Vical Inc. said licensee AnGes MG Inc. reached an agreement with the FDA on the design of a 560-patient Phase III trial of Collategene, a potential treatment for patients with peripheral arterial disease (PAD).

But AnGes is unlikely to start the Phase III Collategene trial until it receives approval of the drug in Japan, where the product currently is under review, according to Vical. Osaka, Japan-based AnGes also is seeking a U.S. partner to run the trial, which was worked out with the FDA under a special protocol assessment (SPA).

The trial was designed in a way that would allow it to file for approval of Collategene in several countries, including Canada, Europe, Latin America, other markets beyond Japan as well as the U.S., Vical said.

The only two late-stage drugs in development for lower limb ischemia are both licensees of Vical, Alan R. Engbring, head of investor relations at Vical, told BioWorld Today. He said other such products are earlier stage.

San Diego-based Vical developed the underlying gene-delivery technology behind Collategene and another late-stage angiogenesis treatment being developed by Paris-based Sanofi-Aventis Group. Sanofi has completed enrollment in a 500-patient pivotal Phase III trial of its FGF-1 angiogenesis treatment for advanced PAD and expects final data from that trial in late 2010.

Currently, no drugs are approved specifically for PAD, a disease characterized by the buildup of plaque in arteries (atherosclerosis). It is caused mostly by atherosclerotic narrowing of lower limb arteries that significantly reduces the blood flow to those limbs.

Surgical procedures typically are used to address issues related to lack of blood flow in patients with lower limb ischemia. Angioplasty or stent placement often are used to treat PAD, but those procedures frequently result in restenosis, or re-narrowing of the artery.

AnGes' Phase III trial will enroll patients of last resort who have run out of options and will likely need amputations. The trial also will enroll patients with "poor options" who are unable to receive endovascular (product,search) surgery due to their vascular anatomy or severe co-morbid disease.

By including poor-option patients, the trial will be open to at least three to four times as many target patients compared to other trials within the industry, which only include no option patients, Vical said.

Patients who are typically prone to lower limb ischemia are primarily those with diabetes, but it also can develop in individuals with atherosclerosis or cardiovascular issues.

Cambridge, Mass.-based Pervasis Therapeutics Inc. has a Phase I tissue-engineered allogeneic endothelium product (PVS-10200) aimed at PAD. The drug candidate, supported by a $17 million venture funding round announced last year, is designed to deliver allogeneic endothelial cells, encapsulated in a polymer matrix, to the site of stent placement to re-establish the vasculature and prevent the inflammatory and thrombotic effects that lead to restenosis. (See BioWorld Today, Sept. 17, 2009.)

Pluristem Therapeutics Inc., of Haifa, Israel, this week reported interim results from Phase I trials of placenta-derived cell therapy candidate PLX-PAD in critical limb ischemia, suggesting that the drug is safe and potentially efficacious. Results also showed that patients had experienced no significant unfavorable effects related to PLX-PAD administration.

Sunrise, Fla.-based BioHeart Inc. has developed a device, the TGI System, that mixes stem cells derived from a patient's own fat tissue to create a minimally manipulated stem cell therapy to help heal damaged blood vessels in the lower limb. In the U.S., BioHeart is seeking clearance to test the device in vascular grafts in lower limb ischemia. In addition, BioHeart is considering an indication for the device.

Shares in Vical (NASDAQ:VICL) were down 3 cents, closing at $3.44.