Saquinavir (Invirase): First Protease Inhibitor Approved -- Reimbursement, Information Hotline Numbers

Saquinavir (brand name Invirase(TM)), developed by Hoffmann- La Roche, was approved by the FDA on December 6, and is currently available in pharmacies. It is the first of a new class of anti-HIV drugs, called protease inhibitors, to be approved for marketing. AIDS TREATMENT NEWS already covered some technical aspects of this drug in two articles in issue #235, November 17, 1995: "Protease Inhibitors: Drug Resistance and Cross Resistance," and "Grapefruit Juice and Saquinavir."

Saquinavir was approved for use in combination with one or more nucleoside analog drugs, but no particular drug was specified. At this time there is no data about combining saquinavir with any nucleoside analog except AZT or ddC. It is likely that physicians will favor AZT for previously- untreated patients, favor ddC for patients already extensively treated with AZT, and also try saquinavir in combination with other antivirals.

Saquinavir does not cross the blood-brain barrier.

Saquinavir should not be used at the same time as rifampin, which decreases saquinavir blood concentrations by 80% -- and used cautiously if at all with rifabutin, which decreases saquinavir concentrations by 40%. Other potentially important drug interactions are described in the saquinavir package insert (the prescribing information for physicians).

The recommended adult dose is three 200-mg capsules taken three times daily, within two hours after a full meal. Lower doses are not recommended, since they have not shown antiviral activity. There is no data on the pharmacokinetics, safety, or efficacy of saquinavir in persons under 16.

Price and Reimbursement Help

The price of saquinavir to wholesalers is $15.89 per day ($5800 per year); retail prices will be higher because they include the markups of the wholesaler and the pharmacy.

Hoffmann-La Roche has suggested that no one will fall through the cracks: "To ensure that every patient in the U.S. who can benefit from Invirase(TM) gets immediate and sustained access to the drug, irrespective of their financial situation, Roche has established the Roche HIV Therapy Assistance Program. This important program will make supplies of Invirase(TM) available to patients who are waiting to be approved for coverage and reimbursement through their existing insurance sources, and to patients who are uninsured and cannot afford to pay for the drug." (Press release, December 7). This assistance program will provide information about coverage for the drug, help callers apply for insurance (including helping with denied or underpaid claims, and with appeals), and screen and enroll eligible patients in the Medical Needs Program for those without insurance or financial means.

For more information, patients and health-care providers in the U.S. can call the Roche HIV Therapy Assistance Program, 800/282-7780 (or 202/942-2437), Monday through Friday 9:00 a.m. to 8:00 p.m. Eastern time.

Information for physicians about saquinavir and other Roche products is available at 800/526-6367. The number for patients and customers to call is 800/910-4687.

Comment

The protease inhibitor class of drugs is indeed important; early results suggest that in the right doses and combination regimens, they may work very well. But despite the hype in some media reports, the observed signs of benefit from the low dose of saquinavir now recommended have been modest. T- cell increases and viral load reductions have been more or less comparable to those of AZT. The problem seems to be that saquinavir is now being used at the bottom of its dose- response curve; a new formulation, now being tested by Roche but not yet available, may deliver more effective amounts.

Since average blood levels of saquinavir are minimally adequate for antiviral activity, and individuals may vary in how well they absorb the drug, it is possible that the current dose may work well for some people. But we do not know this, as the package insert only gives group averages of CD4 and viral load responses, not information on how these varied among individuals. Also, as our last issue suggested, grapefruit juice may increase blood levels of saquinavir -- although there is no blood-level test available to tell if this is working for you. Patients may want to get a viral load test before starting saquinavir, so that they can later get some estimate of how well the drug is working for them.

One overlooked factor that may increase future use of protease inhibitors is that a number of people who have been completely opposed to AZT and other nucleoside analogs do not feel the same way about these new drugs. The objection often was to nucleoside analogs in particular -- not to all high- tech anti-HIV drugs. Today, the great majority of people with HIV, even in the U.S., are not receiving any specific treatment for it; this could change if newer drugs continue to look promising -- provided that ways can be found to pay for them.

Concerning the price, no one outside of Roche knows if it is a fair one, as no one knows the development and manufacturing costs of the drug. Manufacturing costs are believed to be substantial; and there is concern that if pharmaceutical companies keep losing money on AIDS, they will not develop important new drugs such as integrase inhibitors. But the increasing total cost of AIDS medications is a major problem, especially as standard of care changes from one drug (AZT) to combinations of two or three. This would still be a major problem even if saquinavir were at half its current price.

One possible approach to the cost problem is a strategy of harm reduction -- reducing the harm caused by the high cost. This strategy could start by analyzing how the drugs are actually being paid for, and who is being left out. Roche has come close to saying that no one in the U.S. will be left out (see quote above); we should monitor the Roche HIV Therapy Assistance Program to see how well it accomplishes this stated goal. The next step is to focus on remaining problems, looking at all possible means -- public assistance, private insurance, better targeting and timing of treatments, outcomes research, disease management, price reductions, alternative drugs, etc. -- to make adequate treatment available.