David Hutton

home

authors

david-hutton

This week, Editas Medicine Inc. announced the administration of EDIT-101, an experimental CRISPR gene editing medicine, to the first paediatric patient enrolled in the Brilliance clinical trial, which is designed to test the safety of EDIT-101 for the treatment of Leber congenital amaurosis 10 (LCA10), a 

-related group of inherited retinal degenerative disorders caused by mutations in at least 18 different genes. It is the most common cause of inherited childhood blindness, with an incidence of two to three per 100,000 live births worldwide.

According to the company, this marks the world’s first in vivo dosing of a paediatric patient with a CRISPR gene editing experimental medicine.

“Administering the experimental medicine to the first paediatric patient in the BRILLIANCE trial marks a significant milestone toward delivering on the potential of CRISPR gene editing medicines being safe and effective in treating LCA10, which often results in significant vision loss and blindness early in life,” James C. Mullen, chairman, president, and CEO, Editas Medicine, said in a statement. “Currently, there are no approved treatments for LCA10, and we look forward to sharing future updates from the BRILLIANCE trial, including sharing additional clinical data, later this year.”

EDIT-101 is a CRISPR/Cas9-based experimental medicine under investigation for the treatment of Leber congenital amaurosis 10 (LCA10), a CEP290-related retinal degenerative disorder. EDIT-101 is administered via a subretinal injection to reach and deliver the gene editing machinery directly to photoreceptor cells. EDIT-101 has been granted Rare Paediatric Disease and Orphan Drug designations from the U.S. Food and Drug Administration (FDA) and Orphan Designation from the European Medicines Agency (EMA).

The company noted that its BRILLIANCE Phase 1/2 clinical trial (NCT03872479) of EDIT-101 for the treatment of Leber congenital amaurosis 10 (LCA10) is designed to assess the safety, tolerability, and efficacy of EDIT-101 in patients with this disorder. Clinical trial sites are enrolling up to five cohorts testing up to three dose levels in this open label, multi-centre study. Both adult and paediatric patients (3 to 17 years old) with a range of baseline visual acuity assessments are eligible for enrolment. Patients receive a single administration of EDIT-101 via subretinal injection in one eye. Patients are monitored every three months for a year after dosing and less frequently for an additional two years thereafter.

“Enrolling this first paediatric patient in the Brilliance trial is an important step toward bringing potentially life-changing treatments to children with genetic retinal diseases,” Tomas S. Aleman, MD, the Irene Heinz-Given and John LaPorte Research Associate Professor at the Scheie Eye Institute of the Perelman School of Medicine at the University of Pennsylvania, and a retinal degeneration specialist with the Division of Paediatric Ophthalmology at Children's Hospital of Philadelphia (CHOP), said in a statement. “We are excited to be involved in research focused on testing potential new treatments for untreatable diseases like LCA10.”

Aleman also is the trial principal investigator for the site.

Albert M. Maguire, MD, the F.M. Kirby Professor of Molecular Ophthalmology at Penn and a member of the Centre for Advanced Retinal and Ocular Therapeutics, is the surgeon in the trial, in collaboration with Children’s Hospital of Philadelphia (CHOP), the nation's first hospital devoted exclusively to the care of children and the source of many breakthroughs and firsts in paediatric medicine. CHOP’s Clinical In Vivo Gene Therapy (CIGT) program provided the clinical operations support to conduct the work at CHOP.

According to the company, it initiated enrolment in the paediatric mid-dose cohort in the BRILLIANCE trial following the Independent Data Monitoring Committee (IDMC) endorsement based on an analysis of safety data from a clinical trial in adult patients that tested low-dose and mid-dose levels of the experimental medicine. The Company remains on track to complete testing of the paediatric mid-dose in the first half of 2022 and expects to initiate testing of the paediatric high-dose this year.

Previously, Editas Medicine completed dosing of all adult cohorts in its BRILLIANCE study and announced preliminary EDIT-101 clinical results demonstrated a favourable safety profile and encouraging signals of clinical benefit. The Company expects to provide a clinical update on the BRILLIANCE trial in the second half of 2022.

The update is expected to provide safety and efficacy assessments on all adult patients who have had at least six months of follow-up evaluations, which will include at least 12 months of data on the adult mid-dose cohort, and at least six months of data on the adult high-dose cohort. Additionally, the Company is expanding enrolment in one or more of the previously completed adult cohorts to explore dose response and support establishment of registrational trial endpoints, which are anticipated by year-end.

Articles

The trial marks the first-ever in vivo delivery of an experimental CRISPR gene editing medicine to a paediatric patient, with the company on track to complete dosing of the paediatric mid-dose cohort in the first half of 2022.

First paediatric patient dosed in BRILLIANCE Phase 1/2 clinical trial for LCA10

Skye Bioscience Inc. this week announced the release of preclinical data

 demonstrating stronger and longer-lasting reduction of intraocular pressure (IOP) when Skye’s proprietary molecule, SBI-100, is formulated as a nanoemulsion containing the mucoadhesive agent Carbopol 940.

