FDA Approvals: Arranon, Kaletra Tablets, Soltamox

Yael Waknine

November 03, 2005

Nov. 3, 2005 — The U.S. Food and Drug Administration (FDA) has approved nelarabine intravenous injection for the treatment of T-cell acute lymphoblastic leukemia and lymphoblastic lymphoma in patients who have not responded to or have relapsed after treatment with at least two chemotherapy regimens; a 200-mg/50-mg tablet formulation of lopinavir/ritonavir to replace the currently marketed 133.3-mg/33.3-mg capsules; and an oral solution of tamoxifen citrate for breast cancer indications.

Nelarabine Intravenous Injection (Arranon) for ALL, Lymphoma

On Oct. 28, the FDA granted accelerated approval for nelarabine intravenous injection (Arranon, made by GlaxoSmithKline) for the treatment of T-cell acute lymphoblastic leukemia (T-ALL) and T-cell lymphoblastic lymphoma (T-LBL) in patients who have not responded to or have relapsed after treatment with at least two chemotherapy regimens.

Nelarabine is a prodrug of arabinosylguanine with T-cell selectivity. The nucleoside analog is converted into arabinosylguanine nucleotide triphosphate, which inhibits DNA synthesis and induces apoptosis.

The approval was based on complete response rates induced by nelarabine therapy; randomized trials demonstrating increased survival or other clinical benefits have not been conducted.

Data from a pivotal multicenter, phase 2 clinical study of single-agent therapy with nelarabine in relapsed/refractory patients (28 adults, 39 children) showed that 21% of adults and 23% of children achieved a complete response or complete response without full hematologic recovery.

Remissions were generally of sufficient length to enable stem-cell procedures; median overall survival after nelarabine therapy was 21 weeks in adults and 13 weeks in children.

Hematologic toxicity was the most common moderate to severe (grade 3-4) nelarabine-associated adverse event. As with other cytotoxic agents, nelarabine is associated with treatment-limiting neurologic adverse events; close monitoring of patients is recommended and dosing should be discontinued if neurologic events of grade 2 or greater severity occur.

As a condition of the approval, the company will pursue postmarketing evaluation of the drug's clinical benefit through a randomized, multicenter, phase 3 trial conducted by the Children's Oncology Group under National Institutes of Health sponsorship. The trial will assess event-free survival at four years and minimal residual disease in the postconsolidation phase for patients receiving standard therapy with or without nelarabine.

Nelarabine was previously granted orphan drug status for these indications by the FDA in August 2004 and by the European Commission in June 2005 for the treatment of T-ALL.

Lopinavir/Ritonavir 200-mg/50-mg Tablets (Kaletra) to Replace Capsules for HIV by March 2006

On Oct. 28, the FDA approved a new yellow tablet formulation of 200 mg/50 mg of lopinavir/ritonavir (Kaletra, made by Abbott Laboratories, Inc.) that will replace the currently used 133.3-mg/33.3-mg orange capsules by March 2006.

According to a company news release, the tablets will be available at pharmacies in the next few weeks.

Unlike the capsules, the film-coated tablets can be taken with or without food and do not require refrigeration before or after dispensing. Moreover, fewer tablets than capsules are required per 800-mg/200-mg dose per day (four tablets vs six capsules).

The approval was based on data from pharmacokinetic studies in 141 healthy individuals, showing that four 200-mg/50-mg tablets were bioequivalent to six 133.3-mg/33.3-mg lopinavir/ritonavir capsules.

Lopinavir/ritonavir tablets, capsules, and oral solution are indicated for use in combination with other antiretroviral agents for the treatment of HIV infection.

Tamoxifen Citrate Oral Solution (Soltamox) for the Treatment of Breast Cancer

On Oct. 29, the FDA approved a new 10-mg/5-mL oral solution formulation of tamoxifen citrate (Soltamox, made by Savient Pharmaceuticals, Inc.) for the treatment of breast cancer in adjuvant and metastatic settings; to reduce the risk of breast cancer in women with ductal carcinoma in situ; and to reduce breast cancer incidence in women at high risk of the disease.

The approval was based on data from pharmacokinetic studies showing bioequivalence between similar doses of tamoxifen tablets and solution. Tamoxifen tablets (Nolvadex, made by AstraZeneca) are available in 10- and 20-mg dose strengths.

Tamoxifen oral solution was previously approved for use in the U.K., Ireland, and Germany.

Reviewed by Gary D. Vogin, MD


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