Providing a new, less-invasive treatment option for pulmonary arterial hypertension patients, CoTherix Inc. received FDA approval for Ventavis, an inhaled product in-licensed from Schering AG in October 2003.

The news came in after the market closed Wednesday. South San Francisco-based CoTherix's stock (NASDAQ:CTRX) rose 20.4 percent, or $2.04 on Thursday, to close at $12.02.

CoTherix intends to launch the product in the second quarter for the treatment of pulmonary arterial hypertension (PAH) in patients with New York Heart Association (NYHA) Class III or IV symptoms.

"This is the most extraordinary event in our five-year history," Donald Santel, CoTherix's CEO, told BioWorld Today.

It is the company's first approval for a drug that represents its entire pipeline, and one that has been owned for a little over a year. The company is actively looking for other drugs to in-license, Santel said.

CoTherix filed the new drug application in June, only nine months after it in-licensed the product from Schering, which markets it in several European countries and Australia. The NDA was granted priority review and orphan drug designation by the FDA in August.

Gur Roshwalb, a research analyst with Piper Jaffray & Co. in New York, said Ventavis sales are expected to be about $7.5 million in 2005, $40 million in 2006, and reach a peak of $250 million in 2010.

The orphan drug designation gives CoTherix several years of marketing protection.

"The composition-of-matter patent expired in September of this year," Santel said. "We have seven years of market exclusivity from [Wednesday] afternoon."

In clinical trials, Ventavis (iloprost) inhalation solution has been shown to be well tolerated. The most common side effects were reddening of the face, increased cough, low blood pressure, headaches, nausea, spasm of the jaw muscles and fainting. Serious adverse events included congestive heart failure, chest pain, supraventricular tachycardia, dyspnea, peripheral edema and kidney failure.

In a research note released Thursday, Roshwalb and his colleagues Thomas Wei and Rachel McMinn viewed favorably the U.S. label for Ventavis, calling it a "broad label" and one with "no black box warning and no bolded warning language related to [fainting]." Unlike the restricted European label, the U.S. label also does not require strong warnings for other side effects.

"Overall, we believe that the approved label will allow the company to effectively market Ventavis," the note stated.

Berlin-based Schering is serving as the exclusive manufacturer of Ventavis through its FDA-approved facility in Spain. While CoTherix has 18 sales representatives and three sales managers ready to market the product, a launch will occur early in the second quarter while the company waits for export clearance from the Spanish government.

CoTherix said it has a sufficient sales force to reach physicians who treat PAH patients.

"About 80 percent of the subscriptions are written by 500 to 600 physicians for this market, so you don't need an army of people to reach them," said Thomas Feldman, CoTherix's president and chief business officer. "We'll probably be calling on 1,500 total."

PAH is characterized by high blood pressure in the pulmonary arteries of the lungs and affects about 50,000 U.S. patients, but only about 15,000 of them are diagnosed and under treatment. While the cause is unknown, it might result from diseases that cause a restriction of blood flow to the lungs, such as scleroderma, HIV and lupus. Symptoms include fatigue, shortness of breath or exertion, chest pain and dizziness. If it is not treated, the median survival time could be as short as three years.

"Currently, when patients are diagnosed, it would be typical that they would be started on an endothelin receptor antagonist," Santel said. "And we know that 30 percent to 50 percent that are on this approved drug need augmentation from another class."

Ventavis, a member of the prostacyclin class, could fill the gap and provide a less-invasive alternative to current prostacyclins that are intravenously or subcutaneously delivered. Such treatments require the surgical implantation of a catheter or they cause significant painful site reactions, so severe that "a third of patients in the pivotal trial required narcotics," Santel said.

Tracleer (bosentan), the approved endothelin receptor antagonist used to treat PAH, is made by Allschwil, Switzerland-based Actelion Ltd. CoTherix is studying Ventavis in combination with Tracleer in a 60-patient Phase II study, which started in June.

"A good endothelin and augmenting it with a prostacyclin is a concept that physicians speak to us about constantly," Santel said.

Ventavis is administered through a nebulizer and one treatment takes about 10 minutes.

"Within one month after starting this therapy, the patients have a significant improvement in their exercise tolerance," said James Pennington, CoTherix's executive vice president and chief medical officer. "Some of these patients actually feel and perform better sooner than one month."

The NDA was based on a randomized, double-blind, placebo-controlled trial conducted in 203 adult patients. The primary endpoint was measured by an improvement in NYHA functional class, an increase in the distance walked in six minutes of at least 10 percent, and no clinical deterioration or death. Patients treated with Ventavis had a 19 percent response rate, compared with a 4 percent rate in placebo-treated patients (p=0.0033). The six-minute walk distance measured 30 minutes after inhalation was greater in the Ventavis group at all time points, including week 12, even with a placebo-corrected difference of 40 meters (p<0.01).

As part of the licensing agreement, CoTherix was responsible for regulatory fees and U.S. clinical trials, and it will pay Schering an undisclosed royalty. The approval of Ventavis triggered a $9 million payment to Schering, which originally was to be paid within 30 days, but CoTherix attained a six-month deferral, said Christine Gray-Smith, the company's executive vice president and chief financial officer.

As of the end of the third quarter, the company had pro-forma $47 million in cash, which included proceeds from the October initial public offering that raised $30 million. (See BioWorld Today, Oct. 18, 2004.)

The cash balance will carry CoTherix through the fourth quarter of 2005, Gray-Smith said.

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