Development of Rare Disease Therapies: Overcoming Challenges

Quick Overview

In this talk, Emil Kakkis discusses the challenges faced in the development of rare disease therapies. He shares his own experiences in developing enzyme therapies and gene therapies for various rare diseases. Kakkis emphasizes the importance of perseverance and problem-solving in overcoming obstacles throughout the drug development process. He also highlights the need for patient-focused approaches and ensuring access to treatments. Kakkis provides examples of challenges faced in clinical trials, manufacturing, and regulatory processes. He concludes by discussing the ongoing development of GTX-102 for Angelman syndrome and the potential for transformative treatments in rare diseases.


In this talk, I will discuss the development of rare disease therapies and the challenges that come with it. While there is exciting progress in the field of rare disease science, it is important to recognize that the journey from initial research to approval is a long and difficult battle. I will share some of my own experiences and highlight the importance of perseverance in overcoming these challenges.

The Journey from Research to Approval

Academic Beginnings

My own journey in rare disease therapies started as an academic professor. I developed an enzyme therapy that showed promising results in treating dogs. However, the path to human trials and approval was filled with obstacles. It required significant funding, involvement of hundreds of people, and millions of dollars. Despite the challenges, the therapy eventually received approval, demonstrating that it is possible to overcome the hurdles in the development process.

Establishing Ultragenyx

In 2010, I founded Ultragenyx with a small team and a few million dollars of my own funds. Our focus was on serious metabolic disorders, and over the years, we have raised billions of dollars and expanded our team to over 1,100 employees. We are now working on treatments for 20 different rare diseases, aiming to provide the first-ever therapies for these conditions.

Mission and Challenges

Treating as Many Rare Genetic Diseases as Possible

Our mission at Ultragenyx is to treat as many rare genetic diseases as possible. With advancements in technology, there are numerous ways to move forward in this field. We have developed a high-quality team that works efficiently to achieve this goal. Patient focus is a key aspect of our mission, and we are committed to ensuring access to our treatments for patients in the U.S., regardless of their financial situation.

Balancing Business and Finances

While our primary focus is on the science and patient care, we also need to be smart in managing the business and finances. Developing rare disease therapies is an expensive endeavor, and we must find ways to make the money work efficiently. By working smart and fast, we can maximize our impact and help as many patients as possible.

Filing for Approval: What It Takes

Filing for approval of a rare disease drug is a complex and detailed process. To provide some insight into this, I will share the example of UX003, an enzyme therapy for MPS VII. The filing for approval in the U.S. consisted of 76,000 pages and 1,100 individual documents. Similarly, the more recent approval for UX007 involved 228,000 pages and 1,700 documents. These filings require an incredible amount of detail and meticulousness.

Examples of Challenges and Solutions

Overcoming Theoretical Concerns

In the development of enzyme therapy for brain-related diseases, we faced skepticism about the effectiveness of delivering the therapy through the spinal fluid. However, we proved that it could work and successfully treated patients in Europe when the FDA had theoretical concerns. This highlights the need to challenge assumptions and find alternative paths to move forward.

Managing Allergic Reactions

In the clinical trial for Aldurazyme, we encountered concerns about potential allergic reactions. When a severe reaction occurred in one patient, it created doubt and fear among the parents of other patients. However, through careful analysis and adjustments in administration, we managed to address the issue and continue the trial successfully. This demonstrates the importance of perseverance and problem-solving in the face of challenges.

Manufacturing Difficulties

Manufacturing rare disease drugs can be incredibly challenging and expensive. For example, Naglazyme, an enzyme therapy, was initially dropped by two companies due to manufacturing difficulties. However, through perseverance and incremental improvements, we were able to make it stable and approved for use in treating thousands of patients. This highlights the need to find innovative solutions and overcome manufacturing obstacles.

Safety Concerns and Regulatory Delays

In the development of GTX-102, we encountered safety concerns related to lower extremity weakness. While the data indicated that the effect was localized and manageable, the FDA took a conservative stance, leading to delays in the approval process. To move forward, we opened up sites outside the U.S. and continued discussions with the FDA. Despite the challenges, we remain committed to finding a solution and providing the treatment to patients.


The development of rare disease therapies is a challenging journey that requires perseverance, adaptability, and a patient-focused approach. While obstacles and setbacks are inevitable, it is important to remain dedicated to the science, respond to data, and manage regulatory requirements. By working together and pushing forward, we can overcome these challenges and provide life-changing treatments for rare genetic diseases.

Talk details

  • Title: Development of Rare Disease Therapies: Overcoming Challenges
  • Author(s): Emil Kakkis
  • Author(s)’ affiliation: Ultragenyx Pharmaceutical
  • Publication date: 2022-01-04
  • Collection: 2021 FAST Science Summit