By Karen Pihl-Carey

Staff Writer

United Therapeutics Corp. completed patient enrollment in its second Phase III study of its lead compound, UT-15, to treat pulmonary hypertension (PH).

If all goes well, analysts expect the company will file a new drug application by the third quarter of 2000.

The second Phase III trial is being conducted at 15 medical centers in Europe, Israel and Australia and 19 centers in North America. Both trials enrolled more than 450 advanced PH patients at 40 medical centers total.

The trials are randomized, placebo-controlled and double-blind studies that will determine the impact of continuous subcutaneous UT-15 therapy on exercise capacity at 12 weeks. London-based Glaxo Wellcome plc's Flolan, the only therapy approved for the indication of advanced PH, used the same efficacy measurement in its regulatory filing.

The enrollment completion comes about a month to six weeks ahead of plan and may indicate a high level of interest by physicians and patients, said analyst Kevin Tang of New York-based Deutsche Banc Alex. Brown.

"We're very excited about it. There's a tremendous unmet need for pulmonary hypertension patients," Tang told BioWorld Today. "We think the completion of it ahead of schedule really testifies to the physician and patient demand for a better therapy."

Tang's firm acted as lead manager of United Therapeutics' initial public offering of 4.5 million shares at $12 each in June. The IPO raised $54 million, not including a 15 percent overallotment option, which was exercised in full. The option raised an additional $8.1 million. United's stock (NASDAQ:UTHR) closed Tuesday at $40.75, up $1.50.

Results from the two trials will form the basis for a regulatory filing in the U.S., Europe and other markets, the company said. Tang expects NDA submissions in the early third quarter of 2000 and a product launch in early 2001.

UT-15 has a sales potential of more than $250 million, assuming a 10 percent or more market penetration, Tang said.

"We think $250 million is probably conservative," he added. "I think realistically it could be double that though."

Flolan is estimated to have achieved sales of about $100 million in 1998.

Advanced pulmonary hypertension is a life-threatening condition characterized by high pressure in the blood vessels between the heart and lungs and appears to be associated with the reduced production of prostacyclin in the affected blood vessels. Symptoms include shortness of breath and fainting, and if left untreated, the condition can result in death within three years.

Flolan (prostacyclin), approved in 1995, is the current therapy for advanced PH. The drug is effective, but it is unstable and has a short circulating half-life of less than six minutes, Tang said. The drug exposes patients to a high risk of infections because it is delivered intravenously through a catheter surgically implanted into a patient's chest.

UT-15 is a chemical analogue of prostacyclin that is stable at room temperature for up to five years and has a circulation half-life of 45 minutes. It is delivered through a subcutaneous port by a microinfusion device. The drug is prepackaged as a sterile liquid and is changed by the patient about once every three days, whereas Flolan needs to be reconstituted several times a day under completely sterile conditions, Tang said.

UT-15 is expected to be as effective as Flolan, he said. "The difference is Flolan needs to be delivered through a surgically implanted catheter into the heart for 24 hours a day. That opens up the risk of infection," he said. "UT-15 is delivered with the same kind of device that delivers insulin to diabetics. It's a little MiniMed pump, infused through a tiny little needle under the belly. You can go swimming with it on. You can take showers. And it's just very non-invasive. There's virtually zero risk of infections."

United Therapeutics, which is based in Silver Spring, Md., and Research Triangle Park, N.C., is a company with a focus in chronic vascular diseases. It was founded in 1996 by an entrepreneur and a drug development team from the Burroughs Wellcome Fund, of Durham, N.C.

Its pipeline includes beraprost, which is moving into a second Phase III trial. The orally delivered beraprost is an alternative for treatment of peripheral vascular disease. Analysts expect it will receive European approval in the first quarter of 2000. Deutsche Banc Alex. Brown estimated UT-15 and beraprost will generate annual sales of more than $500 million for United Therapeutics.