Protease Inhibitor: Roche Lottery Deadline July 21


In a widely distributed June 21 press release, Hoffmann-La
Roche announced details of "The Invirase* International
Compassionate Treatment Program." This program will distribute
saquinavir (brand name, Invirase), a protease inhibitor, to
persons with a CD4 (T-helper) count under 300 who no longer
benefit from approved antiretroviral drugs (AZT, ddI, ddC, and
d4T), and meet other entry criteria. Roche not only allows, but
even encourages, combination use of its protease inhibitor
together with the approved antiretrovirals. 60 percent of the
slots will be reserved for persons with a T-helper count under
50. [Note: Roche uses the spelling "proteinase," instead of
"protease." The meaning is the same.]

The drug will be made available to 2,280 patients in the
U.S., 96 in Canada, and about 1700 in Europe and Australia; Roche
has set up a lottery in case more people apply for the drug. To
get into the first U.S. lottery drawing, your physician must
enter you on or before July 21, 1995. (When more drug is
available, another lottery will be conducted, including those not
selected from the first lottery, and others who apply later.
Therefore, if you miss this deadline, you can still apply for a
possible subsequent lottery.)

To get details about this program, you or your physician can
call 800/332-2144, Monday through Friday between 9:00 a.m. and
8:00 p.m. Eastern time. You can also request information by fax,
800/332-7644; or by mail, by sending a written request for
information to the Roche Data Coordinating Center, P. O. Box
81312, Wellesley Hills, MA 02181. [In Canada, the program is
slightly different; call 800/257-3741 for Canadian information.]

Comment

We have not been greatly impressed by the previous data we
have seen on saquinavir, at the doses which will be used in this
program. The drug seems to be safe, and to be effective; but the
average size of the effect is not that great, unless larger doses
are used. However, some individuals do seem to benefit much
better than the average. And new data from Roche (see below) may
make saquinavir a better drug, by showing doctors how to use it
more effectively. It is too early to judge this drug.

There have been concerns that people who use saquinavir
alone are likely to develop resistance to it, which may cause
cross-resistance to other protease inhibitors. If this happens,
it could mean that people who use an early protease inhibitor
might lose the ability to benefit not only from that drug, but
also from better protease inhibitors which may be available in
the future. This issue has been controversial among experts; for
example, Roche's experts and Merck's experts have disagreed about
it. Now Roche claims that new data, to be released July 10 at
the Fourth HIV Drug Resistance Workshop in Sardinia, Italy --
data on almost 100 people, compared to the four to six people
that Merck tested -- indicates that saquinavir does not cause
resistance to other protease inhibitors -- and that the
development of resistance to saquinavir itself can be reduced by
using that drug in combination with AZT. Over the next few weeks,
we will see how this new information is evaluated by the medical
community, and by scientists independent of both companies.

It is also important to realize that different people have
very different individual responses to AIDS treatments. For some
people, this drug works much better than it does on the average.
One argument in favor of trying saquinavir is to see if it works
exceptionally well for you.

What if you cannot decide whether or not to apply for the
lottery program, and cannot get an appointment with your doctor
before the deadline? One strategy is to call and ask your doctor
to apply anyway -- it is easy for the doctor to do, requiring
only a simple form and a copy of a T-cell test from your medical
records. Everything can be handled by fax. Also, you can start
the whole process on your own, by calling the phone number above
to get information about the program, and advice on getting your
doctor to enter you.

Later, if you are accepted, there will still be some time
before you actually get the saquinavir; and you can use this time
to meet with your doctor decide whether or not you want to use
the drug.

We will be surprised if Roche gets 2280 U.S. applicants for
this lottery by July 21. There just isn't enough time for the
word to get around, for over 2,000 people to hear about the
program, grasp the information, see if they qualify, decide if
they want the drug at all, make doctors appointments, talk with
their physicians, and get the forms turned around, all between
the first detailed press release on June 21, and the lottery
cutoff on July 21.

On July 5 Roche told us that they were optimistic on filling
the program, as they had 5,000 phone calls after articles were
published in The Wall Street Journal and other newspapers; and
they had several hundred completed applications as of July 3.
Even so, we still doubt that they will get 2280 qualified
applications by July 21. If they do not, this means that no
lottery will be needed, since all qualified applicants who apply
by that deadline will get into the program. And there may also
be extra slots for people who apply after July 21; however, we
are not sure about this.

But on the negative side, failure to fill the lottery in one
month might be wrongly interpreted as lack of public interest in
expanded access, protease inhibitors, or new AIDS treatments,
when in fact the obvious obstacles listed above would be
responsible. We believe that the expected inability to fill all
slots immediately could have been predicted even before the
program was announced. Even under the best circumstances it is
hard to inform the public and get people to change their
behavior. This program has to get over 2,000 specially qualified
patients and doctors to change their behavior together, to follow
a new procedure to get an experimental drug that even the doctors
do not know much about, all within one month after receiving a
form letter or reading an article in a newspaper.

[Note: There is also a completely separate program for
access to the Merck protease inhibitor best known as MK-639 (it
has now been given the chemical name indinavir sulfate, and the
brand name Crixivan*); many third-party observers consider this a
more promising drug than low-dose saquinavir. The Merck program,
which will begin in August or September, will provide MK-639 to
1400 people who have a CD4 count below 50 and meet other entry
criteria. Information about this program will be announced by
Merck, probably in July.]