Novartis drops geographic atrophy gene therapy

Novartis has confirmed it will discontinue development of a gene therapy for sight-robbing disease geographic atrophy (GA) two years after acquiring its UK-based developer.

The GT005 (PPY988) gene therapy, originally developed by Gyroscope Therapeutics, was in several phase 2 studies as a one-off subretinal injection in subjects with GA secondary to the drug form of age-related macular degeneration (AMD), a leading cause of blindness.

GT005 aimed to treat GA by delivering the gene for complement factor I (CFI) to the eye using an adeno-associated virus (AAV) vector. CFI regulates the activity of the complement immune system, which is over-activated in GA, leading to the degeneration of cells in the central portion of the retina.

In a statement, Novartis said it had decided to abandon the programme based on a recommendation from the independent data monitoring Committee (DMC), which concluded it was futile to continue the studies based on "an overall benefit-risk assessment of available data."

It stressed that no new safety signals were found, but said that, while the studies have been halted, patients already treated with GT005 will be followed up to monitor for side effects.

"Our disappointment in this outcome is first and foremost for the GA community," said Novartis, which had been hoping that GT005 could become an effective one-shot therapy for a disease that affects around eight million people globally.

Novartis bought Gyroscope in 2021 for $800 million upfront, with another $700 million owing if GT005 met its objectives on clinical development, regulatory approvals and reimbursement.

Since that takeover, the first treatments to treat GA have reached the market. Earlier this year, Apellis Pharma got FDA approval for Syfovre (pegcetacoplan), a complement C3 inhibitor, and that was followed by a green light for Astellas/Iveric Bio's complement C5 inhibitor Izervay (avacincaptad pegol).

Both need to be given as an intravitreal injection into the eye every few weeks, and there is still hope that a one-off gene therapy could reduce that treatment burden for patients.

Novartis has a possible backup position in GA, stemming from its $280 million takeover of US start-up Vedere Bio in 2020, although it seems that hasn't moved beyond preclinical development as GT005 is the only clinical-stage GA programme listed in the drugmaker's pipeline.

Also working on a gene therapy for GA is Johnson & Johnson, which has a candidate called JNJ-1887 in phase 2b, while Roche has taken a slightly different approach with its cell-based therapy RG6501 in mid-stage trials.

JNJ-1887 is designed to increase the expression in the eye of a soluble form of CD59 intended to protect retinal cells from degenerating, while RG6501 – originally developed by OpRegen – is based on retinal pigment epithelial (RPE) cells.