PYC: First patient to receive ADOA medication in October 2024
At the end of September, we had a joint meeting with PYC and with the Autosomal Dominant Optic Atrophy Association, our sister organization from the US. PYC has been working for some time on a treatment for classic ADOA, where the OPA1 mutation causes the disease and there are no symptoms other than loss of vision. In classic ADOA, a deficiency of OPA1 leads to damage to the mitochondria, which eventually leads to the death of the mitochondria in the retinal ganglion cells (RGCs). RGCs cannot function without mitochondria in the cell, which causes the RGCs to slowly die. This causes a reduced density of the optic nerve, which in turn leads to loss of vision, usually over a longer period of time. PYC is currently focusing on this simplest variant (the so-called haplo-insufficient patients), excluding patients with a dominant negative mutation (where the OPA1 mutation has additional toxic effects) and patients with additional symptoms such as ADOA+.
BANKSIA
PYC is currently conducting a natural history study called BANKSIA. The aim is to understand the progression of ADOA and to demonstrate biological changes (biomarkers) that are associated with the progression of the disease. Although ADOA ultimately leads to vision loss, mitochondrial damage occurs much earlier. However, measuring mitochondrial damage is difficult.
The BANKSIA study is investigating two innovative biomarkers – Retinal Apoptotic Cell Detection (DARC) and Flavoprotein Fluorescence (FPF) – to assess the progression of ADOA at the molecular level. These biomarkers are important because clinical trials may not be able to directly demonstrate improvement in vision (the loss of vision is too slow). Therefore, PYC aims to determine whether the decline in these biomarkers is related to decreased optic nerve density, the last step before vision loss. This study will provide crucial insights into the progression of the disease.
The natural history study, BANKSIA, is actively enrolling participants and will last 24 months. The study will enroll 40 patients >8 years old and follow their progress at multiple time points.
SUNDEW
In addition, PYC is also testing a new drug for ADOA in a study called SUNDEW. The SUNDEW study is looking at the safety and pharmacokinetics (how the drug is absorbed in the body) of PYC's ADOA drug candidate, PYC-001.
SUNDEW is a single ascending dose (SAD) clinical trial that will begin in Australia. A so-called open-label phase 1 study will enroll patients aged 18 years and older, who will receive a single eye injection, followed by a four-week monitoring period. PYC hopes to detect early changes in the DARC and FPF biomarkers. This will inform future studies in patients with more severe forms of ADOA.
The researchers also plan to propose a composite endpoint for approval of their pivotal trials, to increase the likelihood that efficacy will be demonstrated within the study's time frame.
The SUNDEW study is mainly taking place in Australia (Sydney and Tasmania). There are plans to expand to the United States.
The SUNDEW study has not yet recruited enough patients. This is because initially only patients with a certain visual acuity were allowed to participate. In response, PYC has adjusted the study protocol. The inclusion criteria have been relaxed. Now people are eligible based on visual field testing, allowing more patients to participate. Furthermore, PYC is open to working with patient organizations such as the Cure ADOA Foundation and ADOAA to increase awareness and recruitment efforts. We have discussed recruitment and expansion of sites and Cure ADOA and ADOAA have offered their help in reaching Australian patients.
If this initial single-dose trial proves safe, an additional safety study will follow, where patients receive the drug multiple times to test long-term safety (MAD). If that study is successful, PYC plans to launch larger pivotal trials to show that the drug really works.
This is very important for the agencies that assess the safety of the drugs, such as the EMA or FDA. Only after their approval can the drugs be sold. It is also important for reimbursement by health insurers or health systems such as the NHS, and for prescribing doctors. If all goes well, patients could receive this drug from their ophthalmologists in the early 2030s.
How can I participate?
Clinical trials are therefore necessary to bring new drugs to the clinic in the future and to enable reimbursement by health systems or insurance companies. PYC is currently conducting a series of studies in Australia, France, the Netherlands, Germany, Austria and at various locations in the US, including Florida and Washington. These studies can only be successful if sufficient patients participate.
Therefore, such studies require committed volunteers who are willing to dedicate their time and expose themselves to the discomfort of multiple tests/medical procedures. In return, all costs related to flights, local transportation, accommodation, etc. will be fully covered by PYC. Both for the participants and their traveling companions. PYC is committed to making this process as smooth and accessible as possible for those participating in the trial.
If you are seriously interested in participating in the natural history study, please click on one of the following links for more information:
Dutch https://adoa.eu/nieuws/meld-je-aan-voor-onderzoek-pyc
English https://adoa.eu/en/news/sign-up-for-pyc-research
German https://adoa.eu/de/nieuws/meld-je-aan-voor-onderzoek-pyc
Information about the reflective study – Banksia (PYC-001) https://clinicaltrials.gov/study/NCT06140329
Information about the drug study – Sundew (PYC-001-101) https://clinicaltrials.gov/study/NCT06461286
