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At ASGT, Acuity Sheds Light on Phase II AMD Study, Aims for Phase III Trial in 07

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BALTIMORE — Acuity Pharmaceuticals announced last week that top-line data from a phase II trial showed that its siRNA-based wet age-related macular degeneration treatment bevasiranib — formerly Cand5 — is both safe and effective.

While the full phase II results will not be released until September at the American Society of Retina Specialists annual meeting in Cannes, France, Acuity co-founder Sam Reich provided some details about the clinical trial's outcome here last week at the American Society of Gene Therapy annual meeting in Baltimore.

Reich, who is also Acuity's vice president of research and development, disclosed time-to-rescue data demonstrating that higher doses of bevasiranib correlated with longer-term efficacy "because it's not one of the specific endpoints that people are used to seeing in wet AMD."

The phase II study enrolled 129 patients with either predominantly classic or active minimally classic AMD, Reich told RNAi News in a follow-up interview this week. "Over the past five or so years, the term 'wet AMD' has been divided into three different types of patients who appear differently on a fluorescein angiography, and also have a different course of progression and severity of disease. The types "range from totally occult to predominantly classic. We took the more aggressive patients in our study," he noted.


"It is a very interesting finding that is indicative of the other results that we will present in September. It just shows that there is a more pronounced clinical effect in those high doses and [treatment] resulted in patients having less likelihood of being put on another therapy — even months after they had gotten their last injection of bevasiranib."

Patients were randomized to receive one of three different dose levels of bevasiranib — either 2 mg, 1.5 mg, or 3 mg per eye — and received two intravitreal injections of the drug, one at the outset of the trial and one at week six.

"They were followed every three weeks to an 18-week visit," Reich said, adding that while the 18th-week visit was the last under the trial's protocol, "on top of that the [US Food and Drug Administration,] for safety reasons, mandates they visit at one year and two years."

According to Reich, the trial's protocol included a provision allowing physicians to "rescue" patients by putting them on another therapy, such as Pfizer's Macugen, "in order to protect their vision and do the best thing for the patient even while conducting clinical research.

"After the 18-week visit, the [requirements] for a doctor to rescue a patient [are] very relaxed … [since] we had collected most of the data we were interested in, and the patients had been off [bevasiranib] for 12 weeks," he said. "The doctors could at that point start treating the patients at their own discretion, essentially.

"What we found with a Kaplan-Meier plot was that there was a much greater likelihood that a patient in a low-dose [cohort] would be rescued and put on another drug than patients [receiving] high doses," he said.

"It is a very interesting finding that is indicative of the other results that we will present in September. It just shows that there is a more pronounced clinical effect in those high doses and [treatment] resulted in patients having less likelihood of being put on another therapy — even months after they had gotten their last injection of bevasiranib," Reich added.

This finding, as well as the yet-to-be released data from the phase II study, "justifies and supports Acuity moving into phase III with this compound" for AMD, Reich said. He added that the company anticipates beginning phase III testing next year.

He added that data from an ongoing phase II study of bevasiranib for diabetic macular edema will likely be presented with the AMD data at ASRS. Phase III development of the drug for DME could also begin sometime next year, he noted.

"We certainly hope to pursue DME, and with the phase II data we'll make a decision about moving into phase III," Reich said.

By next year, Acuity also expects to settle on an indication for a recently acquired anti-inflammatory siRNA drug. In early May, Acuity announced that it had acquired the ophthalmic drug rights to an siRNA targeting Syk kinase from ZaBeCor (see RNAi News, 5/4/2006). ZaBeCor is developing the compound under the name Excellair for asthma (see related story, this issue).

At the time, Acuity President and CEO Dale Pfost declined to comment on which indication the company would likely first pursue with the drug, although Acuity said that preliminary data indicate the siRNA may be useful in ocular inflammatory conditions such as uveitis and ocular allergies.

While Reich said that Acuity is still in the process of reproducing in an ocular setting ZaBeCor's in vivo pharmacologic data in asthma and has not yet settled on any one indication, he hinted that "it could be uveitis."

"I would hope that in 2007 we'd be pursing IND-stage development in [a particular] indication," he added.

Reich also noted that the siRNA could someday be used in conjunction with bevasiranib should both drugs receive regulatory approval.

"There are inflammatory components to wet AMD and DME," he said. "If a physician determines that they need an anti-inflammatory effect, we hope that when this is approved, this is the drug that would be picked up. This drug has the promise of doing everything that steroids do without the side effects."

— Doug Macron ([email protected])