Atovaquone (Mepron; 566C80) Approved for Pneumocystis; Drug Development, Activism Success

On November 25, the U. S. Food and Drug Administration
approved atovaquone (brand name Mepron; formerly known as 566C80)
for mild to moderate pneumocystis, as a second-line treatment for
those patients who cannot tolerate the existing treatment,
trimethoprim/sulfamethoxazole (TMP/SMX). The drug should be in
pharmacies throughout the U. S. by early December. At the same
time, Canada's Health Protection Branch also approved atovaquone
-- the first time a drug has undergone a joint, integrated review
by the two agencies.

Atovaquone was approved for second-line not first-line
treatment because a major comparative trial found that TMP/SMX
worked better for those who could tolerate it; overall the two
drugs had about the same "therapeutic success" (defined as
sustained improvement over four weeks without having to
discontinue the medication), but TMP/SMX had higher survival
after eight weeks, 97 percent vs. 92 percent for atovaquone in
that trial. However, 20 percent of those given TMP/SMX had to
discontinue its use because of side effects; now atovaquone is
available as second-line treatment for such patients. (Another
trial found that atovaquone worked about as well as injected
pentamidine, the existing second-line treatment, but had far
fewer side effects serious enough to require drug
discontinuation.)

It is important to take atovaquone with meals, because in
its current formulation at least, the drug is much better
absorbed when taken with food.

Burroughs-Wellcome, atovaquone's developer, announced a
price to the wholesaler of $2.13 per 250 mg. tablet. The
recommended dose is 2250 mg. per day (three tablets three times
a day with meals) for 21 days, meaning that the wholesale price
to treat one case of pneumocystis is about $402. (It is
difficult to give a retail price, since markups by pharmacies can
vary greatly.) Burroughs-Wellcome has announced a program to cap
the annual cost for patients without third-party coverage who use
more than 411 grams in a calendar year -- about $3500 wholesale.
This cap may alleviate some cases of hardship, although
presumably few will reach the limit. Burroughs-Wellcome also has
other programs for providing drugs to patients with financial
difficulties.

Development History, Activist Involvement

Atovaquone went from human trials to FDA approval in a
remarkably short time. Yet during this time, Burroughs- Wellcome
conducted the largest controlled trial yet of a pneumocystis
treatment, at 37 sites in the U. S., Canada, and Europe. And
while the trials were continuing, the company provided atovaquone
without charge to over 900 patients who had no other treatment
option, through a "treatment IND" approved by the FDA. Credit
belongs to Burroughs-Wellcome, the FDA, and also to AIDS
activists, especially in ACT UP/Boston, who have done much to
expand access to this drug.

The following is from a press statement released by David
Peck of ACT UP/Boston after the approval of atovaquone:

"Atovaquone's approval today represents a quantum leap in
AIDS drug development -- cooperation between activists,
government, and industry, large-scale access during early
development (which should be the rule rather than the exception),
and the sheer speed of the approval process...

"ACT UP knocked on Wellcome's door 18 months ago, and asked
for access to atovaquone during its development. Our agenda
specified drug access guidelines, such as: the target patient
population, 24-hour drug delivery, an 800 number, etc., and
Wellcome implemented this expanded access program with FDA
approval a year ago. Over 900 people got atovaquone free of
charge during the program -- and ACT UP/Boston is proud of this
accomplishment.

"ACT UP/Boston applied constant pressure on the FDA to move
this drug through the approval process. This included my
testimony to the FDA antiviral drug advisory committee, which
voted unanimously in September to recommend approval. As
recently as last week, at our urging, the FDA changed the
proposed labeling on atovaquone to make its use more inclusive...

"Atovaquone proves that ACT UP and drug companies, despite
our differences and our seemingly endless demands, can work
together. For now, our role is key: we provide the power lines
to carry community concerns to drug companies. If others in the
industry are tired of our screaming, they can take lessons from
the Wellcome of the 90s -- and put the pressing needs of the
community at the top of their drug development agenda.
Atovaquone's success proves how well this works."