American Foundation for AIDS Research, April 2004
Kristen Kresge

February 2004 — Abbott Laboratories recently announced a 400% price increase for its seven-year-old HIV drug, ritonavir (Norvir), setting off a firestorm of harsh criticism from physicians. Abbott remains resolute about the increase, but patients, clinicians, and third party providers believe this represents another instance of greedy pharmaceutical companies interested in profits above patients.

Ritonavir, the second protease inhibitor released to the market, caused severe side effects at its original recommended dose and interacted with other drugs, particularly other protease inhibitors. Clinicians soon exploited this second feature by giving patients ritonavir at lower doses to increase, or “boost,” the levels of a second protease inhibitor (see figure). In 2001, Abbott introduced the first and only boosted protease inhibitor in a single pill, Kaletra (lopinavir combined with ritonavir). Ritonavir evolved to a much smaller — but significant — component of protease inhibitor-based HIV therapy.

As its role shifted, Abbott witnessed a steep decline in ritonavir’s projected revenue stream, according to John Leonard, vice president of global pharmaceutical development at Abbott Laboratories. “You have to consider this in historical context. Norvir [ritonavir] is different from what it started out to be. Its original use has been changed to boosting. It is a pharmacokinetic booster, pure and simple,” said Leonard. The modest profits Abbott was making from ritonavir “didn’t match the benefit that the product is providing,” he added.

Before December 2003, a 100-mg capsule of ritonavir cost $1.71. Depending on the required dose — typically one or two capsules — boosting a drug with ritonavir, at most, added $1,200 a year to the cost of a protease inhibitor-based regimen. But with the 100-mg capsule’s new price tag of $8.57, this may jump to as much as $6,000 a year. Abbott partially attributes the price hike to losses incurred early while manufacturing ritonavir.

Critics believe Abbott has another motive: protecting Kaletra. Kaletra became popular with doctors because of its potency and because HIV is slow to develop resistance to this drug. Abbott itself boasts that it was the most prescribed protease inhibitor from July 2002 to February 2003. But last year two new competitors entered the market: Bristol-Myers Squibb’s atazanavir (Reyataz) and GlaxoSmithKline’s fosamprenavir (Lexiva), the prodrug formulation of amprenavir. Both drugs are more potent when combined with ritonavir and both drugs alone already cost more than Kaletra, which sells for about $8,500 a year. Boosted with ritonavir, atazanavir now costs approximately $13,000 annually, and fosamprenavir costs $13,600. Since Abbott has chosen not to raise the price of Kaletra, critics see ritonavir’s increase as a way of protecting Kaletra from the competition.

A claim Abbott quickly denies. “There are going to be some carryover effects to Kaletra. Reyataz [atazanavir] is not the driving factor,” insisted Leonard.

Ben Young, a physician in private practice in Colorado, calls Leonard’s statement about atazanavir “a transparent lie.” Young broadcast his anger through a widely circulated letter to Abbott expressing his concern about the impact Abbott’s decision will have on patients. Several of his patients have private insurers that require both a copayment and 20% of the cost of medication above an annual limit. The high cost of HIV drugs already generates substantial out-of-pocket expenses. Ritonavir’s increase may now swell expenses beyond many people’s means.

To ensure that access to ritonavir continues despite the new price, Abbott abolished the patient assistance program’s income requirement for receiving the drug for free. And for now, the higher cost of ritonavir does not affect people who receive the drug through Medicaid or the state AIDS Drug Assistance Programs (ADAPs). Medicaid restricts price increases to a yearly inflation rate of 2% to 3%, and ADAPs’ negotiated prices with each pharmaceutical company remain effective until 2005. Companies do, however, have the right to withdraw from those deals, according to Lei Chou of the AIDS Treatment Data Network in New York. Chou is most concerned about how other drug companies will respond. For instance, Bristol-Myers Squibb based atazanavir’s price on ritonavir’s old one. “We don’t know how the other companies are going to react to this news. It could have a very harmful ripple effect,” said Chou, who fears Abbott’s move will influence boosted protease inhibitors still in development.

At least four new protease inhibitors in advanced stages of development require ritonavir. Tipranavir, by Boehringer Ingelheim, is a highly anticipated therapy for treatment-experienced HIV patients but is most effective when combined with 400 mg of ritonavir (200 mg taken twice daily). At this dosage, the ritonavir alone will cost over $12,000 a year. “This could have a very harmful, immediate impact on the development of tipranavir,” added Chou. Drugs like tipranavir are already expected to cost more than other protease inhibitors. The increased costs of ritonavir boosting may drive tipranavir’s price higher than T-20’s (Fuzeon), which, at over $20,000 a year, is currently the most expensive HIV drug.

Although final pricing decisions await marketing approval, Young fears that the trend toward escalating drug prices could compromise quality of treatment. He predicts that some doctors will avoid prescribing ritonavir because of the added expense. “The vast majority of doctors using Reyataz [atazanavir] are going to use it in a boosted way,” he said, for both patients just beginning therapy and those who need more potent drugs to rescue failing drug regimens. However, if doctors fixate on a drug’s cost, “they are not being driven by the most medically sound decision,” added Young.

To prevent the compromise of patient care, HIV doctors around the country have led the charge demanding that Abbott rescind ritonavir’s price increase. The HIV Medicine Association (HIVMA), comprised of 2,600 doctors and scientists, issued a call for action soon after Abbott’s announcement. HIVMA registered concern over the escalating cost of HIV medications. “We are generally concerned about continuing upward pressure on prices as each new HIV drug is approved,” said Paul Volberding and Daniel Kuritzkes in a letter to Abbott.

Other doctors in the US, the only country affected by the announcement, have suggested unofficially boycotting Abbott. Some refuse to see Abbott sales representatives, hoping that such action will pressure Abbott into rethinking their decision. “The best we can hope is that they roll back the price increase to 200%,” said Young. Another clinician has threatened to buy ritonavir in Canada.

But Abbott has remained firm. “Norvir is what makes the HAART [highly active antiretroviral therapy] regimen work, and we need it to make a fair contribution to the overall package. Norvir has to contribute,” Leonard emphasized. He insists that Abbott needs the revenue from ritonavir sales to reformulate the drug so that it no longer requires refrigeration, a formulation that would also significantly improve Kaletra. Leonard also vows that the jump in profits will fund future research, a claim others dispute. “It’s widely known that Abbott has withdrawn from HIV and is not returning this money to drug research,” said Young.

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