Gene Therapy in Ophthalmology Update 9: Oxford BioMedica/OHSU Preparing to Treat First Usher Syndrome Patient & Oxford BioMedica Ophthalmic Program Update

In an announcement today from the Foundation Fighting Blindness, and confirmed by Oxford BioMedica, the Casey Eye Institute of the Oregan Health & Science University (OHSU) is preparing to treat the first Usher Syndrome patient under the clinical protocol designed by Oxford BioMedica using its UshStat gene therapy treatment.

(For more information about this study, please see my Update 1: First Clinical Trial for a Form of Retinitis Pigmentosa (RP) Approved to Begin)

Here is the complete text of the FFB news release:

Usher Syndrome Gene Therapy Study Begins in Oregon

March 6, 2012 - The first-ever gene therapy for Usher syndrome, a devastating condition that causes both blindness and deafness, has moved into a Phase I/IIa clinical trial at the Foundation-funded Casey Eye Institute, Oregon Health & Science University (OHSU). The research team, led by Dr. Richard Weleber, is preparing to treat its first patient.

Developed by Oxford BioMedica, a biopharmaceutical company in the U.K. and a Foundation partner, the UshStat treatment is designed to halt vision loss in people affected with Usher syndrome type 1B, which is caused by defects in the MY07A gene. Based on results in lab studies, researchers believe a single UshStat treatment may last several years, perhaps a lifetime.

"We are delighted to see Oxford's innovative gene therapy for Usher 1B move into human studies. It is a critical milestone in our campaign to overcome vision loss from a particularly challenging condition," says Dr. Stephen Rose, the Foundation's chief research officer. "UshStat is great news for the Usher syndrome community, because there are virtually no vision-related treatment options available for any form of the disease. While the treatment is for Usher 1B, success in the trial will open the door for using gene therapy to treat other forms of Usher syndrome."

UshStat is the third Oxford BioMedica gene therapy to move into a clinical trial. StarGen, the company's gene therapy for Stargardt disease, is in a Phase I/IIa human study at OHSU and the Centre Hospitalier Nationale d'Ophthalmologie des Quinze-Vingts in Paris. The company's RetinoStat, a gene therapy for wet age-related macular degeneration, is in a Phase I clinical study at Wilmer Eye Institute at Johns Hopkins Hospital in Baltimore, Maryland.

Oxford says that the first six patients in the RetinoStat trial and the first four in the StarGen study are doing well. No safety issues or adverse events have occurred. The company will report additional results for RetinoStat in the first half of 2012 and for StarGen in the second half of the year.

The two-year UshStat study will enroll 18 patients affected by Usher syndrome type 1B. One eye of each patient will be injected with the therapy. The trial will evaluate the treatment's safety as well as changes in retinal function of the treated eye versus the untreated eye.

To participate in the UshStat trial, patients will need to be 18 years or older and have had a genetic test confirming the diagnosis of Usher syndrome type 1B. For more information on trial participation, visit the clinical trials page of the Foundation's website, which requires registration.

The UshStat treatment is contained in a tiny drop of liquid that is injected beneath the retina and absorbed by retinal cells in a matter of hours. The treatment uses Oxford's LentiVector gene delivery technology, a re-engineered virus, to enable healthy copies of the MYO7A gene to penetrate the cells. A key benefit of the LentiVector technology is its ability to deliver large genes, like MYO7A, which other viral systems are not able to deliver.

Usher syndrome is the leading cause of combined deafness and blindness in the world. It affects approximately 45,000 people in the United States. There are three primary types of Usher syndrome, designated by numerals, and 12 subtypes, designated by letters.

"We are excited about the potential for our powerful gene therapy technology to save and restore vision, and we are grateful to the Foundation Fighting Blindness for playing a critical role in moving it out of the lab and into clinical trials. It has been an outstanding partnership," says Stuart Naylor, Ph.D., chief scientific officer, Oxford BioMedica.

In addition, Oxford BioMedica provided some updated information about its other ophthalmic gene therapy programs, as part of the release of its end of year report.

Lead RetinoStat Phase I trial in “wet” AMD on track

Six patients have been treated with RetinoStat in the on-going US Phase I study in neovascular “wet” age-related macular degeneration (AMD). Three patients received the first dose level, three received the second dose level and the third patient cohort (dose level 3) is underway. The open label, dose escalation Phase I study will enroll 18 patients with “wet” AMD at the Wilmer Eye Institute at Johns Hopkins, Baltimore (USA). Led by Professor Peter Campochiaro, the study will evaluate three dose levels and assess safety and aspects of ocular physiology. Oxford BioMedica is on track to announce first results in H1 2012.

First gene therapy clinical trials in Stargardt disease and Usher syndrome underway

There are currently no approved treatments for Stargardt disease and Usher syndrome type 1B and other potential strategies do not target the root cause of the disease. As such, StarGen and UshStat have received both European and US Orphan Drug Designation which brings development, regulatory and commercial benefits.

In June 2011, the first patient in the StarGen Phase I/IIa study in Stargardt disease was treated in the US.

In July 2011, the French regulatory agency (AFSSAPS) approved the opening of a second clinical site in France. In the US, the study is led by Professor David Wilson at the Oregon Health & Science University, Portland, Oregon. In France, Professor Jose-Alain Sahel leads the study at the Centre Hospitalier National D'Opthalmologie des Quinze-Vingts, Paris.

Four patients have been treated to date at the first dose level and the second cohort using dose level 1 in earlier-stage patients is underway. The open label, dose escalation Phase I/IIa study will enroll up to 28 patients and will evaluate three dose levels for safety, tolerability and aspects of biological activity. First results are expected in H2 2012.

In February 2012, the UshStat Phase I/IIa study in Usher syndrome type 1B commenced in the US at the Oregon Health & Science University's Casey Eye Institute. Led by Professor Richard Weleber as Principal Investigator, the open label, dose escalation Phase I/IIa study will enrol up to 18 patients and will evaluate three dose levels for safety, tolerability and aspects of biological activity. Initial results are expected in H2 2012.

Glaucoma-GT: new collaboration with Mayo Clinic for chronic glaucoma

In October 2011, Oxford BioMedica entered into a research and development collaboration with Mayo Clinic, Rochester (USA) to develop a novel gene therapy for the treatment of chronic glaucoma. Under the terms of the agreement, Mayo Clinic and Oxford BioMedica will undertake pre-clinical studies to establish the feasibility of treating glaucoma using Oxford BioMedica's proprietary LentiVector gene delivery technology expressing a COX-2 gene and a PGF-2α receptor gene to reduce intraocular pressure.

Since the start of the collaboration, the teams have successfully initiated the first pre-clinical study which aims to demonstrate gene transfer using Oxford BioMedica’s LentiVector platform technology to target ocular tissues following transcorneal administration. Preliminary results from this study are encouraging and indicate effective and robust gene transfer into the target ocular tissues. A second pre-clinical study is expected to begin in Q2 2012 to evaluate the lowering of intraocular pressure following administration of the collaboration’s Glaucoma-GT.