Gene Therapy Update 1: First Clinical Trial for a Form of Retinitis Pigmentosa (RP) Approved to Begin

In an announcement today, Oxford BioMedica said that it had gained approval from the FDA to begin a Phase I/IIa Clinical Trial for a form of Usher’s Syndrome, Type 1B, which leads to progressive retinitis pigmentosa combined with a congenital hearing defect.

Usher syndrome is the most common form of deaf-blindness which affects approximately 30,000-50,000 patients in the U.S. and Europe. One of the most common subtypes is Usher syndrome type 1B. The disease is caused by a mutation of the gene encoding myosin VIIA (MY07A).

The open label, dose escalation Phase I/IIa study will enrol up to 18 patients with Usher syndrome type 1B at the Oregon Health and Science University's Casey Eye Institute, Portland, Oregon. The study, led by Professor Richard Weleber, will evaluate three dose levels for safety, tolerability and aspects of biological activity and is expected to be initiated by the end of 2011.

Here is the complete news release from Oxford BioMedica:

Oxford BioMedica Announces US IND Approval for Novel Ocular Product in Usher Syndrome Type 1B

Third ocular product partnered with Sanofi approved to enter clinical development

Oxford BioMedica plc announced that the US Food and Drug Administration (FDA) has approved its Investigational New Drug (IND) application for the Phase I/IIa clinical development of UshStat, a novel gene-based treatment for Usher syndrome type 1B. UshStat was designed and developed by Oxford BioMedica using the company’s proprietary LentiVector platform technology and is the third program to enter clinical development under the Phase I/II ocular collaboration agreement signed with Sanofi in April 2009.
                   
The approval of the IND follows the decision by the US Recombinant DNA Advisory Committee (RAC) to approve the UshStat Phase I/IIa protocol in May 2011. The open label, dose escalation Phase I/IIa study will enrol up to 18 patients with Usher syndrome type 1B at the Oregon Health and Science University's Casey Eye Institute, Portland, Oregon. The study, led by Professor Richard Weleber, will evaluate three dose levels for safety, tolerability and aspects of biological activity and is expected to be initiated by the end of 2011.

Usher syndrome is the most common form of deaf-blindness which affects approximately 30,000-50,000 patients in the US and Europe. One of the most common subtypes is Usher syndrome type 1B.  The disease is caused by a mutation of the gene encoding myosin VIIA (MY07A), which leads to progressive retinitis pigmentosa combined with a congenital hearing defect. UshStat uses the company’s LentiVector platform technology to deliver a corrected version of the MYO7A gene to address the vision loss associated with the disease. On the basis of pre-clinical data, it is anticipated that a single application of UshStat to the retina could provide long-term or potentially permanent stabilization of vision. There are currently no approved treatments available for Usher syndrome type 1B. UshStat has received European and US Orphan Drug Designation which brings development, regulatory and commercial benefits.

John Dawson, Chief Executive Officer of Oxford BioMedica, said: "This is the third ocular IND approval that Oxford BioMedica has received from the US regulatory agencies over the last 12 months which represents an exceptional achievement for our R&D and regulatory teams. The continued progress of our ocular program partnered with Sanofi will further support the development path for other LentiVector platform products. With no approved treatment available for patients, we look forward to bringing UshStat into Phase I/IIa clinical development later this year."

Professor Richard Weleber, Principal Investigator at the Casey Eye Institute, commented: "We are delighted to be partnering with Oxford BioMedica in the design and conduct of this; the first trial of gene replacement for retinitis pigmentosa associated with myosin 7A-deficient type I Usher syndrome. As such, this trial represents a major milestone in the history of Usher syndrome. We conclude that the gene replacement therapy that will be evaluated in this trial has the potential to provide a substantial, durable benefit for the vision of these patients."

Dr Stephen Rose, Chief Research Officer of the Foundation Fighting Blindness, an early funding collaborator of Oxford BioMedica's pre-clinical ocular program, added: "The IND approval for UshStat is great news for people affected by a particularly devastating condition. UshStat will be the first vision treatment for any type of Usher syndrome to move into a human study and, as a corrective gene therapy, it holds potential to halt the disease in its tracks."


Editor’s Note: The other two programs involving gene therapy for ophthalmic applications that Oxford BioMedica is involved with, with Sanofi, are RetinoStat for treating the wet form of age-related macular degeneration, a Phase I study; and the treatment of Stargardt’s disease, using StarGen, a Phase I/II study.

If you have Usher Syndrome, Type 1B, or know someone who does, and would like more information about the study, please contact Maureen Toomey, Study Coordinator for the UshStat trial, at the Casey Eye Institute at toomeym@ohsu.edu.

Also, for additional background information on the use of gene therapy in the treatment of RP and dry AMD, please see my article: “The Use of Gene Therapy in Treating Retinitis Pigmentosa and Dry AMD”.