New Medicines

UpstazaAromatic L-amino acid decarboxylase (AADC) deficiency


New molecular entity
PTC Therapeutics
PTC Therapeutics

Development and Regulatory status

Aug 22First patient has been treated with Upstaza after being approved for use in Europe [16].
Jul 22Approved in the EU. PTC says it is ready to deliver Upstaza to patients as soon as possible [15].
May 22Recommended for EU approval under exceptional circumstances by CHMP for “the treatment of patients aged 18 months and older with a clinical, molecular, and genetically confirmed diagnosis of aromatic L‑amino acid decarboxylase (AADC) deficiency with a severe phenotype”. Upstaza will be available as a 2.8 x 1011 vector genomes/0.5 mL solution for infusion [14].
Apr 22CHMP decision now expected in May [13].
Feb 22An opinion on the MAA for PTC-AADC is expected in April 2022 from the EMA CHMP, and PTC now plans to file to the US FDA in Q2 22 [12].
Nov 21At its November meeting, the EMA CHMP endorsed a 2nd list of outstanding issues with a specific timetable, as adopted by Committee for Advanced Therapies (CAT). The CHMP noted that the CAT had agreed to consult a Scientific Advisory Group with a list of questions [11].
Oct 21PTC expects to receive a CHMP opinion Q4 2021, and will file to the FDA in Q1 22 [10].
May 21EMA Committee for Medicinal Products for Human Use (CHMP) requests a clock stop for to allow for completion of its assessment of eladocagene, including its pre-approval inspections. PTC Therapeutics also reports a delay in the submission of biologics license application (BLA) by at least one quarter for the treatment of AADC deficiency to the US FDA due to COVID-related surgical delays [9].
Oct 20PTC Therapeutics expects the CHMP opinion for AADC deficiency in H1 21, and to submit a BLA to the US FDA also in H1 21 [8].
Jan 20Filed in EU for treatment of AADC deficiency [7].
Oct 19PTC Therapeutics started preparing a license application for the treatment of AADC deficiency for submission to the US FDA in the fourth quarter of 2019 [5]
Aug 19PTC are preparing for US filing of eladocagene exuparvovec, and have leased a new site to support AADC gene therapy production. They will work on release of the first commercial batch and anticipate FDA submission with the completion of manufacturing this year [4].
Jan 19Company plans to file in EU & US in H2 19 [3].
Jan 19Has Rare Paediatric Disease designation in the US [3].
Jan 19Has orphan drug status in EU & US [3].
Dec 18Based on FDA input and feedback from EMA, PTC Therapeutics does not deem necessary and do not plan to conduct a PIII trial for eladocagene exuparvovec for the treatment of AADC deficiency [3].


An in vivo gene therapy using an adeno-associated virus 2 (AAV2) vector to deliver the gene for human aromatic L-amino acid decarboxylase (hAADC) to nerve cells where it corrects the defect, increasing AADC and neurotransmitters, e.g. dopamine, serotonin.
A very rare, severe, genetic neurometabolic disorder associated with clinical manifestations related to underproduction of serotonin and dopamine, mainly hypotonia, hypokinesia, ptosis oculogyric crises, and signs of autonomic dysfunction. Prevalence is <1 in 1 million [1].
Aromatic L-amino acid decarboxylase (AADC) deficiency

Further information


Trial or other data

Dec 19No UK trial sites [6]
Oct 19Combined results from 18 patients with severe AADC deficiency ranging from 21 months to 8.5 years of age, each of whom received a single administration of AGIL-AADC at a dose of 1.8x10e11 vg total delivered to the putamen. At baseline, patients had no functional movement and failed to achieve any motor milestones, including head control, sitting or standing capabilities. Compared to baseline at one-year and at five-years after AGIL-AADC administration, patients had objective evidence of de novo dopamine production as visualized by F-DOPA PET imaging of the brain, consistent with successful and stable DDC gene transduction over time. After administration of AGIL-AADC, the combined group of patients showed significant change from baseline capabilities at one-year post-treatment in functional motor skills assessed with the Peabody Developmental Motor Scale, Second Edition (PDMS-2) total score (p<0.00001) as well as locomotion, grasping, visual-motor integration and stationary subscales (all p<0.00001). Similar changes from baseline at one-year post-treatment were also observed for the combined group of patients on the Alberta Infant Motor Scale (AIMS) total score (p<0.0001) and prone, supine and sit subscales (all p<0.0001) and the stand subscale (p=0.003). Patients showed statistically significant improvements at both two- and five-years post-treatment in achievement of motor milestones of full head control (p<0.0001 at two and five years), sitting unassisted (p=0.0004 at two years; p<0.0001 at five years) and standing with support (p=0.005 at five years), reinforcing the clinical benefit and sustainability of functional motor improvements. The PDMS-2 and AIMS are validated scales used to assess motor skills in young children [5].
Dec 16PI/II study (NCT01395641) completes [3].
Sep 16PII expansion trial, to extend the eladocagene exuparvovec gene therapy to children with AADC deficiency, who were not enrolled into the previous PI/II trial starts (NTUH-AADC-011; NCT02926066). The open-label trial will enrol approximately 10 patients of 2-6 years of age, in Taiwan [3].
Oct 14PI/II study to evaluate the safety and efficacy of eladocagene exuparvovec gene therapy in patients with AADC deficiency starts (NCT01395641; NTUH-AADC010). Ten patients aged at least 24 months will be enrolled in Taiwan. Primary outcome measures are measurable neurotransmitter metabolite HVA or HIAA levels in CSF one year after gene therapy, and increase of PDMS-II score more than 10 points one year after gene therapy. Collection of these data is due to complete Dec 20 [2].

Evidence based evaluations