FDA fast-tracks Sanofi's gene therapy for eye disease GA

Sanofi has been granted a speedy review from the FDA for a gene therapy for geographic atrophy (GA), a complication of age-related macular degeneration (AMD), as it prepares to test it in a clinical trial.

The SAR446597 gene therapy could provide a one-off treatment for GA, a major cause of irreversible sight loss that affects millions of people around the world, and free patients from the need for injections into the eye every few weeks using current therapies.

The newly awarded fast-track status is reserved for new drugs and vaccines that aim to treat or prevent serious conditions, for which there are few or no alternative therapies, and can speed up their development and review, getting them to patients more quickly.

According to Sanofi, SAR446597 delivers genetic material encoding two therapeutic antibody fragments that target and inhibit two components of the complement pathway, namely C1s in the classical pathway and factor Bb in the alternative pathway.

The company said this dual approach delivers "sustained complement suppression within the retinal microenvironment." The complement immune system is thought to be over-activated in GA.

It is preparing to start a phase 1/2 trial of the gene therapy, its second in the retinal diseases area after SAR402663, another one-shot gene therapy for neovascular or 'wet' AMD, which started a phase 1/2 study last November.

AMD is an acquired progressive degeneration of the retina that affects approximately 200 million people globally, said Sanofi. GA is an advanced form of dry AMD, which results when the central part of the retina starts to deteriorate, while wet AMD is caused by the growth of aberrant blood vessels in the retina.

Sanofi was formerly working with UK biotech Gyroscope Therapeutics on gene therapies for AMD, taking an option on its lead candidate for GA – GT005 – in 2021 in a deal that included an upfront payment of $40 million.

That came to an end after Novartis acquired Gyroscope later that year in a deal valued at up to $1.5 billion, taking control of the programme, which was in a pair of phase 2 studies. Two years later, Novartis abandoned GT005 – which delivered the gene coding for complement factor I (CFI) – after interim results from the studies suggested there was little chance of showing efficacy.

Other companies developing gene therapies for GA include Johnson & Johnson, which licensed rights to a candidate from Hemera Biosciences in 2020 (JNJ-1887) that expresses a soluble form of CD59 and is now in phase 2 testing.