Upstaza Gene Therapy Results
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The Innovation of Upstaza Gene Therapy

In December 2018, my wife and I discovered our daughter had an ultra-rare disease known as aromatic l-amino decarboxylase (AADC) deficiency. It took time to fully understand this disease. What was apparent from the beginning was that there was no treatment. Until now.

I learned that AADC deficiency was a genetic disorder. When I heard “genetic disorder” my heart dropped because I equated genetics to meaning written in stone. But innovation in medical science has opened doors to new potential with the innovation of gene therapy.

The First Treatment For AADC Deficiency

Leading the innovation for AADC deficiency is Upstaza (eladocagene exuparvovec). Earlier this year, my wife and I offered a parent’s perspective of the drug to the European Medicines Agency (EMA). The EMA recommended approval of the gene therapy Upstaza to treat AADC deficiency in the European Union. Last month, we offered our perspective to the Medicines and Healthcare Products Regulatory Agency (MHRA). Again, Upstaza was granted approval in the U.K.

 Upstaza is the result of a decade of hard work, but gene therapy is only one factor that makes this therapeutic innovative.

The results of gene therapy are a miracle — like walking on water.

Walking on Water
Rylae-Ann and her dad explore low tide as they watch the sunrise.

Treatment Starts at 18 months Old

What makes Upstaza innovative is its ability to treat young children. It’s approved for patients 18 months and older. Our daughter was fortunate to receive treatment when she was 18 months old. It is one of the factors that her results have been so dramatic.

There are other experimental gene therapies, but they start treatment at older ages. This is still a huge opportunity, but the ability to treat at a younger age makes Upstaza stand out. As other alternatives become available, a key feature will be the age of treatment.

Clinical Trial Location

The clinical trial study took place in Taiwan, and for very good reasons. The population of AADC deficiency is around 130 patients, but Taiwan has the highest prevalence. By conducting the trial in Taiwan, they could successfully enroll a large number.

The clinical trial comes with some conditions to be eligible for the surgery. With an already limited pool of people, the criteria further limit the number of people who can participate. When you enroll in the trial, it is important families stay nearby. This is for safety and for collecting data.

Data was a significant consideration during our sharings with regulatory agencies. The purpose of a clinical trial is to collect data. Normally, a large population is required, but this is not possible for rare diseases. There is thankfully an alternative pathway for approval and requirements. However, data is still necessary so every person enrolled plays a substantial role in the data collected.

If the clinical trial was held anywhere else, there would be the added barrier of flying to the location, and an even harder commitment to continue to contribute the necessary data over years. Even in the Taiwan clinical trial study, we had to end her study early due to the COVID pandemic. The majority of families in the Taiwan clinical trial live in the small island country, so they could easily report back to submit data to investigators.

View from National Taiwan University Hospital
View from National Taiwan University Hospital looking out to the university campus and Taipei 101.

PTC Therapeutics Set The Example For Others

As others begin to complete the journey that PTC Therapeutics completed with Upstaza’s approval, they can learn from them. As alternatives begin their study, they will need to plan several years into the future. To make the process seamless and conclude with the same success, they now have a model to follow. As more competition enters, not only does the price drop but also more options become available and enhancements happen.

Clinical Trial Data Collection

The data collection process was thorough. It was difficult to subject our daughter to all the tests. She had high anxiety from the hospitals, and revisiting to have more tests did not help matters. We knew it was important that we contribute and continued to do so.

The problematic part was that we could not publicly talk about the trial. Also, we could not talk to each other. This created a difficult situation where we need the information to help provide better aftercare. In hindsight, we would have taken a different approach, but we stayed the course since it was essential for the investigators to collect valid and reliable data.

We could not make claims or share our success stories. One way this data collection was successful was that from our perspective that our daughter no longer has oculogyric crisis (OGCs). However, based on the doctor’s review our daughter did have OGCs because when she is tired and had a long day, she will have fleeting upward glances. The episode is completely different than before gene therapy and does not involve any muscles spasm. With the doctors setting the definition, we can have a consistent process of making valid claims about the effectiveness of gene therapy.

What Upstaza Means to AADCd Community

Approval of gene therapy means an approved treatment for AADC deficiency patients. It also has an effect on children not yet born.

Pharmaceutical companies see a pathway to investing in research and developing future therapeutics for rare diseases. The process is extremely difficult for the rare disease community, yet approval of Upstaza shows it’s possible.

Approval will encourage more innovation. PTC is already investigating using ClearPoint Neuro Navigation System to improve the delivery of gene therapy. Also, future studies may include gene therapy in vitro, robotic-assisted gene therapy, and cell therapy. Approval will create further innovation that we will continue to advocate for in the rare disease community.

Finally, researchers and institutions will explore rare diseases further. Gene therapy is not just a therapeutic for rare diseases. The innovation that happened in our community is sure to spread to more. Researchers and schools are taking notice. It is the future of medicine and we will need a team that is prepared to lead this future approach.