New FDA Approvals

The FDA recently approved these drugs:

Remicade (infliximab) was approved to treat children with active Crohn's disease. FDA said Centocor's infliximab is a genetically engineered monoclonal antibody that reduces inflammation by blocking the action of tumor necrosis factor-alpha (TNF-a). It initially was approved in 1998 to treat Crohn's disease in adults.

Infliximab's safety and effectiveness in pediatric Crohn's disease were assessed in a randomized study of 112 children ages 6-17 with moderately to severely active Crohn's disease who had an inadequate response to conventional therapies. The proportion of patients who achieved clinical response compared favorably with the proportion of adults in an earlier infliximab study in adult Crohn's disease, FDA said, and the pediatric trial's results showed no new safety concerns not already expressed in the product's current label.

In general, the agency said, infliximab's safety profile in the pediatric trial was similar to data presented at a March 2003 FDA Arthritis Advisory Committee meeting, dealing with the extent to which anti-TNF therapies may increase the risk of serious infections and malignancies, such as sepsis and pneumonia in certain patients.

More recently, FDA has received what it said are rare post-marketing reports of an aggressive and often fatal type of T-cell lymphoma in adolescent and young adult patients with Crohn's disease. In most, but not all, cases these patients were treated with standard immunosuppressive therapies in combination with infliximab. FDA is working with Centocor to address this risk by updating the label's Warning section.

Zostavax (Zoster Vaccine Live), a new Merck vaccine to reduce the risk of shingles (herpes zoster) was licensed for use in people age 60 and older. FDA said shingles is caused by the varicella-zoster virus, which also causes chickenpox. After a chickenpox attack, the virus lies dormant in certain nerve tissue and, as people age, may reappear in the form of shingles, which is estimated to affect 20% of people in their lifetime.

A live virus vaccine, Zostavax was shown to boost immunity against varicella-zoster virus, which is thought to be the mechanism by which it protects against zoster and its complications. The vaccine is given as a single injection under the skin, preferably in the upper arm.

The vaccine was studied in some 38,000 individuals throughout the United States ages 60 and older. Half received Zostavax and half received a placebo. All study participants were followed for an average of three years to see if they developed shingles and, if they did, how long the pain lasted.

Researchers found that overall, in those ages 60 and older, the vaccine reduced shingles occurrence by about 50%. For individuals ages 60-69, it reduced occurrence by 64%.

The most common side effects in those who tested the vaccine were redness, pain and tenderness, swelling at the injection site, itching, and headache. The percent of significant adverse events observed in the study was not different between persons who received the vaccine vs. placebo.

As part of the development program, a smaller study was conducted to look more closely at safety. In the smaller study, serious adverse events for all age groups were noted more frequently in those who received the vaccine (1.9%) than those who received placebo (1.3%). FDA said that although it has concluded that available data do not establish that the events are related to the vaccine, Merck will perform a postmarketing study to provide additional safety information.

Dacogen (decitabine) injection treatment for myelodysplastic syndromes (MDS). Decitabine is manufactured by Pharmachemie B.V. Haarlem, The Netherlands, for MGI Pharma Inc., Bloomington, MN. It is a new molecular entity that received orphan drug status.

FDA said patients with MDS have bone marrow that does not produce enough mature blood cells, causing a lack of healthy blood cells that can function properly in the body. Decitabine is thought to work by promoting normal development of blood cells.

MDS can develop following treatment with drugs or radiation therapy for other diseases, or it can develop without any known cause. Some forms of MDS can progress to acute myeloid leukemia, a type of cancer in which too many white blood cells are made.

Decitabine's safety and effectiveness were demonstrated in a randomized, controlled trial in which patients received either decitabine or the standard therapy, and in two nonrandomized studies in which all of the patients received Decitabine. It was evaluated in a total of 268 patients, and some 22% of patients in the three trials had complete or partial responses to the drug. Responses consisted of complete or partial normalization of blood counts and of fewer immature cells in the bone marrow. In responders, the need for transfusions was eliminated during the response period.

The most common side effects reported in clinical trials included neutropenia, thrombocytopenia, anemia, fatigue, fever, nausea, cough, bleeding in the skin, constipation, diarrhea, and hyperglycemia.

Azilect (rasagiline), Teva Pharmaceuticals' new molecular entity for treating Parkinson's disease. Rasagiline is a monoamine oxidase type-B inhibitor that blocks the breakdown of dopamine, a chemical that sends information to the parts of the brain that control movement and coordination.

Rasagiline was approved for use as an initial single drug therapy in early Parkinson's disease and as an addition to levodopa in more advanced patients. Levodopa is a standard treatment for Parkinson's disease.

The drug's safety and effectiveness were assessed in three 18- to 26-week studies. One study compared rasagiline's effects with those of placebo in 404 patients with early Parkinson's. Compared with patients on placebo, the condition of patients on rasagiline showed significantly less worsening on a rating scale that measures the ability to perform mental and motor tasks as well as daily living activities.

The other two studies compared rasagiline's effects with placebo when taken together with levodopa by more than 1,100 patients with more advanced Parkinson's. In these studies, patients using rasagiline together with levodopa had significantly less time per day with relatively poor function and mobility as compared with patients on levodopa and placebo.

Rasagiline may be associated with hypertensive crisis if patients also consume tyramine-rich foods, beverages (such as cheese or red wine) or dietary supplements or amines contained in many cough/cold medications. During development, melanoma was diagnosed in a small number of patients treated with rasagiline. Although FDA concluded that available data don't establish that the drug is associated with an increased melanoma risk, the agency said it appears that compared to the general population, patients with Parkinson's disease have an increased risk of this form of skin cancer. To address the question of whether rasagiline itself increases such risk, Teva will perform a Phase 4 postmarketing study. The product labeling will recommend that patients undergo periodic dermatologic examinations.