FDA Approvals: Remicade, Gammagard Liquid 10%, Doxorubicin Transdrug

Yael Waknine

May 19, 2005

May 19, 2005 — The U.S. Food and Drug Administration (FDA) has approved infliximab injection to reduce the signs and symptoms of active psoriatic arthritis, a 10% solution of immune globulin G (IgG) intravenous for the treatment of primary immunodeficiency disorders associated with defects in humoral immunity, and an orphan drug formulation of doxorubicin for the treatment of hepatocellular carcinoma.

Infliximab (Remicade) for Treating Psoriatic Arthritis

On May 17, the FDA approved a new indication for infliximab injection (Remicade, made by Centocor, Inc.), allowing its use to reduce the signs and symptoms of active psoriatic arthritis, defined as affecting at least five joints.

The approval was based on the results of the randomized, placebo-controlled, phase 3 Induction and Maintenance of Psoriatic Arthritis Clinical Trial 2 (IMPACT-2) study, showing that infliximab significantly improved symptoms of arthritis and cleared psoriatic lesions in patients with active psoriatic arthritis who had demonstrated inadequate response to disease-modifying antirheumatic drugs (DMARDs).

Infliximab yielded improvements beginning as early as two weeks following therapy initiation and continuing through week 24, as evaluated using the American College of Rheumatology (ACR) scoring criteria and the Psoriasis Area Severity Index (PASI).

At week 14, 58% of patients treated with infliximab demonstrated a 20% or more improvement in arthritis symptoms (ACR 20 scores) from baseline compared with 11% in the placebo group ( P < .001). At 24 weeks, a 70% improvement was observed in 27% of patients treated with infliximab compared with 2% of placebo-treated patients ( P < .001).

Results at week 24 also showed that 60% of patients receiving infliximab experienced at least a 75% improvement in psoriasis symptoms (PASI 75) from baseline compared with 1% of those receiving placebo. In addition, a 90% improvement (PASI 90) was achieved by 39% of infliximab-treated patients and none in the placebo group.

Infliximab therapy was also effective in decreasing symptoms of dactylitis and enthesopathy. Dactylitis was present at baseline in 40% and 41% of patients in the infliximab and placebo groups, respectively. At 24 weeks, only 15% of patients in the infliximab group continued to have symptoms compared with 33% of those administered placebo ( P <= .05).

Enthesopathy, observed at baseline in 42% of patients in the infliximab group and 35% of those in the placebo group, was present at 24 weeks in 22% and 36% of patients in these groups, respectively ( P = .004).

Infliximab was approved in September 2004 by the European Commission for use in combination with methotrexate to treat active and progressive psoriatic arthritis in patients who have had an inadequate response to DMARDS. Infliximab was previously approved by the FDA for the treatment of Crohn's disease, rheumatoid arthritis, and ankylosing spondylitis.

10% IGIV Solution (Gammagard Liquid 10%) for Primary Immunodeficiency Disorders With Humoral Immunity Defects

On April 27, the FDA approved an immune globulin G (IgG) intravenous [human] 10% solution (IGIV; Gammagard Liquid 10%, made by Baxter Healthcare Corp.) for the treatment of primary immunodeficiency disorders associated with defects in humoral immunity.

The approval was based on the results of a phase 3, multicenter study, showing that no validated acute serious bacterial infections occurred in 61 patients treated with 300- to 600-mg per day of the solution every 21 to 28 days for a year.

The ready-to-use, sterile preparation eliminates the need for reconstitution, and its increased concentration compared with previously approved formulations (10% vs 5%) reduces the time required for infusion.

The 10% liquid formulation will be available in 1-, 2.5-, 5-, 10- and 20-g vials for tailored dosing and reduction of waste. It can be stored for nine months at room temperature and for up to 26 months in refrigeration.

Orphan Drug Formulation of Doxorubicin (Transdrug) for Hepatocellular Carcinoma

On April 25, the FDA approved orphan drug status for a new formulation of doxorubicin (doxorubicin Transdrug, made by BioAlliance Pharma), allowing its use for the treatment of hepatocellular carcinoma (HCC).

According to a company news release, the formulation is composed of doxorubicin-laden nanoparticles made using proprietary poly-iso-hexyl-cyanoacrylate polymer technology. The drug particles are able to translocate into cancer cells to exert their cytotoxic effects'.'

The targeted delivery system is designed to bypass multidrug resistance mechanisms and is capable of restoring cancer cell sensitivity to drugs, thereby overcoming the resistance that is often associated with hepatocellular tumors.

Phase 1/2 clinical trials of the orphan drug are currently being completed at eight major centers in France to demonstrate its preferential distribution in the liver and evaluate its efficacy in circumventing cancer resistance.

Orphan drug designation is granted by the FDA to encourage the development of therapies for diseases with a prevalence of less than 200,000 in the U.S. According to the news release, 15,000 cases of HCC are diagnosed each year in the U.S. The survival rate is less than 5% without treatment, and currently there are no approved drug therapies. The only proven potentially curative options for HCC are surgical resection or liver transplantation.

A similar status for the product was granted in the European Union by the Committee for Orphan Medicinal Products of the European Medicines Agency late last year.

Reviewed by Gary D. Vogin, MD

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