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Federal Advisory Committee Recommends Approval of New Psoriasis Drug

In a unanimous vote on Sept. 9, an advisory committee to the U.S. Food and Drug Administration (FDA) recommended approval of the psoriasis drug efalizumab (brand name Raptiva) for the treatment of moderate to severe stable plaque psoriasis. The Dermatologic and Ophthalmic Drug Advisory Committee (DODAC) will report its recommendation to the FDA, which has final say in all drug approvals. Genentech, the drug's manufacturer, expects approval by the end of October.

A majority of committee members said they were impressed with the effectiveness of Raptiva in clinical studies. For example, researchers had presented findings that 44 percent of patients treated continuously with Raptiva for 24 weeks saw the severity of their psoriasis improve by 75 percent or more. A longer study monitored patients for 21 months who had improved significantly and continued to take Raptiva weekly. Of those patients, 67 percent of patients achieved a 75 percent improvement in psoriasis severity.

Raptiva is given by injection under the skin; patients give themselves a shot once per week at home.

However, the committee also expressed anxiety over the lack of evidence on the drug's long-term safety. Several DODAC members suggested that Genentech conduct more studies to evaluate the side effects of the drug after it is approved. In Raptiva's clinical studies, serious side effects were rare, but included psoriasis relapse, arthritis and thrombocytopenia (low platelet counts).

In order to judge accurately the significance of the side effects, panel members recommended that physicians monitor their patients. Andrew Blauvelt, M.D., a consultant to the committee and a member of the Psoriasis Foundation's Medical Board, suggested that in order to monitor for low platelet counts, doctors test once per month for the initial three-month treatment period, and then fewer tests after.

The panel also recommended that Genentech conduct research to identify patients who may be at higher risk of relapse, defined as loss of 50 percent or greater of the psoriasis severity improvement obtained during the first treatment period. In clinical trials involving 2,500 patients treated with Raptiva, 19 were hospitalized for psoriasis flares, including plaque psoriasis that turned into erythrodermic, guttate or pustular types of the disease, after they stopped taking the medication.

Initial approval should include only the adult psoriasis population, according to the committee. Genentech is pursuing studies for psoriatic arthritis and may pursue studies for Raptiva's use in children. The company will research which drugs may be used with Raptiva or after stopping treatment.

Raptiva may join growing biologic class
Raptiva is an antibody that blocks the activation of certain immune cells, called "T cells," and the migration of those cells into the skin. T cells are a type of white blood cell in the body that normally help us ward off foreign invaders and fight infection. In psoriasis, however, these T cells are mistakenly activated and trigger other immune responses that fuel the development of psoriasis lesions.

The most common side effects reported from the phase III trials were headache, infection (such as common colds), chills, nausea and pain (unrelated to injection), with most reactions occurring after the first one or two injections during the initial 12-week treatment. By the third injection, side effects were similar to those on placebo. No new side effects were observed during long-term Raptiva therapy. The number of side effects decreased over time from 57 percent during months 4 to 6 to nearly 50 percent from months 16 to 18.

In January 2003, Amevive (pronounced AM-uh-veev), manufactured by Biogen, became the first biologic medication to be approved for treating psoriasis. Enbrel, manufactured by Amgen and co-marketed by Wyeth, was approved for psoriatic arthritis in January 2002. These and other medications are part of this new class of biologic medications, which interfere with very specific parts of the immune responses involved in psoriasis, psoriatic arthritis and other immune-related diseases.

Psoriasis Foundation plays key role
The National Psoriasis Foundation played a significant role in the approval by testifying to the need for new psoriasis treatments. Leslie Holsinger, Ph.D., chairman of the Psoriasis Foundation Board of Trustees, shared her experience with psoriasis during the public testimony portion of the hearing.

"It is incredibly challenging to find good treatments," Holsinger said. "They may stop working, and the side effects may be difficult to tolerate."

"Also, most treatments are not compatible with pregnancy. Raptiva may offer more options for women and men where options are sorely lacking," said Holsinger, a psoriasis patient for more than 15 years. Raptiva "washes out" of the body soon after stopping treatment. "By sharing my story, I hope the FDA will better understand the urgency felt in the psoriasis community for more treatment options."

Her testimony was followed by Mark Lemelin, a Psoriasis Foundation member from Broomfield, Colo., who has coped with psoriasis for over 25 years. "When I was diagnosed, I made the decision that it wouldn't affect my lifestyle. It was important to not think of myself as a victim."

But the reality of living with his psoriasis made it difficult to cope, and his treatments eventually stopped working. "There is not a single waking moment that my sensory system is not overloaded because of my psoriasis," Lemelin said. "Because of it, I'm not always able to function. But Raptiva totally cleared my psoriasis. Compared with every treatment I've tried, nothing is easier to administer."

Robin Pevnick, another member of the Psoriasis Foundation, testified to the effectiveness of the drug. Her use of topicals, over-the-counter products, PUVA, home UVB, methotrexate and cyclosporine gradually failed, and she eventually gave up on finding effective treatments. "I stopped going to doctors because I felt like nothing was working," she explained. At a friend's urging, she joined a Raptiva trial, and she noticed rapid improvement after two weeks. "I was completely clear for the first time in 20 years."

"There is a terrific need for therapies that make sense," Pevnick said.

Since it was founded in 1968, the Psoriasis Foundation has testified before the FDA multiple times to support the approval of new therapies for psoriasis. As an organization, the Psoriasis Foundation does not recommend or endorse any particular treatment or product. However, we do advocate to ensure that people with psoriasis and psoriatic arthritis have access to as many potentially safe and effective treatment options as possible. This is part of our mission of improving the quality of life of people who have these diseases.

The FDA review process
After the public testimony, the committee discussed the drug, followed by an FDA presentation reviewing the clinical trial results. The FDA is the federal agency charged with protecting public health by reviewing and monitoring a wide variety of products-from common food ingredients to complex surgical devices to cutting-edge medical treatments.

According to the FDA Web site:

• The FDA may seek a committee's opinion about a new drug, a major new indication for an already approved drug, or a special regulatory requirement being considered, such as a boxed warning in a drug's labeling.
• The committees may advise FDA on necessary labeling information, and help with guidelines for developing particular kinds of drugs, such as those for anesthesia, heartbeat irregularities, and cancer.
• They also may address such questions as whether a proposed study for an experimental drug should be conducted and whether the safety and effectiveness information submitted for a new drug is adequate for marketing approval.

Resources

The following links take you off the National Psoriasis Foundation Web site. We are not responsible for the content of any linked site.

The agenda, list of participants and briefing statement is available at the FDA Web site, under Dermatologic and Ophthalmic Drugs Advisory Committee.

Genentech broadcasted a free audio Webcast after the FDA hearing at www.gene.com. It will be available for viewing until 5:00 p.m. Pacific time, Sept. 16.