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Primary Arterial Hypertension News - Menu
FDA News
FOR IMMEDIATE RELEASE
P07-104
June 15, 2007
Media Inquiries:
Sandy Walsh, 301-827-6242
Consumer Inquiries:
888-INFO-FDA
FDA Approves New Orphan Drug for Treatment of Pulmonary Arterial Hypertension
The U.S. Food and Drug Administration (FDA) today approved Letairis (ambrisentan) for the treatment of pulmonary arterial hypertension, a rare, life-threatening condition characterized by continuous high blood pressure within the arteries of the lungs.
"Letairis represents a valuable addition to the treatment alternatives for this orphan disease," said John Jenkins, M.D., director of FDA's Office of New Drugs. "Letairis is similar to an existing drug, but offers the potential for fewer drug interactions."
In pulmonary arterial hypertension, the small arteries in the lungs become narrowed or blocked, and the heart must work harder to pump the blood through them. Over time, the overworked heart muscle may become weak and lose its ability to pump enough blood through the lungs. Symptoms include shortness of breath, fatigue, chest pain, dizzy spells and fainting. About 100,000 people in the United States have pulmonary arterial hypertension.
Letairis, a new drug not previously approved in the United States, was granted a priority review by FDA. A priority review designation is intended for those products that address unmet medical needs. For priority drug applications, FDA sets a target date of six months after the date of receipt for the agency to complete all aspects of a review and to take action.
The safety and effectiveness of Letairis were demonstrated in two international clinical trials involving 393 patients. Letairis significantly improved physical activity capacity compared with a placebo, as shown by a six-minute walk, a standard test. Letairis also delayed the worsening of the pulmonary hypertension.
The most common side effects in patients using Letairis included swelling of legs and ankles, nasal congestion, sinusitis, and getting red in the face (flushing).
Letairis should not be used by women who are pregnant or may become pregnant because the drug may cause birth defects. Patients taking Letairis must have monthly blood tests to check for potential liver injury.
Letairis will be available in five-milligram and 10-milligram once-daily tablets.
Letairis was granted orphan drug status by FDA because it treats a rare disease and meets other criteria. Orphan designation qualifies the drug's sponsor for a tax credit and marketing incentives.
Letairis is manufactured by Gilead Sciences, Inc., Foster City, Calif. Gilead acquired the U.S. rights to ambrisentan when it acquired Myogen, Inc. in 2006. GlaxoSmithKline holds rights to ambrisentan outside of the United States.
For more information:
The Orphan Drug Act
www.fda.gov/orphan/
National Heart Lung and Blood Institute – What is Pulmonary Arterial Hypertension?
www.nhlbi.nih.gov/health/dci/Diseases/pah/pah_what.html
INDICATION: LETAIRIS is an endothelin receptor antagonist (ERA) indicated for the treatment of pulmonary arterial hypertension (PAH) (WHO Group 1) in patients with WHO Class II or III symptoms to improve exercise capacity and delay clinical worsening.
WARNING: POTENTIAL LIVER INJURY
LETAIRIS (ambrisentan) can cause elevation of liver aminotransferases (ALT and AST) to at least 3 times the upper limit of normal (ULN). LETAIRIS treatment was associated with aminotransferase elevations >3 x ULN in 0.8% of patients in 12-week trials and 2.8% of patients including long-term open-label trials out to one year. One case of aminotransferase elevations >3 x ULN has been accompanied by bilirubin elevations >2 x ULN. Because these changes are a marker for potentially serious liver injury, serum aminotransferase levels (and bilirubin if aminotransferase levels are elevated) must be measured prior to initiation of treatment and then monthly.
In the post-marketing period with another endothelin receptor antagonist (ERA), bosentan, rare cases of unexplained hepatic cirrhosis were reported after prolonged (>12 months) therapy. In at least one case with bosentan, a late presentation (after >20 months of treatment) included pronounced elevations in aminotransferases and bilirubin levels accompanied by non-specific symptoms, all of which resolved slowly over time after discontinuation of the suspect drug. This case reinforces the importance of strict adherence to the monthly monitoring schedule for the duration of treatment.
Elevations in aminotransferases require close attention. LETAIRIS should generally be avoided in patients with elevated aminotransferases (>3 x ULN) at baseline because monitoring liver injury may be more difficult. If liver aminotransferase elevations are accompanied by clinical symptoms of liver injury (such as nausea, vomiting, fever, abdominal pain, jaundice, or unusual lethargy or fatigue) or increases in bilirubin >2 x ULN, treatment should be stopped. There is no experience with the re-introduction of LETAIRIS in these circumstances.
CONTRAINDICATION: PREGNANCY
LETAIRIS is very likely to produce serious birth defects if used by pregnant women, as this effect has been seen consistently when it is administered to animals [see Contraindications (4.1)]. Pregnancy must therefore be excluded before the initiation of treatment with LETAIRIS and prevented thereafter by the use of at least two reliable methods of contraception unless the patient has had a tubal sterilization or Copper T 380A IUD or LNg 20 IUD inserted, in which case no other contraception is needed. Obtain monthly pregnancy tests.
Because of the risks of liver injury and birth defects, LETAIRIS is available only through a special restricted distribution program called the LETAIRIS Education and Access Program (LEAP), by calling 1-866-664-LEAP (5327). Only prescribers and pharmacies registered with LEAP may prescribe and distribute LETAIRIS. In addition, LETAIRIS may be dispensed only to patients who are enrolled in and meet all conditions of LEAP [see WARNINGS, Prescribing and Distribution Program for LETAIRIS].
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