Following receipt of an approvable letter from the FDA, United Therapeutics Corp. said its orphan drug for pulmonary arterial hypertension should reach the market sometime in the next two months.
Final approval of Remodulin (treprostinil sodium) is expected well before completion of a government-required post-marketing controlled clinical trial aimed at verifying and further describing the drug’s clinical benefit, the company said. Remodulin formerly was referred to as UT-15 and Uniprost.
Fred Hadeed, chief financial officer of United Therapeutics Corp. (UTC), located in Silver Spring, Md., told BioWorld Today that approval is likely to come once the company and FDA agree on language in the label and the design of the Phase IV trial.
The company’s stock (NASDAQ:UTHR) closed Monday at $11.10, up $1.66, or 17.6 percent.
In a conference call with investors and analysts Monday, Martine Rothblatt, UTC’s CEO, said, “This is a goal that the company has been diligently working toward for over five years. We are extremely appreciative of the FDA, the patients and the clinicians who worked with us, that we have been able to develop a substantial enough database to be rewarded by the FDA with this approvable letter. It is a tremendous testament, I believe, to the ability of the U.S., in particular, the free enterprise system, to work together with the medical community, the patient community and the government, as the regulators and watchdogs over the entire process, to produce a result which is in everybody’s best interest.”
Remodulin, a subcutaneously administered prostacyclin analogue, will be indicated for pulmonary arterial hypertension (PAH) consistent with the treatment of both primary and secondary pulmonary hypertension in patients with NYHA (New York Heart Association) Class II through Class IV symptoms.
People suffering with PAH, a life-threatening condition, have reduced levels of prostacyclin within the blood vessels in their lungs, resulting in dizziness, fainting, diminished exercise ability and potentially right-heart failure.
UTC estimates that there are 50,000 people in North America and Europe who suffer from forms of the condition, and only 5,000 have been diagnosed.
Treatment options in the last few years have been limited to either a lung transplant or GlaxoSmithKline’s intravenous therapy called Flolan (epoprostenol).
But in recent months, Actelion Ltd., of Allschwil, Switzerland, won FDA approval of Tracleer (bosentan) in PAH patients with Class III or Class IV symptoms.
The indication is a little different, said Hadeed, who characterized Remodulin’s indication as “broad.”
“We have a broader label than Tracleer and Flolan,” Hadeed said. “There are markets we can operate in that they are not legally allowed to operate in.”
Vandana Bapna, a biotechnology equity analyst with Offutt Securities in Cockeysville, Md., said based on the price of Flolan, Remodulin likely will sell for $50,000 per year per patient. By the end of next year, she said, UTC should have about 1,200 U.S. patients on the product.
The company has not received European approval yet, but Hadeed said France is expected to grant approval very soon.
Asked in a conference call how common it is for the FDA to require a Phase IV trial, Roger Jeffs, UTC’s president and chief operating officer, said, “I think in general most drugs have some sort of additional work to be done, whether that is drug interaction work, there’s often many things companies need to follow up on. I think we’ll have an approval letter in coming months for Remodulin.”
In earlier clinical trials, Jeffs said, UTC looked at the patient’s ability to walk during a six-minute test and the patient’s shortness of breath (after the test). “Obviously, those two things are related in linked measurements. We did not prospectively link those measurements but retrospectively did.
“I think the true strength of Remodulin is identified in the linking of those measurements and that is patients walked further and they did so with less shortness of breath, and the agency in their letter has expressed that that was a meaningful outcome and probably is predictive of the clinical benefits although it was not done prospectively,” Jeffs said. “So one of the potential things we could do in a post-approval setting is we could validate that prospectively.”
The FDA’s Cardiovascular and Renal Drugs Advisory Committee last summer voted 6 to 3 recommending approval of Remodulin. (See BioWorld Today, Aug. 10, 2001.)
The committee reviewed UTC’s two Phase III studies that evaluated the change in exercise capacity as measured by distance walked in six minutes. At issue among committee members was UTC’s failure to meet its primary endpoint, which required participants to be able to walk 55 meters after 12 weeks of dosing. At the close of the trials, patients were able to walk 10 meters.
UTC submitted its new drug application for Remodulin on Oct. 16, 2000, and received six-month priority review status, requiring FDA action no later than July 16, 2001. Initially, an advisory committee meeting to hear the application was scheduled Feb. 9, 2001, but in mid-December 2000, the FDA informed the company that a hearing would not be necessary. A meeting was later rescheduled for Aug. 9, 2001. (See BioWorld Today, Dec. 18, 2000, and Aug. 10, 2001.)
In October, UTC’s beraprost failed to meet its endpoints in a trial in peripheral vascular disease patients. The company said it abandoned plans for the drug for intermittent claudification (pain when walking). It is in Phase III trials for PAH, data from which was expected to be available in the second quarter. (See BioWorld Today, Oct. 16, 2001.)