Novartis AG announced, via Syncona Ltd, that it will discontinue the clinical development of the gene therapy GT005, indicated for the potential treatment of geographic atrophy (GA) secondary to dry age-related macular degeneration (AMD).
Let’s start with some background.
Novartis purchased London-based Gyroscope Holdings Limited Ltd. (the original developer of GT005) from Syncona—a large, closed-ended, healthcare investment company—in February 2022.
The deal included an upfront cash payment of $442 million to acquire Gyroscope, as well as a total upfront cash consideration for $800 million.
A series of milestone payments were also in consideration for Syncona, pending a successful clinical development and commercialization of GT005.
How much more would that have totaled?
Per Syncona, the payments would have been valued at $68.1 million.
What happens now?
According to Syncona, the payments will be written off, resulting in a negative valuation impact.
Now talk about GT005.
GT005 was designed as an adeno-associated vector (AAV)2-based, investigational gene therapy that sought to restore balance to an overactive complement system via increasing complement factor I (CFI) protein production.
The thought was that an increase in CFI production could lead to reduced inflammation and, as a result, preservation of a patient’s vision.
How far in the clinical process did it get?
The gene therapy had already received Fast Track Designation from the FDA.
Trial-wise, it was undergoing evaluations in a phase 1/2 and two phase 2 clinical trials.
So why discontinue?
Per Novartis, the decision was based on a recommendation from an overall benefit risk assessment of available data from the asset’s program studies conducted by the independent Data Monitoring Committee (DMC).
Of note, the DMC works with investigators and sponsors to monitor trial conduct and safety, assess risks and benefits, and to make recommendations to protect trial participants.
In this case, the DMC had concluded that futility criteria had been met, and no new safety signals were identified.
Explain futility criteria.
Per the FDA, clinical trials and investigational assets may be stopped for futility if there is little or no chance that the asset will demonstrate its intended effect (treatment of GA secondary to dry AMD, for GT005).
Such reasons include:
- Evidence of no treatment effect
- Substantial missing data that would undermine trial conclusions
- Rates too low to support meaningful comparisons.
Any input from Novartis on this?
The company released a statement on the discontinuation, stating, “We are committed to ensure patients treated with [GT005] are provided with long-term safety follow up.”
Novatis also added that it will be sharing its clinical data from the early studies on GT005 with both the ophthalmology and science communities in support of future gene therapy developments.