Eye On the Cure Research News

Feb 27, 2020

Researchers Report Six-Month Results from Biogen-Sponsored XLRP Gene Therapy Clinical Trial

Vision improvements observed with medium and high doses

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Clinical researchers at the University of Oxford in the UK have reported initial results for their Phase 1/2 gene therapy clinical trial for people with X-linked retinitis pigmentosa (XLRP) caused by mutations in the gene RPGR. The Biogen-sponsored trial was led by Dr. Robert MacLaren, professor of ophthalmology, University of Oxford. The trial was formerly sponsored by Nightstar Therapeutics (a spinoff of the University of Oxford), which was acquired by Biogen. Initial results from the study were published online in the journal Nature Medicine. The trial is underway at multiple sites in the US and the UK.

Results of the trial were reported for 18 patients in six ascending dosage groups (three patients per group) at six-month follow-up. Overall, six patients, all of whom were in the medium or higher dose groups, demonstrated clinically significant vision gains in retinal sensitivity (as measured by microperimetry) and visual fields. The region of improvement correlated with the site of the subretinal treatment injection.

In their Nature Medicine research paper, Dr. MacLaren and his co-authors said, “In XLRP, the expectation has been stabilization of visual decline by rescuing the remaining cells from cell death, because improvements in visual function above baseline were not previously detected in animal models.” 

Researchers noted that seven of nine patients in the higher dose groups had mild retinal inflammatory responses, which were resolved with oral corticosteroid treatments.

“The results from this early-stage, safety-focused, gene therapy trial for people with XLRP are encouraging, especially given the subjects have advanced retinal degeneration,” says Brian Mansfield, PhD, executive vice president of research and chief scientific officer at the Foundation Fighting Blindness. “We look forward to longer term results as well as results for people with less advanced disease.”

The Biogen XLRP gene therapy involves injection of healthy copies of RPGR underneath the retina. The RPGR copies are contained in a human-engineered virus, known as an adeno-associated virus or AAV, which is designed to readily penetrate retinal cells to deliver the therapeutic genetic cargo.

The Foundation Fighting Blindness funded earlier canine research for an XLRP gene therapy at the University of Pennsylvania School of Veterinary Medicine that informed human studies of the approach.