Medical Device Daily

Data reported from two separate studies have shown that gene therapy improved the vision of some patients with a rare inherited degenerative eye disease that leads to blindness by age 30.

Targeted Genetics (Seattle) reported that its gene therapy improved the vision of at least one patient with Leber congenital amaurosis (LCA), a group of inherited blinding diseases that damages light receptors in the retina.

That news triggered a 22.37% jump in the firm's stock (Nasdaq:TGEN).

However, that increase was not sufficient to push Targeted Genetics' stock price over $1 a share to meet the Nasdaq market's minimum listing requirement. The company said earlier this week that it had until Oct. 20 to regain compliance.

Shares of Targeted Genetics closed at 93 cents Monday, an increase of 17 cents.

A second study using a gene therapy produced by the Children's Hospital of Philadelphia (CHOP) showed evidence of improvement in retinal function in three patients with LCA.

Both studies used a recombinant adeno-associated viral (AAV) vector delivery of the human retinal pigment epithelium-specific 65 kDa protein gene (RPE65), administered as a subretinal injection during an ophthalmology surgical procedure known as vitrectomy.

While both trials showed the therapy to be safe in the short term, one patient in the CHOP trial experienced an adverse event known as a macular hole, which the investigators said was more than likely caused by contraction of a pre-existing epiretinal membrane after surgery.

There have been no reported adverse events for patients participating in the Targeted Genetics study, lead investigator Robin Ali, professor of human molecular genetics at the University College of London, told Medical Device Daily's sister publication, BioWorld Today.

Researchers for the Targeted Genetics Phase I/II study, which was conducted in conjunction with the University College London's Institute of Ophthalmology and the Moorfields Eye Hospital (London), reported data about three young adults two men ages 18 and 23, and one girl age 17 with a progressive deterioration in vision caused by an abnormality in the RPE65 gene who were administered the firm's tgAAG76 during vitrectomy surgery.

The first patient underwent the procedure on Feb. 7, 2007, said James Bainbridge, the retinal surgeon who implanted the gene therapy, which consists of hundreds of billions of AAV vector particles that carry the RPE65 gene.

A second patient was administered tgAAG76 on April 25, 2007, and a third person, 18-year-old Steven Howarth, received Targeted Genetics' gene therapy July 11.

The procedure took about 90 minutes for each patient, Bainbridge said.

"The gene vector has to be delivered underneath the retina in the back of the eye, so it is quite a complicated surgical procedure," he said.

Bainbridge noted that each patient has so far received the therapy in one eye only.

Ali said it is too early to know how soon the gene therapy could be safely administered in the study participants' untreated eyes.

The three young adult patients in the Phase I/II study were selected for the trial because they retained a limited degree of residual retinal function despite advanced retinal degeneration, and they might therefore be expected to benefit from intervention, he explained.

The researchers detected no dissemination of the vector, and there were no immune responses identified in any of the patients, Bainbridge said.

"We showed that it was safe, but were very pleased to see what we hadn't expectec that in one of those subjects we saw a therapeutic effect," he said.

Rigorous testing in three areas, Ali said, confirmed that there was significant improvement in the night and peripheral visions for Howarth, the young adult who received the gene therapy in July.

A "very compelling" aspect of the positive outcome for Howarth, Ali said, is the patient's "own perception of his improved vision."

"He reports a change in his behavior, and it's made a real difference in his life so that he is therefore much more confident about staying out late at night and coming home by himself without help."

The study's results ultimately showed that small changes in retinal function "can have a major change in terms of clinical benefit," Ali said.

Barrie Carter, chief scientific officer for Targeted Genetics, noted that the Phase I/II study has enrolled 12 patients—the three young adults for which data were reported, and nine children ages 8-16.

Only one child, an 11-year-old boy, so far has received Targeted Genetics' gene therapy, Ali said. No data is available yet for that patient, he added.

Because LCA is less advanced in younger children, Ali said, the researchers anticipate that tgAAG76 will have a greater effect in the younger age group.

Results from the CHOP study showed that three patients between the ages of 19 and 26 had modest improvements in measures of retinal function on subjective tests of visual acuity.

Although the follow-up was very short, and normal vision was not achieved, the CHOP investigators said their study "provides the basis for further gene therapy studies in patients with LCA."