American Foundation for AIDS Research, November 2003
Kristen Kresge

The year of the goat: not quite. According to Roche, 2003 is the “year of Fuzeon.” The first in a new class of AIDS drugs debuted in March and three months later at July’s International AIDS Society conference in Paris, Fuzeon was seemingly everywhere. Each day crowds of conference attendees gathered to hear the intricacies of the new medicine and watch Roche representatives inject Fuzeon into citrus fruits. Few conference sessions failed to mention the drug’s impact on HIV treatment, but so far this attention has not translated into a dramatic surge in Fuzeon sales.

Roche, with assistance from the media, hailed Fuzeon (also known as T-20 or enfuvirtide) as a drug that would revolutionize salvage therapy, and big things were expected. As the first HIV entry inhibitor, Fuzeon provides a new option for people whose virus is resistant to many antiretroviral drugs used to treat HIV. Yet Fuzeon has drawbacks—it requires twice-daily injections, resistance to it can develop in the absence of other potent drugs, and it is the most expensive antiretroviral on the market.

Despite the fanfare in Paris, the only new data released on Fuzeon were 48-week findings from the TORO studies (the two large clinical trials that led to the drug’s approval) and an analysis of what predicted success with Fuzeon at 24 weeks. Not surprisingly, these factors were a higher CD4 count and lower viral load at the start, prior exposure to fewer antiretrovirals, and more active drugs in addition to Fuzeon (abstract #116). The 48-week data demonstrated that the response at 24 weeks was generally sustained through one year (abstract #LB2).

These results also confirmed that Fuzeon is least effective in people with resistance to all other drugs, but more useful in those who can combine it with new active drugs to which their virus has not developed resistance. Without any other active drugs in their regimens, only 8% of people in the TORO trials had a viral load less than 400 copies/mL through 48 weeks. With just one other drug, the amount of people with viral loads below 400 copies/mL jumped to 29%.

“A Weak Launch”

Roche and Trimeris, codevelopers of the drug, had expected early demand for Fuzeon would quickly deplete original supplies, which were limited due to the complexity of the manufacturing process. Roche even set up a centralized prescription system to ensure that people who were prescribed Fuzeon would have an uninterrupted supply of the drug. But three months after the first shipments, the projected rush to access the new drug has not materialized. Between its approval in March and the end of June, only 2,250 new people began taking Fuzeon as part of their HIV therapy.

Limited use of the drug resulted in sluggish sales; Trimeris reported only $4.3 million in sales of Fuzeon in the second quarter of this year. These low numbers are even more striking given the extensive publicity surrounding this drug’s approval. Yet the promotional efforts of Roche and Trimeris have not resulted in a boost in prescriptions. One investor told the Wall Street Journal that the launch of Fuzeon was rather weak.

Roche remains confident that it can sell Fuzeon. “It’s not a surprise at all for us. Our feeling is that it’s tracking quite nicely,” said Heather Van Ness, a Roche spokesperson. Roche recently expanded its manufacturing capacity in the expectation that demand for Fuzeon will grow. In mid-July, Roche even raised its estimate for annual sales of Fuzeon. Van Ness suggests that as more doctors become comfortable prescribing the drug, sales will steadily increase. “It’s the first injectable antiviral in the HIV arena. There certainly is a potential for an expanded uptake. At first, physicians were prescribing it carefully just to get experience with the drug,” said Van Ness.

Traditionally, doctors gain experience with new drugs before approval through involvement in clinical trials or manufacturer-sponsored expanded access programs, which provide drug to those who need it but were excluded from trials. Prior to Fuzeon’s approval, only 250 doctors in the US were supplying Fuzeon to the approximately 1,600 people taking the drug, including 1,000 in the two TORO studies. An additional 600 people had enrolled in the early access program, an unusually low number dictated by limited drug supply.

By the end of June, about 1,000 doctors had prescribed Fuzeon for at least one of their patients, according to Van Ness. Such an increase would seem to contradict Roche’s suggestion that physicians’ willingness to prescribe Fuzeon posed a barrier to expanded use.

In fact, the 2,250 new people taking Fuzeon represent only half of those that currently want the drug, according to Roche’s data. An equal amount, as of June 30, were trapped somewhere in reimbursement limbo, waiting to arrange payment for the exorbitant cost of the drug—the average wholesale price of Fuzeon in New York is $25,334.

