Healthpoint Biotherapeutics, of Fort Worth, Texas, began a Phase III trial of its allogeneic living cell bioformulation, HP802-247, for venous leg ulcers. The study will assess wound closure with HP802-247 plus compression therapy over a period of 12 weeks.

"We just dosed our first patient 15 minutes ago," Healthpoint's executive vice President of strategic and commercial development, Rob Bancroft, told BioWorld Today.

The trial will enroll approximately 440 subjects older than 18 who have had venous leg ulcers for at least six weeks, but not more than 24 months. Participants will receive HP802-247 or placebo every 14 days.

About 2.5 million Americans suffer from venous leg ulcers, necessitating a prolonged course of treatment often complicated by setbacks.

HP802-247 is a fibrinogen and thrombin solution that contains living, irradiated, growth-arrested keratinocytes and fibroblasts derived from neonatal foreskins. The product comes in two components: one containing fibrinogen, the other containing thrombin and cells.

"When fibrinogen and thrombin hit each other, they form a gel and sequester the cells on the surface of the wound," Bancroft said.

The cells secrete endogenous growth factors that promote healing.

Previous in vitro studies have shown that HP802-247 releases growth factors and cytokines into the wound, which are thought to interact with the patient's cells to stimulate wound healing.

Healthpoint acquired the product from IsoTis SA in 2003, in a licensing deal that gave IsoTis a long-term share in profits from it. (See BioWorld Today, Aug. 20, 2003.)

IsoTis was acquired by Integra Life Science Holding Corp. in 2007 for $51 million. Bancroft said Healthpoint currently owns all rights to HP802-247.

Neonatal foreskins are a source of tissue that has been exploited for other products, as well. Dermagraft is a product consisting of fibroblasts derived from neonatal foreskins seeded onto a biodegradable scaffold developed by Advanced Biohealing Inc. for diabetic foot ulcers. However, it failed to show superiority over compression therapy for venous leg ulcers, and as a result is not approved for that indication. Shire plc acquired Advanced Biohealing in 2011 for $750 million in cash. (See BioWorld Today, May 19, 2011.)

Apligraf, by Organogenesis Inc., is another biologic product derived from infant foreskins. It is approved for venous ulcers and diabetic foot ulcers.

According to Bancroft, HP802-247 differs from those products in that it stimulates the wounds to heal and regenerate, whereas products like Dermagraft and Apligraf are more like a skin substitute applied to the wound.

Healthpoint's earlier, Phase IIb trial was recently published in The Lancet. It established an optimal dose for the product that was surprisingly the lowest of four dose/frequency combinations tested, one application every two weeks.

Patients in that group achieved 83 percent wound closure. "How much better can you get, in patients that are hard to heal, and have been unresponsive to conservative treatment?" Bancroft asked.

That trial enrolled 228 subjects who received one of four dose regimens of HP802-247 over a 12-week period. In addition to establishing the optimal dose, the trial also showed the product was well tolerated with its most frequent adverse events being skin ulcers, cellulitis, wound infections and skin irritation.

Bancroft added that in an extension trial in which patients were maintained for six months without further doses of the product, the company found that the benefits of therapy were durable for the entire period.

It was unexpected that the lowest dose would have the greatest benefit. Bancroft said Healthpoint is unlikely to carry out a new trial testing even lower doses, because it would be difficult to improve on the 83 percent closure rate already achieved.

He theorized that the low-dose phenomenon could involve a feedback loop of the biological system, but admitted that Healthpoint has not yet figured out the biology behind the dose response.

Trial supplies of HP802-247 will be provided by its research and manufacturing facility in Fort Worth, in which it has recently invested $60 million. New facilities within the complex will include 25,000 square feet of manufacturing infrastructure, labs and clean rooms.

Healthpoint is a profitable company projected to earn $200 million in net revenue in 2012, led by its products Collagenase Santyl Ointment, Oasis Wound Matrix, Oasis Ultra Tri-Layer Matrix and Regranex (becaplermin) Gel 0.01 percent.

In addition to HP802-247, its clinical product pipeline also includes HP828 ointment for partial thickness wounds.