PTC-AADC Gene Therapy’s European Approval Process Moves Forward

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by Lindsey Shapiro, PhD |

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A European Medicines Agency committee is expected to provide an assessment of PTC-AADC (eladocagene exuparvovec) gene therapy for treating aromatic l-amino acid decarboxylase (AADC) deficiency this month, which will inform the final decision about whether the treatment will receive marketing approval in Europe.

The therapy’s developer, PTC Therapeutics, announced that it has completed meetings with the Committee for Advanced Therapies, which will now generate a report about PTC-AADC’s quality, safety and effectiveness.

That opinion will be sent to the Committee for Medicinal Products for Human Use, which will then make a final recommendation about approval to the European Commission.

“We are looking forward to treating patients with our gene therapy treatment for AADC deficiency,” Stuart W. Peltz, PhD, PTC’s CEO, said in a press release. “AADC deficiency is such a terrible disease and we believe that this treatment has the potential to be transformational for patients with this disorder.”

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Motor Symptoms Impact Patient, Caregiver Life Quality, Study Finds

AADC deficiency is a very rare disease caused by mutations in the DDC gene, which leads to a deficiency in producing its protein, AADC.

AADC is an enzyme critical for producing multiple neurotransmitters — chemicals that nerve cells used to communicate — and its deficiency leads to low neurotransmitter production and hindered nerve cell function. Children with AADC deficiency are often delayed or fail to reach developmental milestones like walking or talking.

Administered via a one-time infusion directly into the brain, PTC-AADC uses a viral carrier to deliver a healthy copy of DDC to the body’s cells, allowing them to produce their own AADC, and in turn, restore neurotransmitter levels.

The procedure specifically targets infusion to a brain region called the putamen, which normally produces a large amount of the neurotransmitter dopamine, and is particularly impacted by AADC deficiency.

According to the company, the surgical approach required for the treatment’s delivery is minimally invasive and has proven to be safe in children and adults with neurological disorders.

PTC’s application for marketing approval in Europe was supported by the findings from three open-label clinical studies conducted in Taiwan — a Phase 1/2 trial (NCT01395641), a Phase 2b trial (NCT02926066), and a compassionate use study, which provided the treatment to very ill patients with no medical alternative.

Long-term results from these trials, which treated 26 children overall, showed the therapy was generally safe and well tolerated and led to sustained motor and cognitive improvements up to five years after the infusion.

The treatment enabled a few of the children to be able to walk freely and one child to be able to talk a few years after receiving it.

Data showed that a younger age at the time of treatment was significantly associated with greater and faster motor symptom improvements in the children.

Children in these studies also saw healthy weight gains and improvements in other symptoms, including bad mood, excessive sweating, an inability to control temperature, and oculogyric crises — a common eye movement disorder in AADC deficient patients.

Imaging studies showed increased AADC activity in the putamen, indicating the treatment was working as intended.

Most of the children (24) experienced dyskinesia, or involuntary movements, that are a common side effect of therapies that increase dopamine levels. These were more severe in older children and generally resolved within 10 months after the infusion. Most children also developed transient immune responses against the treatment’s viral carrier, a common problem for gene therapies.

PTC’s application was also supported by data from two patients in Europe who received the therapy under a compassionate use program, the company reported.

If  the gene therapy is approved, it will be the first one marketed that is directly infused into the brain, PTC reported.