E-DRUG: U.S. FDA Clears New T.B. Drug

[srahmad@essential.org]

E-DRUG: U.S. FDA Approves New T.B. Drug in 25 Years
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T98-37                         
June 23, 1998                  
                              
         FDA CLEARS TUBERCULOSIS DRUG FOR MARKETING

FDA granted accelerated approval yesterday of a new drug for pulmonary 
tuberculosis, making it the first drug approval for this indication in 
25 years and making the United States the first country to approve this 
new therapy. Rifapentine will be marketed for use in combination with 
other anti-tuberculosis agents that help to treat pulmonary 
tuberculosis. The following can be used to answer questions:

Worldwide, tuberculosis remains the most frequent infectious disease to 
cause morbidity and death. The World Health Organization estimates that 
there will be 90 million new cases of tuberculosis and 30 million 
deaths worldwide caused by tuberculosis in the 1990's. Pulmonary 
tuberculosis, the most common form of tuberculosis (TB) in the United 
States, can be a highly contagious, life-threatening lung infection. 
According to the Centers for Disease Control, approximately 19,000 new
cases of tuberculosis were diagnosed in the United States in 1997, and 
the health care community has had serious concerns about the 
development of drug resistance.

Clinical studies on rifapentine compared the drug to standard therapy, 
evaluating the drug predominantly in patients in South Africa. The drug 
was studied in combination with three other drugs: isoniazid, 
pyrazinamid and ethambutol. These same drugs were used in the other arm 
of the trial that treated patients with an approved anti-tuberculosis 
agent similar to rifapentine: rifampin. Ultimately, the drugs appeared 
to treat patients comparably, but in follow-up, there was a 10 percent 
rate of relapse in rifapentine patients compared to a 5 percent rate in 
rifampin patients.

In May 1998, FDA's Antiviral Drugs Advisory Committee recommended the 
agency approve this drug, despite the higher relapse rate because:

Patients are more likely to comply with the obligations of the therapy 
because the drug regimen is easier to follow; standard therapy has 
historically involved two months of rigorous, daily treatment, followed 
by another four months of twice weekly treatment. Rifapentine therapy 
for the first two months has a similar dosing schedule (daily 
isoniazid, pyrazinamide, ethabutol and twice weekly rifapentine). 
However, in the second course of therapy, patients' dosing schedule is 
weekly (rifapentine plus isoniazid) rather than twice weekly (rifampin 
plus isoniazid). For compliance reasons, many tuberculosis patients must 
undergo "directly observed therapy," requiring office visits for each 
course of treatment, so a reduction in dosing should improve patient
compliance. 
     
Better compliance not only improves patient outcomes, but should deter 
drug resistance, which has been associated with antibiotics. 
     
While the relapse rate with rifapentine was higher than that of 
rifampin, neither were alarmingly high (10 percent to 5 percent). 

Rifapentine's safety profile appears to be similar to rifampin. 
Patients and health care providers should be watchful for increased 
liver enzyme levels which can be a precursor to liver damage and 
increased uric acid levels, which can be a precursor to gout. One of 
the most common side effects is discolored, orange-reddish urine.

Marion Merrell Dow of Kansas City, Missouri, will manufacture 
rifapentine under the trade name Priftin. Because pulmonary
tuberculosis affects a relatively small population of patients in the 
United States, rifapentine has been designated as an orphan
drug. Orphan drug status guarantees the developer of an orphan product 
seven years of market exclusivity for the orphan drug indication 
following FDA's marketing approval, and provides other financial 
incentives for drug development.

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