FDA Approvals: Remicade, Neulasta, NovoLog

Yael Waknine

September 22, 2005

Sept. 22, 2005 — The U.S. Food and Drug Administration (FDA) has approved infliximab injection for the treatment of ulcerative colitis; pegfilgrastim injection for use in the first cycle of chemotherapy associated with a 17% or higher risk of neutropenia; and insulin aspart [rDNA origin] injection for the treatment of pediatric diabetes types 1 and 2.

Infliximab (Remicade) for the Treatment of Ulcerative Colitis

On Sept. 15, the FDA approved a new indication for infliximab injection (Remicade, made by Centocor, Inc.), allowing its use in reducing signs and symptoms, achieving clinical remission and mucosal healing, and eliminating corticosteroid use in patients with active moderate to severe ulcerative colitis (UC) who have had an inadequate response to conventional therapy.

The approval was based on data from two randomized phase 3 clinical trials in 728 patients. The first study, ACT 1, involved patients refractory to treatment with corticosteroids and/or 6-mercaptopurine/azathioprine; the second study, ACT 2, involved patients refractory to at least one standard therapy of immunosuppressants, corticosteroids, or 5-aminosalicylic acid. Both trials yielded similar results.

In ACT 1, treatment with 5 and 10 mg/kg of infliximab induced a significantly higher rate of clinical response at week 8 compared with placebo (69% and 62% vs 37%; P < .001 for both). Clinical response was maintained at week 30 in 52% and 51% of infliximab-treated patients, respectively, compared with 30% of those receiving placebo (P < .001 and P < .01).

The rate of clinical remission at week 8 was also significantly increased in patients receiving 5 and 10 mg/kg of infliximab (39% and 32% vs placebo, 15%; P < .001 and P < .01) and was also maintained at week 30 (34% and 37% vs placebo, 16%; P < .001 for both).

Infliximab-treated patients were also significantly more likely to achieve mucosal healing at week 8 compared with placebo (62% and 59% vs 34%), an improvement that persisted at week 30 (50% and 49% vs 25%; P < .001 for all).

Moreover, a significantly greater proportion of patients treated with infliximab were able to discontinue corticosteroid therapy while in remission at week 30 compared with placebo (24% and 19% vs 10%; P = .030 and .125, respectively).

In ACT 2, 65% and 69% of patients treated with 5 and 10 mg/kg of infliximab experienced a clinical response at week 8 compared 29% of those receiving placebo (P < .001 for both), and the response was maintained at week 30 in 47% and 60% of patients, respectively, compared with 26% for those receiving placebo (P < .001 for both).

At week 8, a significantly increased proportion of patients treated with 5 and 10 mg/kg of infliximab were in clinical remission (34% and 28% vs placebo, 6%; P < .001 for both), and the improved remission rates persisted at week 30 (26% and 36% vs placebo, 11%; P < .01 and P < .001).

Mucosal healing rates at week 8 were also significantly higher in patients treated with infliximab compared with placebo (60% and 62% vs 31%) and persisted at week 30 (46% and 57% vs 30%; P < .001 for all).

The corticosteroid discontinuation rate at week 30 was significantly higher in infliximab-treated patients compared with placebo (18% and 27% vs 3%; P = .010 and P < .001, respectively).

Adverse events reported in these trials were similar to those observed in trials for previously approved indications, including rheumatoid arthritis, Crohn's disease, ankylosing spondylitis, and psoriatic arthritis.

Pegfilgrastim (Neulasta) Indication Expanded to Include Lower-Risk Chemotherapy

On Sept. 15, the FDA approved an expanded indication for pegfilgrastim injection (Neulasta, made by Amgen, Inc.), allowing its use in the first cycle of a chemotherapy regimen associated with a 17% or higher risk of neutropenia and subsequent cycles thereafter.

Pegfilgrastim was previously approved for first and subsequent cycle administration in patients undergoing myelosuppressive chemotherapy associated with a more than 30% to 40% risk of febrile neutropenia.

The approval was based on data from a randomized phase 3 clinical trial in 928 patients. The study results showed that initiation of pegfilgrastim therapy with the first chemotherapy cycle decreased the incidence of febrile neutropenia by 94% (1% incidence vs placebo, 17%); the incidence of hospitalization by 93% (1% incidence vs placebo, 14%); and use of intravenous anti-infective by 80% (2% incidence vs placebo, 10%) in patients receiving moderately myelosuppressive chemotherapy.

Insulin Aspart (NovoLog) for Use in Children and Adolescents

On Sept. 13, the FDA approved an expanded indication for insulin aspart [rDNA origin] injection (NovoLog, made by Novo Nordisk, Inc.), allowing its use for the treatment of diabetes types 1 and 2 in children. The rapid-acting insulin formulation was previously approved for use only in adults.

The approval was based in part on data from a 24-week, parallel-group study of 283 children and adolescents aged six to 18 years with type 1 diabetes. The study showed that insulin aspart achieved a level of glycemic control (as measured by hemoglobin A1C) comparable to that of the company's regular human insulin (Novolin R).

A similar study in 26 children aged two to six years with type 1 diabetes showed that insulin aspart and regular human insulin yielded similar levels of A1C and fructosamine glycemic control.

Rates of hypoglycemia were similar between treatment groups in both studies.

Reviewed by Gary D. Vogin, MD

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