Adelaide-based Nova Eye Medical says it has navigated a time-consuming and complex series of conversations with the US Food and Drug Administration (FDA) to pave a clear approval pathway for its pioneering 2RT laser system for selected intermediate age-related macular degeneration (iAMD) patients.
Melbourne’s Professor Robyn Guymer will lead the important study to build on findings in the seminal LEAD trial, which she described as very encouraging, but not conclusive.
The ASX-listed company announced on 3 May the clinical study plan and the commercial rights would be pursued by its subsidiary AlphaRET. 2RT is described as a world first nanosecond laser therapy to treat iAMD, which works by stimulating the rejuvenation of retinal cells to initiate a healing response targeting the underlying causes of AMD.
“As we pioneer this novel ground-breaking therapy using 2RT to transform the treatment of intermediate iAMD, we acknowledge that the dialogue with the FDA has been time-consuming. It has also been complex,” Nova Eye Medical managing director Mr Tom Spurling said.
“We believe that the extent of the dialogue with the FDA demonstrates the potential importance of 2RT and it is a very positive achievement to have now established a clear path forward.”
The company stated that current treatment options for iAMD patients are limited, with nutrient supplements a possible option. Once disease progresses to later forms such as neovascular AMD, patients often require regular anti-VEGF intravitreal injections.
However, in late 2018, 2RT was shown to reduce progression of iAMD in a key subgroup of patients. This was demonstrated in the LEAD study published by the Centre for Eye Research Australia’s Professor Guymer et al in the peer-reviewed American Academy of Ophthalmology journal Ophthalmology.
The trial was hailed as the first time a laser intervention had been shown to reduce the rate of disease progression in selected patients with iAMD.
But at the time, the trial was met with a mixed response after it missed its primary end point before a post-hoc analysis later showed 2RT’s treatment effect was significant, but only in a subset of patients without reticular pseudodrusen (RPD), a fatty deposit that is associated with the later stages of AMD.
Previously, the relevance of RPD in the pathology of AMD was not well understood, and so it wasn’t accounted for in the LEAD trial design. Specifically, the post hoc analyses showed that in patients who did not have co-existent RPD, 2RT resulted in a clinically meaningful 77% reduction in the rate of disease progression at 36 months following treatment.
Therapy could alter AMD landscape
AlphaRET’s recent communications with the FDA has provided guidance on the regulatory pathway for approval of 2RT in the US for select patients with iAMD.
Based on the FDA feedback, AlphaRET will begin a confirmatory pivotal clinical study outside of the US at sites in Australia, Canada and Europe. The principal investigator will be Prof Guymer, with early data then to be submitted to the FDA. Importantly, the FDA has agreed that patients with RPD will be excluded as they seek to confirm the findings of the LEAD Study key subgroup analysis.
The company expects this will enable the expansion of investigator sites into the US and the progression of the pivotal clinical study for US marketing clearance.
“I am pleased to be a part of this follow up study. 2RT addresses the disease in its earlier stages. No other device or pharmaceutical in the world does this,” Guymer said.
“Like all chronic disease, early detection and treatment is vital to prevent complications and the ensuing burden on healthcare systems, and patients and their families. The LEAD study was very encouraging but was not conclusive. I look forward to starting this work, providing additional information to the FDA and then a successful study outcome.”
Dr Philip Rosenfeld, Professor of Ophthalmology at the Bascom Palmer Eye Institute of the University of Miami Miller School of Medicine in Miami, pioneered the use of the anti-VEGF therapy Avastin in nAMD. He is also an advisor to AlphaRET.
“The LEAD Study completed by Professor Guymer was a well-controlled clinical trial that showed the immense potential of 2RT,” he said.
“However, a second study is required. If the second study is successful, AlphaRET will have the data needed to harness that potential and significantly change the landscape in AMD therapy in the USA and around the world. It is not unusual that the FDA is taking such a cautious approach and requesting additional data prior to establishing investigator sites in the USA. In fact, I am pleased that we now have a clear understanding of what is needed by the FDA to move 2RT forward in the USA.”