FDA Approvals: Tysabri, Nexium, CR002, Sotradecol

Yael Waknine

December 02, 2004

Dec. 2, 2004 — The U.S. Food and Drug Administration (FDA) has approved natalizumab to reduce the frequency of relapse in patients with multiple sclerosis; esomeprazole to reduce the risk of gastric ulcer associated with continuous nonsteroidal anti-inflammatory drug use; orphan drug status for CR002 to reduce the progression of IgA nephropathy and delay kidney failure; and sodium tetradecyl sulfate injection for varicose veins.

Natalizumab (Tysabri) for the Reduction of Relapse Frequency in Multiple Sclerosis

On Nov. 23, the FDA licensed the recombinant humanized IgG4k monoclonal antibody natalizumab (Tysabri; previously known as Antegren, made by Biogen Idec, Inc.) for use in reducing the frequency of clinical exacerbations in patients with relapsing forms of multiple sclerosis (MS).

Natalizumab contains human framework regions and the complementarity-determining regions of a murine antibody that binds to α4-integrin. It is the first α4 antagonist in the new selective adhesion molecule inhibitor class, and it is designed to selectively inhibit immune cell migration from the bloodstream into chronically inflamed tissue.

The approval was based on 13-month interim results of two ongoing two-year, randomized, multicenter, double-blind, placebo-controlled, phase 3 studies involving more than 2,100 patients with MS. Data from the first study showed that natalizumab significantly reduced the incidence of relapse (66% reduction; annualized relapse rate, 0.25 vs 0.74; P < .001) compared with placebo.

Data from the second study showed that the addition of natalizumab to interferon ß-1a therapy significantly reduced the incidence of relapse (54% reduction; annualized relapse rate, 0.36 vs 0.78; P < .001) compared with interferon ß-1a alone.

Serious adverse reactions were rare and included infection (including pneumonia), temporary hypersensitivity reactions, depression, and cholelithiasis. Common adverse events were generally mild and included nonserious infections, headache, depression, arthralgia, and menstrual disorders.

Natalizumab is administered in a 300-mg dose by intravenous infusion every four weeks. It is supplied as a concentrate of 300 mg/15 mL that is diluted into 100 mL of normal saline and infused over one hour.

Esomeprazole (Nexium) for the Reduction of Gastric Ulcers Linked With NSAID Use

On Nov. 29, the FDA approved a new indication for esomeprazole (Nexium, made by AstraZeneca plc), allowing its use in the reduction of gastric ulcer development in at-risk patients receiving continuous nonsteroidal anti-inflammatory drug (NSAID) therapy.

The approval was based on the results of two multicenter, placebo-controlled, double-blind clinical studies involving 1,429 patients with a chronic condition requiring daily NSAID therapy. At six months, 95.4% to 96.7% of patients treated with esomeprazole in the first study and 94.7% to 95.3% in the second study remained free of gastric ulcers.

Esomeprazole was previously approved by the FDA for the treatment of gastroesophageal reflux disease, the healing of erosive esophagitis and the maintenance of symptom resolution, and as part of a regimen in eradicating Helicobacter pylori infection. An indication allowing its use in the healing of gastric ulcers is currently under FDA review.

Indications for the healing of gastric ulcers and the prevention of gastric and duodenal ulcers associated with NSAID therapy were approved in the European Union in September.

Orphan Drug Status for CR002; May Slow Progression of IgA Nephropathy

On Nov. 11, the FDA approved an orphan drug designation for a fully human monoclonal antibody (CR002, made by CuraGen Corporation), as a potential treatment to slow or prevent kidney failure in patients with IgA nephropathy.

CR002 neutralizes platelet-derived growth factor D, a mediator that stimulates mesangial cell proliferation and is implicated in the pathogenesis of the disease. Animal studies of glomerular nephritis suggest that neutralization of the growth factor by CR002 can significantly reduce tissue scarring in the kidney and may preserve its function.

A phase 1 trial will be conducted to evaluate the safety, tolerability, and pharmacokinetics of CR002 in humans.

Sodium Tetradecyl Sulfate Injection (Sotradecol) for Varicose Veins

On Nov. 12, the FDA approved sodium tetradecyl sulfate injection (Sotradecol, made by Bioniche Life Sciences) for the treatment of small, uncomplicated varicose veins of the lower extremities that show simple dilation with competent valves. The injection is commonly used in sclerotherapy.

The abbreviated new drug application was granted expedited review due to a nationwide shortage of the product. The company anticipates availability of the 1% and 3% strengths in mid-December.

Sodium tetradecyl sulfate was originally approved in 1946. Product manufacture was discontinued by Elkins Sinn in 2000 for reasons other than safety or effectiveness.

Reviewed by Gary D. Vogin, MD

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