Tracleer and PPH News
FDA Clears Way for New PH Drug
by John C. Martin
06-09-05 - People with pulmonary hypertension now have a new treatment option at their disposal. The U.S. Food and Drug Administration has approved the drug Revatio, known by its generic name sildenafil citrate, for pulmonary arterial hypertension, says its manufacturer, Pfizer.
Sildenafil citrate is actually the active ingredient in Viagra—Pfizer's medication that it says is used by 26 million men around the world for erectile dysfunction.
Clinical Development History
"Pfizer undertook a 6-year clinical development program in pulmonary arterial hypertension because patients with this devastating disease needed more medical options, and there was evidence that sildenafil could be an effective treatment," said Joe Feczko, MD, President of Worldwide Development and Vice-President of Global Research and Development at Pfizer, in a statement.
The FDA had granted the medication priority review status, an expedited review process for investigational medications that may address unmet medical needs. According to Pfizer, the government agency's approval hinged on a pivotal randomized, double-blind, controlled clinical study involving 277 patients with pulmonary arterial hypertension. Patients were assigned at random to one of three doses of Revatio three times daily or doses of placebo for the same frequency. Researchers then measured the exercise capability of each patient after 12 weeks of therapy.
Drug Demonstrates Efficacy
At the end of the study, those receiving the doses of Revatio showed highly significant improvements in the distance they were able to walk in 6 minutes compared to those consuming a placebo, Pfizer stated. They also showed improvements in their pulmonary artery blood pressure and other measures of heart function in the study. A 1-year placebo-controlled extension trial was also conducted. At its conclusion, the researchers reported that exercise capacity and walking distance were stable in each of the patients who took part, and 94 percent were still alive.
Since no differences in effectiveness were seen between the three dosage groups in the original trial, the drug will be prescribed at the minimum dose used in the trial—20 mg three times per day, Pfizer reported.
A First
The company says its medication will be the first oral therapy for people with early stages of pulmonary hypertension. It is indicated for the treatment of PH to improve exercise ability. Pfizer says the drug has yet to be evaluated in patients currently taking Tracleer (bosentan), manufactured by Actelion Pharmaceuticals as an oral therapy to improve exercise ability in later-stage pulmonary arterial hypertension.1 However, a preliminary European study examining the effectiveness of Revatio and Tracleer reported that the combination may be safe and effective for people with the illness.2
In studies on Revatio, the most common side effects reported were headache, indigestion, flushing, nosebleed, and insomnia, Pfizer stated.
The company says it expects to make the drug available to patients by mid-July.
1. PH Neighborhood. Tracleer: Endothelin Receptor Antagonist. Available at: http://www.phneighborhood.com/content/treatment_options/
medications_for_ph_1643.aspx. Accessed June 9, 2005.
2. Hoeper MM, Faulenbach C, Golpon H, Winkler J, Welte T, Niedermeyer J. Combination therapy with bosentan and sildenafil idiopathic pulmonary arterial hypertension. Eur Respir J 2004 Dec;24(6):1007-10.
John Martin is a long-time health journalist and an editor for Priority Healthcare. His credits include overseeing health news coverage for the website of Fox Television's The Health Network, and articles for the New York Post and other consumer and trade publications.
UPDATE: Docs Release More Findings in PH Drug Trial
by John C. Martin
06-09-05 - Researchers at a California medical conference last month unveiled more findings of a pivotal Phase 3 clinical trial testing the safety and efficacy of an investigational medication for pulmonary arterial hypertension.1 The trial is one of the bases for a pharmaceutical manufacturer's move to seek approval of the drug from the U.S. government.
A Hidden Cause
Pulmonary hypertension is a rare lung disorder in which the blood pressure in the pulmonary artery—which runs from the heart to the lungs—rises far above normal levels. The reason is still unknown. This abnormally high blood pressure, in turn, leads to abnormal changes in the small blood vessels in the lungs. Increased resistance to blood flowing through the vessels results, placing a strain on the heart's right ventricle, eventually leading to right-heart failure, and possible death. In the United States, about 500 to 1,000 new cases of primary pulmonary hypertension are diagnosed each year. More women than men are diagnosed, according to estimates, and it's most commonly found in those between ages 20 and 40.2
Comparing Thelin to Placebo
The trial, lasting 18 weeks, put the drug Thelin, also known by its generic name sitaxsentan, to the test in a group of 246 patients with the disease. The participants were assigned at random to groups receiving one of two doses of the medication, or a group given a placebo as a comparison. A group in the study also received the already approved PH drug, Tracleer (bosentan), to compare the results.
The study investigators reported Thelin improved the distance that patients were able to walk in a standard 6-minute test. This was seen particularly in those taking 100 mg doses. Their walking distance increased "significantly", according to the drug's maker, Encysive Pharmaceuticals, by an additional 31 meters (34.3 yards) versus those on placebo.
By contrast, those taking Tracleer increased their walking distance in 6 minutes by about 29 meters (32.3 yards), the study team reported. While that was also a positive finding, it was later found that starting at week 12 of the study, those taking 100 mg of Thelin continued to improve, whereas those taking Tracleer "trended down". Thelin also improved function (based on WHO criteria) compared to placebo, but Tracleer did not, the investigators noted.
Patients were also assigned 50-milligram doses of the drug, but the investigators said the findings in that group were not significant. Thus, Encysive says it doubts the drug will be made available to patients at this dose.
Encysive Seeks FDA Endorsement
"We are very pleased with the clinical results of our second-generation, selective endothelin antagonist, whether compared to placebo or to bosentan, the only approved oral product for pulmonary arterial hypertension," said Bruce Given, MD, Encysive's President and CEO, in a company press release. "Data from [this trial] and our other Phase 2 and 3 studies form the basis of our New Drug Application", which was scheduled to be filed in May.
Side effects reported in trials of Thelin include headache, edema (fluid build-up), nausea, upper respiratory tract infection, dizziness, insomnia, nasopharyngitis, and nasal congestion.3
1. ATS 2005. The International Conference of the American Thoracic Society. 2005 May 20-25. San Diego, CA.
2. American Heart Association. Primary or Unexplained Pulmonary Hypertension. Available at: http://www.americanheart.org/presenter.jhtml?identifier=4752. Accessed June 9, 2005.
3. Barst RJ, Langleben D, Frost A et al. Sitaxsentan therapy for pulmonary arterial hypertension. Am J Respir Crit Care Med 2004 Feb 15;169(4):441-7. Epub 2003 Nov 20.
John Martin is a long-time health journalist and an editor for Priority Healthcare. His credits include overseeing health news coverage for the website of Fox Television's The Health Network, and articles for the New York Post and other consumer and trade publications.
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