StemCell Therapy

LONDON Gyroscope Therapeutics Ltd. is poised to move the field of ocular gene therapy on from the treatment of inherited rare diseases to address more common eye conditions, after receiving FDA 510(k) clearance for its Orbit SDS subretinal delivery device.

Orbit SDS uses a cannula to deliver a therapeutic payload to the subretinal space, which it accesses via a suprachoroidal approach route. A microneedle inside the cannula enables targeted dose delivery.

That eliminates the need for a vitrectomy, and is both faster, easier and safer than the surgical procedure, removing concerns about gene therapy vectors leaking from the subretinal space.

Although vitrectomy has been used to deliver several gene therapies, it is not practical for treating hundreds of thousands of patients with dry age-related macular degeneration (AMD) and other common eye diseases. FDA 510(k) clearance of Orbit SDS now opens the way to scale up administration of ocular gene therapies to much larger indications.

The FDA clearance creates the potential to speed up development and widen patient access. In addition to a replacing a defective gene with a functional one, it will be possible to expand into the routine delivery of therapeutic proteins.

The company says it will use the device in its own clinical trials and make it available to other companies developing cell and gene therapies for eye diseases.

Charlotte Arnold, vie president of corporate affairs at Stevenage, U.K.-based Gyroscope told BioWorld the company now plans to integrate Orbit SDS into its GT005 program in dry AMD. We anticipate starting to generate data delivering GT005 using the Orbit SDS in a planned future cohort in the ongoing phase I/II Focus trial, she said.

Unlike the wet form of AMD that can be treated with anti-VEGF antibodies to prevent neovascularization, there is no therapy approved for dry AMD, which is both a cause of significant visual impairment and a precursor to wet AMD.

GT005 uses an adeno-associated virus to deliver the gene encoding an endogenous anti-inflammatory factor, to restore the balance of a complement system known to be hyperactivated in AMD. The aim is that a one-off treatment will prevent further degeneration.

The FDA nod is an important component of developing gene therapies to help preserve sight, said Khurem Farooq, CEO of Gyroscope. The Orbit [device] is exquisitely designed to target the subretinal space, with the aim of providing precise and consistent dosing, Farooq said.

The clearance for Orbit SDS rests on a phase IIb study of palucorcel (CNTO-2476), in the treatment of geographic atrophy of age-related AMD, an advanced stage of AMD, characterized by progressive loss of retinal pigment epithelium. That leads to loss of photoreceptors, resulting in visual disturbance and difficulty adjusting to low light conditions. Central vision is lost progressively.

The Orbit device was used in the phase I/II trial after initial studies in which palucorel was administered by retinotomy showed there was a risk of retinal detachment. A further study used subretinal delivery, but the technique was judged too technically difficult to take forward.

That led on to the development of Orbit SDS, which was purpose designed for subretinal delivery.

In the 21-patient phase I/II palucorel study the investigators reported that administration to the subretinal site was achieved successfully in most patients and [was] not associated with any moderate or severe, or serious ocular adverse events. The investigators were unable to deliver cells in 3 of 21 participants. Most adverse events were mild and resolved within one month.

Vitrectomy can be associated with an increase in intraocular pressure and accelerated formation of cataracts. No such effects were seen in the Orbit SDS study.

Palucorel is a cell therapy derived from human umbilical tissue that expresses anti-inflammatory factors including interleukin-6, brain-derived growth factor, fibroblast growth factors, and anti-angiogenic thrombospondins. While it showed positive effects in two earlier trials, there were no significant improvements in vision in the Orbit SDS-administered trial.

However, the investigators say, This first in human trial of a suprachoroidal approach for delivery of subretinal liquids was successful from a surgical perspective and clearly demonstrates that subretinal delivery via the suprachoroidal space is feasible.

Gyroscope acquired the Orbit SDA device when it merged with its developer, Orbit Biomedical of Philadelphia in April 2019, to become a fully integrated retinal gene therapy company, with clinical, manufacturing and delivery capabilities.

Orbit Biomedical, now renamed Gyroscope USA Inc., is an ISO 13485 medical device company certified to design, manufacture and distribute ophthalmic surgical instruments.

Following on from the FDA clearance, Arnold said Gyroscope is pursuing a CE mark in Europe for Orbit SDS as well. We also plan to enter into licensing and collaboration arrangements for use of the Orbit SDS by other companies for delivery of gene and cell therapies being developed to treat eye diseases, she said.

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Gyroscope Therapeutics FDA clearance puts subretinal delivery device in Orbit - BioWorld Online

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