January's approval by the Food and Drug Administration (FDA) of Amevive, the first biologic treatment for chronic plaque psoriasis, is a qualified blessing for the estimated 1.5 million Americans who suffer from the moderate to severe form of the disease. The drug, developed by the Boston-based biotech firm Biogen, Inc., offers hope to those whose disease has passed beyond uncomfortable and inconvenient to debilitating and depressing.
But those people are faced with a distressing trade-off: While Amevive's efficacy in taming psoriasis is well documented, the drug's long-term safety remains largely unknown. Biogen is banking on lots of patients' being willing to accept that risk -- and to pay an extraordinary price: The drug costs $8,000 to $24,000 per year, with the question of insurance coverage unsettled.
Psoriasis is a disease of the immune system in which an errant immune response spurs skin cells multiply too quickly, accumulating on the skin's surface to form raised, scaly patches. In severe cases, the skin not only itches incessantly but cracks and bleeds; one hears of people waking up stuck to their bedsheets or having to vacuum their homes frequently to remove the piles of scaly skin they've shed. The condition can lead to social inhibition and chronic psychological distress. Heartbreak, indeed.
Until Amevive, topical treatment options have included creams, cortisone ointments and phototherapy using UV light. The most commonly used systemic drugs, cyclosporine and methotrexate, which slow the disease by suppressing the entire immune system, remain therapeutic mainstays. Many psoriasis patients (nationwide there are an estimated 4.5 million, suffering different levels of severity) find relief in one or another of these options.
But none has proven useful to all psoriasis sufferers. And few are without significant downsides: Topical treatments sometimes don't offer enough relief. Phototherapy can lead to skin cancer. The systemic drugs are associated with kidney and liver damage and other worrisome side effects.
Amevive has been shown in randomized, placebo-controlled clinical trials to reduce the area of psoriasis-affected skin by 50 percent or more after a single course of treatment in 60 percent of patients, according to Akshay Vaishnaw, Biogen's senior director of medical research. The incidence of short-term side effects in those pre-approval trials was also quite low.
Administered either intravenously or by intramuscular injection over 12 weeks, the drug also shows impressive staying power. While its benefits take weeks to kick in, their median duration is seven months, those studies show. That duration is a key to Amevive's approach: Long holidays from treatment are a real boon to patients, both practically and financially.
As the first psoriasis drug engineered from proteins produced by living cells, Amevive represents a new approach to treating the disease. Unlike drugs that affect the entire immune system, Amevive targets the memory-effector T-cells that trigger the overproduction of skin cells. (Other biologics are in the pipeline: Genentech has filed for FDA approval for its Raptiva, and Amgen's Enbrel, approved last year to treat psoriatic arthritis is in Phase III testing for treating psoriasis itself.)
While that targeted immunosuppressive mechanism is the source of Amevive's promise, it also casts a pall. Interfering with T-cells may increase a person's susceptibility to infection. Moreover, the medication has the potential to cause cancer, a risk that didn't clearly assert itself in clinical trials but that some say has not yet been sufficiently explored.
Biogen is well aware of those risks, but the company reports that the rate of infections among patients receiving Amevive during clinical trials was nearly identical to the rate among patients receiving placebo. Still, all patients receiving the medication will receive regular blood tests so any dips in white-blood-cell counts resulting from immune-system suppression can be caught early and restored to normal through discontinuation of Amevive. As for the cancer risk, Vaishnaw notes that most of the malignancies among clinical trial participants were squamous- and basal-cell skin cancers of the type commonly seen in psoriasis patients who have previously received cyclosporine or phototherapy treatments.
The FDA, persuaded by the drug's efficacy data and lack of short-term side effects, determined that the benefits exceeded the potential risks. But the terms of the FDA's approval require Biogen to conduct further studies, including one that will track 5,000 patients for infections and malignancies for five years.
In essence, then, those who sign on early will be participants in Biogen's ongoing clinical research.
Fine by us, says the Psoriasis Foundation of America, a nonprofit advocacy group that receives major funding from Biogen and other drug manufacturers.
"We have heard from numerous patients suffering moderate to severe psoriasis that they are willing to accept risks to have relief from the physical and emotional manifestations of the disease," says Molly Marshall, a spokeswoman for the foundation.
The group, which last year spoke before the FDA in favor of Amevive's approval, says its research shows that a third of those with moderate to severe psoriasis are "very unsatisfied" with available treatments and that 78 percent are not using existing therapies because of their toxicity and lack of efficacy.
Noting the known risks of liver and kidney damage and skin cancer that are associated with other treatments, Marshall says, "a lot of moderate-to-severe patients have said they don't want those specific safety issues." Though she acknowledges that "it's kind of weird," she says that some of the foundation's constituents may be more willing to accept the less-defined risks of the new drug than to embrace older drugs' better-known hazards.
Steve Wiseman, founder of the Maryland-based International Psoriasis Community, a support and advocacy group, isn't ready to try Amevive yet. Wiseman, who has had psoriasis for 14 years, says, "I personally am somewhat concerned about taking such a biologic. Even though I've heard people have great responses to it, I've decided not to jump on this bandwagon right away," if only because Amevive is so new.
Those who do make the leap will need to deal with the cost: A 12-week course of Amevive costs between about $8,000 (for the intravenous version) and close to $12,000 (for the intramuscular administration). Because many patients will require a second course (after a requisite 12-week break), even those whose benefits last seven months may find themselves shelling out twice those amounts in a calendar year.
While Biogen and insurance companies have yet to work out questions about reimbursement, some experts are concerned that insurers may be reluctant to pay such prices when existing treatments are so much less expensive. (Methotrexate, for example, costs about $1.50 per pill, with patients taking six to 10 pills weekly.)
Mervyn Elgart, emeritus professor and former chairman of dermatology at George Washington University School of Medicine, says he thinks Amevive is "a good medication [but] expensive as hell." Elgart says he's inclined to continue to use "one of the more frequently used drugs, like methotrexate," until Amevive's safety profile becomes better defined.
"You really find out about a drug when it becomes public, when there have been a couple million doses," Elgart says. "We need to find out how much of a problem this really is."
Jennifer L. Huget is a frequent contributor to The Post.