For those who cannot pay full price and lack private insurance, access to Fuzeon requires going through a government payer or Roche’s patient assistance program, which can provide free drug to people ineligible for state programs. At the end of June, only 250 people had qualified to receive Fuzeon through the patient assistance program.

Everyone else relies on Medicaid or State AIDS Drug Assistance Programs (ADAPs). Though state Medicaid programs and about half of the ADAPs will reimburse the cost of Fuzeon, the process of securing reimbursement is a bumpy road. Each state has different restrictions on approving reimbursement requests and every prescription requires individual verification due to Fuzeon’s expense. This is generally not the case for prescriptions of other HIV drugs, which do not receive such high scrutiny from Medicaid and ADAPs. As a result, doctors have experienced a long wait before their patients get financing through these programs, which may contribute to the slow sales of Fuzeon.

“I’m not surprised that they didn’t sell much. No one can get it,” said Dr. Robert Murphy of Northwestern University. While waiting for Fuzeon, Murphy’s patients are staying on failing drug regimens—combinations that do not fully suppress HIV due to drug resistance. “The problem is, the financing is really complicated,” he added.

Further confounding the financing for Fuzeon is the cost of other HIV medications. In the TORO trials, participants were taking as many as four other drugs. The combined cost for such a drug combination could be as high as $40,000. Arranging reimbursement from cash-strapped government agencies for such an expensive combination therapy could cause additional delays.

Holdups in Fuzeon reimbursement have even slowed down enrollment into clinical trials of other experimental drugs. Since Fuzeon is most effective in combination with other active drugs, doctors look for new treatments they can combine with the entry inhibitor. This approach is especially appealing for people with resistance to all other available drugs. Tipranavir, Boehringer Ingelheim’s experimental protease inhibitor, is potentially active against drug-resistant HIV, making it an attractive option for use with Fuzeon in salvage therapy. But for Dr. Joel Gallant, director of the Moore HIV Clinic at Johns Hopkins Hospital, delayed access to Fuzeon is preventing some of his patients from entering a phase III trial with tipranavir. “I have been having an incredibly difficult time getting patients the drug,” said Gallant.

Injection Complications

Despite the advantages of combining Fuzeon with new drugs like tipranavir, not everyone is waiting until new treatments are available. Fuzeon can have a lasting benefit even for people who use it without other active drugs. For Matt Sharp, director of Treatment Education at the Test Positive Aware Network (TPAN) in Chicago, taking Fuzeon for a year and a half has meant going back to work after disability. But the decision to try the drug really depends on how aggressive you are with your treatment, according to Sharp.

“I’m able to come back to work, and my energy is boundless,” said Sharp, whose CD4 count has been gradually increasing since he began taking Fuzeon in a clinical trial. “But I certainly understand why people wouldn’t want to go on a twice-daily injectable drug. It’s an individual choice. It just depends on how tolerant you are,” he added.

Fuzeon causes painful injection site reactions, which seem to persist throughout therapy. One worry is that over time, suitable sites on the body for injecting Fuzeon will become limited due to the longevity of the reactions. Sharp is still battling these nasty reactions, though the injections have become a part of his daily routine.

Others are more reluctant to use Fuzeon. Both Gallant and Murphy have had patients who avoid taking the drug, choosing to stay on failing drug regimens.

Roche acknowledges that injections are a barrier to Fuzeon’s adoption. Van Ness also admits that the complicated process of reimbursement originally caused problems in the distribution of Fuzeon. These delays continue to shape many doctors’ perceptions of the obstacles to Fuzeon access, despite efforts by Roche to accelerate reimbursement. Now, according to Van Ness, it should take approximately two weeks from the time a prescription is received to ship the drug. Some delay is inevitable; along with verifying payment, Roche also has to guarantee at least a six-month supply of the drug for all patients.

Roche and Trimeris announced in Paris that more Fuzeon would be available this year. Initially, they predicted that the complex manufacturing process would hinder its availability, providing enough for only 12,000 to 15,000 people worldwide in 2003. In July, Roche announced that Fuzeon would now be available for at least 18,000 people this year—10,000 to 12,000 in the US. “Our supply is greater than we anticipated, but it is still limited,” said Van Ness.

Whether demand for Fuzeon will catch up to this increased supply is anyone’s guess. Fuzeon is not a simple drug to take, but it may be a long time until an entry inhibitor comes in an easy-to-swallow pill. For now, “it’s too early to make any forecasts,” said Van Ness, referring to future Fuzeon sales. “I don’t think it’s something to worry about yet.”

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