Novartis will discontinue development of GT005 gene therapy, a subretinal injection for geographic atrophy (GA), in a blow to the global macular disease community, including Australia where the therapy was being trialled in some hospitals.
The gene therapy, which was in Phase 2 trials, delivered the gene for complement factor I (CFI) to the eye using a viral vector. CFI regulates the complement pathway in the immune system, which is overactive in AMD, leading to degeneration of retinal cells.
The decision was based on recommendations by the independent Data Monitoring Committee (DMC), concluding that “futility criteria had been met”.
Novartis stated that no new safety signals had been identified and the company will conduct long-term safety monitoring for participants despite discontinuation of the studies.
GT005 was the focus of the HORIZON and EXPLORE trials which included trial sites in Australia, and was targeting GA secondary to dry age-related macular degeneration (AMD).
The Centre for Eye Research Australia’s principal investigator of retinal gene therapy research and vitreoretinal surgeon Dr Tom Edwards performed Australia’s first surgeries to administer GT005 to patients at The Royal Victorian Eye and Ear Hospital in Melbourne in 2021. The studies were aiming to recruit 20 participants at the time.
“Our disappointment in this outcome is first and foremost for the GA community,” Novartis said.
“We are subsequently communicating with study investigators, health authorities and relevant bodies and are committed to sharing information from these early studies with the ophthalmology and scientific communities to help inform future development of gene therapies. We sincerely thank the study participants and the investigators for their participation.”
Novartis procured the GT005 program after its acquisition of Gyroscope Holdings Limited from Syncona, a healthcare investment trust, in February 2022.
Syncona received an upfront payment of US$442 million (AU$ $685 m) from a total upfront cash consideration of US$800 million (AU$1.2 b) from Novartis. Syncona was also eligible for milestone payments subject to successful clinical development and commercialisation of GT005. However, the discontinuation of the trials has resulted in Syncona writing off £54.5 million (AU$103 m) in milestone payments.
“We are naturally disappointed for patients following the decision to discontinue GT005, but we respect Novartis’ decision,” Mr Chris Hollowood, CEO of Syncona Investment Management Limited, said.
“We remain focussed on our strategy of building and maintaining our portfolio of companies providing significant opportunities to deliver strong risk-adjusted returns to our shareholders and to make a difference to the lives of patients with devastating diseases.”
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