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Acuity Begins Second Phase II Trial, This Time in Macular Edema; AMD Trial Completes Patient Dosing


Acuity Pharmaceuticals announced last week that it has begun testing its siRNA drug Cand5 in a pilot phase II trial for diabetic macular edema, and that it has also completed patient dosing of the drug in its phase II trial for age-related macular degeneration.

The company said that the DME study is expected to wrap up by the end of 2006, while data from the AMD trial are expected by mid-year. A phase III trial of Cand5 in AMD is expected to begin sometime in 2007.

Although it bills itself as an ophthalmic company, Acuity has been at the forefront of the RNAi sector ever since November 2004 when it began phase I testing of Cand5, an siRNA targeting vascular endothelial growth factor, in AMD — the first time an RNAi-based therapeutic was tested in humans (see RNAi News, 11/12/2004).

Other companies have since followed suit: Sirna Therapeutics began phase I testing of its own AMD drug, Sirna-027, a few weeks after Acuity moved Cand5 into the clinic (see RNAi News, 11/26/2004); and in December, Alnylam Pharmaceuticals began phase I testing of an siRNA treatment for respiratory syncytial virus after dropping plans to develop its own AMD therapy (see RNAi News, 12/9/2005).

But Acuity has maintained its lead, advancing Cand5 into phase II testing in October 2005 (see RNAi News, 10/21/2005). That study — nicknamed CARE for Cand5 Anti-VEGF RNAi Evaluation — is a randomized, double-masked trial evaluating the drug in 129 patients at 28 sites. Patients in the CARE study received one of three doses of Cand5, the highest being 3 mg, once every six weeks via intravitreal injection.

"We are looking at the technologies of RNA interference as being very appropriate for us … but we are not limiting ourselves to RNAi at all. We see ourselves as being, first and foremost, as an ophthalmology company."

This trial is designed to measure the effect of Cand5 on visual acuity, examining, among other things, the size and thickness of ocular lesions using fluorescein angiography and optical coherence tomography.

In line with previously disclosed estimates, Acuity has also begun dosing patients in a phase II study evaluating Cand5 in DME, a condition related to AMD characterized by swelling of the retina in diabetics due to fluid leaking from blood vessels in the macula.

This trial — called RACE for RNAi Assessment of Cand5 in diabetic macular Edema — is examining the safety and preliminary efficacy of three dose levels of Cand5, administered by intravitreal injection, in 48 patients. The study is evaluating safety, as well as "all the appropriate measures, including best corrected visual acuity and OCT measurements," Acuity President and CEO Dale Pfost told RNAi News this week.

Filling Out Its Pipeline, Hedging Its Bets

Although a phase III trial of Cand5 in AMD is expected to begin sometime next year, there is no guarantee that the drug will make it to the market. As such, Acuity has begun taking steps to fill out its pipeline — all the while sticking to its core competency in ophthalmology.

According to Pfost, the company is now looking at a number of targets for ophthalmic drug development. He declined to comment in any detail on them, but noted that "we now are very eager to be broadening that pipeline in ways that we'll be able [to talk about] … in later '06 and '07."

He added that Acuity is also investigating the possibility of using Cand5 in indications beyond AMD and DME. "There are several indications [where Cand5 may be effective], and … we'll be prioritizing which of the indications to move into," Pfost said.

As part of Acuity's overall R&D effort, the company has also initiated a program to develop a topical delivery technology that could be used with Cand5 and other drugs, including new RNAi-based ones, Pfost said.

"We are looking at the technologies of RNA interference as being very appropriate for us … but we are not limiting ourselves to RNAi at all," he said. "We see ourselves as being, first and foremost, an ophthalmology company."

That said, Pfost stressed that "RNA interference is an exceedingly important area for us," and added that of the two or more investigational new drug applications the company anticipates filing in 2007 and 2008, at least one "would be [for] an additional siRNA-based drug."

Business Side of Things

As research and development moves forward at Acuity, the company is also evaluating its various business options.

For small biotechnology firms, including those in the RNAi space, partnering drug candidates with bigger players is often the key to success. Alnylam has signed a number of broad deals to develop drugs in various indications with big pharmas and big biotechs, including Merck and Novartis (see RNAi News, 7/2/2004 and 9/9/2005), while Sirna recently out-licensed its own AMD candidate, Sirna-027, to Allergan (see RNAi News, 10/7/2005).

Pfost declined to comment on whether Acuity is actively negotiating with potential partners for Cand5 or other drugs, but said that the company is "exploring the options and opportunities to partner with companies."

He stressed that this option is not necessary for survival, however. "It is in the case of ophthalmology in general, and specifically the diseases of the back of the eye, that it is a reasonable aspiration for an emerging biotechnology company to consider going directly to … the domestic market" on its own, he said. "That opportunity is still there for us."

— Doug Macron ([email protected])

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