PI Perspective #23

November 1997     View PDF     En español

Expanded Access Programs Expanding

Three new drugs are currently available in expanded access programs—abacavir (formerly known as GW1592), adefovir (Preveon, formerly known as bis-POM PMEA and GS 840) and efavirenz (Sustiva, formerly known as DMP-266).

Although initial programs for these drugs are very small and constrained by limited drug supplies, they will soon be expanded to provide access to a wider group of people. The first step of expanding the efavirenz program is likely to be announced by the time readers receive this issue of PI Perspective, and a final form of the program should be in place early in 1998. Expansion of the program for abacavir should also take place early in 1998.

Efavirenz
This drug is a highly potent non-nucleoside analogue reverse transcriptase inhibitor (NNRTI), the same class of drug as nevirapine (Viramune) and delavirdine (Rescriptor). Although only preliminary information is available, the drug has shown fairly remarkable activity when used in combination with indinavir (Crixivan). Additional clinical trials are studying its use in combination with a wide variety of other drugs, including AZT + 3TC, other protease inhibitors, and combinations employing one each of all three classes of drugs. Perhaps the most remarkable quality of efavirenz is that it remains stable in the body longer than almost any other currently available AIDS therapy. This quality permits the simplicity of once-daily dosing.

The initial efavirenz program was limited to people with fewer than 50 CD4+ cells with a history of failure on current regimens. The first stage expansion of the program extends the CD4+ cell limit to 200. The final stage of the program, if agreed to by the Food and Drug Administration, will eliminate CD4+ cell limits. For more on the efavirenz program call 800-998-6854.

Abacavir
This widely discussed drug, formerly known as GW1592, is a highly potent nucleoside analogue. It’s highest level of potency, however, is limited to people who have not previously used other drugs of this class. New data shows that in general, the more drugs of this type a person has previously used to the point of failure, the less likely it is that this drug will work. Thus, its role will be limited, even though it is likely to make an excellent choice for first time therapy.

The current program for abacavir is limited to people who have CD4+ cell counts below 100, a viral load above 30,000 copies HIV RNA and who have failed at least one protease inhibitor regimen. The expansion of this program in early 1998 should at the very least remove these restrictions and make the drug widely available to people who need it to build an effective combination. For information on the program call 800-501-4672.

Adefovir
This is a nucleotide analogue which blocks HIV replication at the same stage of the virus life cycle as the nucleoside analogues and is dosed once daily. Results from earlier studies show modest anti-HIV activity when used alone. It is not known how well people who have failed on existing nucleoside analogue therapy will respond to adefovir. This drug also has activity against hepatitis B virus and cytomegalovirus (CMV)—however it is unlikely that adefovir can be used to treat CMV, although it may be effective in preventing the disease.

The current program is limited to those who have CD4+ cell counts below 50, a viral load above 30,000 copies HIV RNA and who have failed or are intolerant to a combination regimen containing two nucleoside analogues and a protease inhibitor. For more on the program call 800-445-3235.

Redefining Expanded Access
All previous expanded access programs for new drugs have been a product of the older era of AIDS therapy, which supplied one new drug at a time when earlier therapies failed. Today, we know that this model is ineffective and even harmful in the sense that it wastes the opportunity to truly benefit from the new drugs. But the same old rules continue to make the new drugs available in this fashion. This year, many treatment activists, as well the some of the manufacturers, are attempting to redefine the rules of expanded access to reflect the current recommendations for treating HIV disease. The key rules of current therapy call for avoiding the use of single drug therapy, and in general to avoid adding single new drugs one at a time to a failing regimen. The old expanded access programs, in effect, encourage such improper use of therapy by limiting access only to those people who have reached some arbitrary and often dangerously low level of CD4+ cells (or high viral load), and who are failing all existing regimens. In effect, the current system provides the drug only when it is likely to be too late to be of benefit and when it can’t be used properly.

New proposals are calling for elimination of CD4+ cell and viral load limits as entry criteria for expanded access. Instead, the recommended criteria will be to make the new drugs available to anyone who needs the drug to construct a viable treatment combination, as defined in the Federal Guidelines for the Use of Antiretroviral Therapy. In addition, the proposals will strongly encourage collaboration between programs so that people who need multiple new drugs can get them at the same time. By simplifying the entry criteria to these programs, the goal is to make it easier for people and their physicians to use the new drugs wisely, at a time when the patient is able to benefit most and when the drugs can be combined with one or two other new drugs the patient hasn’t previously used.

Critics who fear that such a program might be too broad frequently don’t understand that this design still imposes limits. For example, anyone who hasn’t tried many of the available combinations would still be denied access because by definition, such people don’t really need the new drug to create a viable combination. But the new program model would not deny the new drug or drugs to anyone who has cycled through the available combinations, regardless of CD4+ cell and viral load levels.

Despite wide community support, it is not clear at the time of writing whether the FDA has sufficiently advanced its own thinking to permit this approach.

Expanded Access Program Numbers

Abacavir 800-501-4672
Adefovir 800-445-3235
Efavirenz 800-998-6845

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