close collaboration between pharmaceutical companies and medical experts to develop evaluation standards.
China offers unique advantages in patient recruitment. Through large medical institutions, it can consolidate patients from across the country, providing essential support for clinical trials and accelerating the development of rare disease treatments.
Additionally, regulatory frameworks for rare diseases require further refinement, with a need for more flexible policies. The United States has demonstrated regulatory flexibility through relevant legislation; China is also exploring streamlined approaches in regulations such as the Pharmaceutical Administration Law. This is vital for addressing global gaps in rare disease treatment.
AstraZeneca's Commitment to Rare Diseases
Dr. Gianluca Pirozzi stated that AstraZeneca remains dedicated to advancing treatments for rare diseases. With 30 years of experience in rare disease R&D, its products are now available in over 70 countries and regions globally. More than 5,000 employees worldwide are engaged in rare disease R&D efforts.
The company focuses on developing innovative drugs for diverse indications. Fifteen years ago, AstraZeneca introduced its first complement inhibitor—a pioneering therapy for Paroxysmal Nocturnal Hemoglobinuria (PNH), which significantly reduced five-year mortality rates. Since then, the drug has been expanded to indications including Atypical Hemolytic Uremic Syndrome (aHUS), Myasthenia Gravis (MG), and Neuromyelitis Optica Spectrum Disorder (NMOSD). A second-generation product has extended dosing intervals from bi-weekly to once every two months, greatly improving patient convenience.
Notably, AstraZeneca prioritizes early approval of rare disease drugs in China. With support from regulatory authorities, local R&D teams, and clinical experts, several drugs have been approved in China, covering multiple indications. For hypophosphatasia, AstraZeneca has a globally approved pediatric treatment and is developing regimens for adult patients, reinforcing its commitment to advancing care.
R&D Strategy: Patient-Centric Approach
Dr. Pirozzi emphasized AstraZeneca's patient-centric R&D strategy, focusing on three key aspects:
First, deeply listening to patients. In early R&D stages, patients and caregivers are invited to laboratories to discuss disease mechanisms and family burdens. Insights from families often reveal critical improvement indicators aligned with real-world needs, guiding R&D direction.
Second, designing patient-friendly clinical trials. Beyond consulting experts, AstraZeneca seeks input from patients and caregivers to assess trial feasibility. The team evaluates "patient friction coefficients," addressing challenges such as mobility issues, to simplify participation and enhance inclusivity.
Third, strengthening collaboration with patient organizations. Rare disease patient groups worldwide are key partners, helping identify eligible patients and facilitating communication with regulators—both crucial for rare disease R&D.
AstraZeneca's rare disease R&D focuses on five therapeutic areas: rare hematological and renal diseases, rare bone diseases, rare cardiomyopathies, rare amyloidosis, and the recently added field of rare oncology. While AstraZeneca has an established oncology R&D department, it aims to address gaps in rare cancer types, bringing hope to these patients.
Dr. Pirozzi reported steady progress in the R&D pipeline: advances in light-chain (AL) amyloid cardiomyopathy (Mayo IIIa/IIIb) and hypophosphatasia; expanded indications in the C5 field; approval in Japan for neurofibromatosis type 1 (NF-1) in adults, with reviews underway in the U.S., Europe, and China; and promising research in gene and cell therapies. These therapies offer curative potential—cell therapy for autoimmune diseases and gene therapy for rare diseases.
China's Role in Rare Disease R&D
Dr. Gianluca Pirozzi highlighted China's key role in advancing global rare disease treatment:
First, as a "drug development accelerator," China is a critical participant in Phase III trials. Rapid patient enrollment shortens global development timelines, and high-quality clinical data from China supports R&D reliability.
Second, as an "innovation frontier," China leads in Investigator-Initiated Trials (IITs) for cell and gene therapy. These innovative models accelerate drug development and attract investment, driving breakthroughs.
Third, as an "R&D incubator," China deepens disease understanding through national patient registries and large hospitals, enabling natural history studies, endpoint identification, and precise patient recruitment.
Data from China complements U.S. and European registries, providing a comprehensive disease view. AstraZeneca is collaborating with Chinese research hospitals to establish Rare Disease Centers of Excellence, focusing on rare renal and neurological diseases.
Finally, Dr. Pirozzi addressed a widely held concern: From a commercial and profitability perspective, rare disease patient populations are small and R&D costs are high—why does AstraZeneca remain committed to this area when many large pharmaceutical companies show limited interest?
His response was straightforward: because it delivers genuine value to patients. Many rare diseases carry high mortality and disability rates, yet effective therapies can fundamentally improve patient outcomes and reduce fatalities. The value of such treatments cannot be measured by patient numbers alone. For example, in treating atypical Hemolytic Uremic Syndrome (aHUS), our therapy has been shown to reduce mortality by 40–45%—this is the most direct demonstration of its value. Although the patient population is limited, combining reasonable pricing with the significant clinical benefits enables the development of a sustainable and profitable business model.
AstraZeneca has established a dedicated rare disease division covering a broad range of conditions, ensuring consistent investment to bring hope to more patients.