In a news release, Skye, in collaboration with investigators at the University of Mississippi, previously published preclinical data

 demonstrating SBI-100 formulated as a nanoemulsion (THC-VHS-NE) achieved greater reduction of intraocular pressure in non-pigmented rabbits than both latanoprost and timilol, the current first and second line treatments for glaucoma, respectively. The current study was undertaken to determine if the inclusion of a mucoadhesive agent could prolong the intensity and duration of action of the THC-VHS-NE formulation through increased residence time or penetration, or both, to potentially achieve once- or twice- a day dosing.

According to the release, in this study sponsored by Skye, researchers at the University of Mississippi compared the reduction of IOP in normotensive rabbits with a single treatment of THC-VHS-NEC (SBI-100 formulated as a nanoemulsion with Carbopol 940) compared to latanoprost, the commercial standard of care; THC-NEC (native THC formulated as a nanoemulsion with Carbopol 940); and THC-VHS-NE (SBI-100 formulated as just a nanoemulsion). When comparing each treatment group, THC-VHS-NEC, Skye’s SBI-100 ophthalmic emulsion, demonstrated the greatest intensity and duration of IOP-lowering.

Punit Dhillon, CEO and chairman of Skye, noted in the news release that the company has been working aggressively to optimize a formulation of SBI-100 to advance toward a first in-human study, which is planned to start this quarter.

“We previously reported strong preclinical results that highlighted the superior IOP-lowering of our unique molecule formulated as just a nanoemulsion compared to other established commercial glaucoma drugs,” Dhillon said in the release. “This further evolution of our formulation, generating even more robust results, gives us strong conviction as we step into the clinic with SBI-100 ophthalmic emulsion.”

Dhillon added that the company’s goal with this program is to advance a new class of glaucoma treatment with a once or twice a day dosing regimen.

“Positive, prior third-party research relevant to our molecule and this preclinical work informed our selection of the best formulation of SBI-100 for this application,” Dhillon concluded.

In comparison to THC-VHS-NE, THC-NEC and commercial latanoprost, THC-VHS-NEC (SBI-100 ophthalmic emulsion) exhibited a prolonged duration of action. THC-NEC and THC-VHS-NE formulations respectively produced an average maximum drop in IOP of 3.7 mm Hg at 60 minutes and 4.8 mm Hg at 150 minutes, while the IOP-lowering effect lasted for 240 and 360 minutes, respectively, in the treated eye. In contrast, SBI-100 ophthalmic emulsion lowered IOP by 4.5 mmHg at 60 min and maintained this drop for at least 480 min in the treated eye.

 < 0.05) in IOP-lowering was also observed between SBI-100 Ophthalmic Emulsion and commercial latanoprost ophthalmic solution. The average maximum drop in IOP with SBI-100 ophthalmic emulsion (THC-VHS-NEC) of 4.5 mm Hg at 60 minutes was almost twice that obtained with commercial latanoprost ophthalmic solution (2.3 mm Hg) at 60 minutes.

Moreover, latanoprost maintained IOP 10% below baseline for only 360 minutes, whereas SBI-100 ophthalmic emulsion maintained the IOP- lowering effect for at least 480 min (

1. Sweeney, C., Dudhipala, N., Thakkar, R., et al. Impact of mucoadhesive agent inclusion on the intraocular pressure lowering profile of Δ9-tetrahydrocannabinol-valine-hemisuccinate loaded nanoemulsions in New Zealand white rabbits. Int’l Journal of Pharmaceitics. Published March 25, 2022. https://doi.org/10.1016/j-ijpharm.2022.121564

2. Sweeney, C., Dudhipala, N., Thakkar, R. et al. Effect of surfactant concentration and sterilization process on intraocular pressure–lowering activity of Δ9-tetrahydrocannabinol-valine-hemisuccinate (NB1111) nanoemulsions. Drug Deliv. and Transl. Res. 11, 2096–2107 (2021). https://doi.org/10.1007/s13346-020-00871-9

In research sponsored by Skye Bioscience Inc., investigators at the University of Mississippi have demonstrated stronger and longer-lasting reduction of intraocular pressure when a proprietary molecule, SBI-100, is formulated as a nanoemulsion containing the mucoadhesive agent Carbopol 940.

Nanoemulsion formulation enhances IOP reduction, study finds

, sits down with Michael Watson, Vice President of OraNet to discuss this year’s most pressing challenges in clinical research: From the overburdening of sites with studies delayed by COVID to difficulties with staff retention and how holistic site support and patient solutions can provide enough to relief to keep projects on time and within budget.

Videos

Mike Watson, Vice President of OraNet, unpacks some of the most pressing challenges to clinical research in today’s climate.

Tackling today’s top challenges of clinical research

, sits down with David Bingaman, DVM, PhD, Chief Development Officer of Ora Clinical to discuss the need to accelerate clinical trials and increase investments in retina research. Dr. Bingaman also discusses Ora Clinical’s presence at ARVO 2022.

Dr David Bingaman of Ora Clinical discusses today’s need to accelerate clinical studies and increase investments in retina and challenging disease states.

Author | David Hutton

Articles

Nanoemulsion formulation enhances IOP reduction, study finds

Tackling today’s top challenges of clinical research

Unpacking the need to accelerate clinical studies in retina

First paediatric patient dosed in BRILLIANCE Phase 1/2 clinical trial for LCA10