In line with its previously announced expectations, Acuity Pharmaceuticals has filed an investigational new drug application with US regulators to begin phase I testing of its siRNA-based treatment for wet age-related macular degeneration.
The IND filing puts the small Philadelphia-based company on track to begin testing of the drug, called Cand5, as early as September.
Cand5 targets vascular endothelial growth factor, and has been shown in non-human primate experiments to inhibit the neovascular growth and vascular leakage associated with laser injury (see RNAi News, 2/20/2004). These data, along with recently completed ADMET work, have now been submitted to the US Food and Drug Administration, Acuity president and CEO Dale Pfost told RNAi News.
“The preparation work for transitioning into human … testing has been embodied in the IND filing with the protocols, the selection of the [trial] sites, [and the] choosing [of] the people that we’re working with in the clinical trials,” he said.
“We haven’t announced our scientific advisory board as of yet, but there will be key players in [the SAB] that are strategists in clinical trials that have provided us with additional planning towards the [phase I] clinical trial,” Pfost noted. “We’ve added the people who are most relevant to the clinical testing itself, and we will fill it out over the next year.”
One of those slated to join Acuity’s SAB is Alan Gewirtz, a professor at the University of Pennsylvania School of Medicine and inventor of a US patent application (number 20020173478) that forms part of the core of the company’s RNAi intellectual property estate. Acuity has an exclusive license to the patent application from UPenn.
“He will be joining our [SAB] as sort of the RNA-targeted therapies expert,” Pfost said of Gewirtz.
Also expected to join the SAB is Alexander Brucker, a member of Acuity’s board of directors and professor of ophthalmology at University of Pennsylvania Health System’s Scheie Eye Institute, Pfost added.
An announcement regarding the formation of the SAB is expected within the “next couple of months,” Pfost said.
The phase I trial will be a dose-escalating trial evaluating Cand5 in roughly 13 to 19 AMD patients at multiple sites, according to Pfost. “The primary objective in phase I is safety determination,” he said. “That data will come in about three and a half [to] four months from the commencement [of the trial]. We would expect to be able to have data in the first half of ‘05.”
Pfost added that Acuity will evaluate the efficacy of Cand5, as measured by improvements in visual acuity, during the phase I trial. “But it’s not expected that one would find visual acuity correlated to treatment in a relatively short trial with a relatively few number of patients,” he noted.
“That being said, there are surrogate measures that are very important in understanding the disease pathogenesis, and those include the size of lesions … and the leakage … and those are looked upon as very important indicators [of efficacy],” he added.
Supplies of Cand5 for the phase I trial have already been manufactured, and undisclosed sites for the study have been selected based on experience running AMD trials and the ability of the principal investigators to recruit patients, Pfost said.
Pfost declined to comment on the specific design of the phase I study, but said it would begin “well prior to the end of the year. We’d be looking to be able to commence our trial in about a month’s time.”
Assuming the phase I data is positive, Acuity anticipates launching phase Ib and phase II trials simultaneously around the middle of 2005. The phase II trial will be looking for efficacy, while the phase Ib trial will include “an additional safety measure that will be enabling for later trials … to allow us an additional trial design,” Pfost said.
Funding Acuity as it works to move Cand5 through phase II development is a Series B round of financing, worth an expected $15 million, that is in the process of being finalized. “Essentially, we’re down at the detail level — documents and that sort of thing — so [the financing] is in the works,” Pfost said. “We’re working towards the final portions of the close.”
He declined to comment on how the Series B round would impact UPenn’s 25 percent stake in the company.
Go It Alone?
As all the work surrounding Cand5 progresses, Acuity is continuing to weigh the pros and cons of handling the development and commercialization of the drug on its own. About a year ago, Pfost told RNAi News that the company was considering developing and launching Cand5, at least in the US, by itself (see RNAi News, 9/12/2003). In February, he changed his stance somewhat, stating that Acuity expected to develop the drug alone through phase II, at which point other opportunities would be evaluated (see RNAi News, 2/27/2003).
This week, Pfost stepped back somewhat from both statements, leaving the door open for Acuity to take any approach to develop and market its drug.
“In this indication, it’s certainly a very realistic aspiration to take the compound through a substantial fraction, if not all, of the clinical development, and retain [market] rights in major markets, particularly domestic,” he said. “How that will turn out remains to be seen, but it is certainly amongst the options that we are seriously considering and we think is quite reasonable.”
He said that for many indications “you absolutely need to bring a partner in for both clinical development, as well as marketing. In the case of diseases of the back of the eye, and AMD in particular, it is certainly a very distinct possibility that an emerging company can aspire to work through clinical development on their own and be the direct marketer of the compound,” Pfost said.
“Whether or not that will be the outcome in our case has yet to be seen,” he added, declining to comment on whether discussions with possible partners have occurred.