International Approvals: Actonel, Alvesco, Increlex

Yael Waknine

August 27, 2007

August 27, 2007 -- Health Canada has approved a 75-mg tablet strength of risedronate sodium for use twice monthly in the prevention and treatment of postmenopausal osteoporosis and the use of inhaled ciclesonide for the prophylaxis of asthma in patients aged 12 years and older. The European Commission has approved mecasermin [rDNA origin] 10-mg/mL injection for the long-term treatment of growth failure in children and adolescents with severe primary insulin growth factor 1 deficiency.

Two-Dose Monthly Regimen for Risedronate ( Actonel) for Osteoporosis in Canada

On July 17, Health Canada approved a new 75-mg strength and associated dosing regimen for risedronate sodium tablets ( Actonel, Proctor & Gamble Pharmaceuticals Canada, Inc) that gives patients the option of taking a 75-mg tablet on 2 consecutive days each month for the prevention and treatment of postmenopausal osteoporosis.

The convenience of a monthly 2-day dose may appeal to patients taking a daily 5-mg dose or weekly 35-mg dose, the company says in a news release.

Approval of the 2-day monthly regimen was based on data from an active-controlled double-blind study(n = 1229), which showed that the drug's use yielded similar increases from baseline in mean bone mineral density at the lumbar spine, total hip, and hip trochanter compared with the daily 5-mg dose.

At 1 year, the mean increase from baseline in lumbar spine bone mineral density was 3.6% (95% confidence interval [CI], 3.3 - 3.9) compared with 3.4% (95% CI, 3.1 - 3.7) for those receiving 5 mg/day of risedronate (mean difference between groups, --0.2%; 95% CI, --0.2 to 0.6).

Adverse events were similar between the groups, with constipation (7.6% vs 7.3%), back pain (8.8% vs 10.8%), arthralgia (10.4% vs 9.5%), nausea (7.3% vs 5.9%), diarrhea (6.2% vs 5.9%), headache (6.3% vs 4.6%), and influenza (6.0% vs 5.4%) reported most frequently. To reduce the risk for gastrointestinal disorders, risedronate should be taken while in an upright position with a full glass of water at least 30 minutes before the first food or drink of the day.

The regimen previously was approved by the US Food and Drug Administration on April 16, 2007. Risedronate is also approved in Canada and the United States to increase bone mass in osteoporotic men (one 35-mg tablet weekly), the treatment and prevention of glucocorticoid-induced osteoporosis (one 5-mg tablet daily), and the treatment of Paget's disease (30 mg/day for 2 months).

Ciclesonide ( Alvesco) for Use in Asthmatic Adolescents in Canada

On July 20, Health Canada approved an expanded indication for the inhaled corticosteroid ciclesonide ( Alvesco, Altana Pharma, Inc [recently acquired by Nycomed Canada, Inc]), allowing its use for the prophylactic management of steroid-responsive bronchial asthma in adolescent patients aged 12 years and older. Previously, ciclesonide therapy had been limited to adult use.

The expanded indication previously was approved by the European Commission in February 2006. Inhalational ciclesonide has not been approved by the US Food and Drug Administration.

Mecasermin Injection ( Increlex) for IGF Deficiency in Children and Adolescents in EU

On August 9, the European Commission approved mecasermin [rDNA origin] 10-mg/mL injection ( Increlex, Ipsen, Inc, under license from Tercica, Inc), allowing its use in the European Union for the long-term treatment of growth failure in children and adolescents with severe primary insulin growth factor 1 deficiency (IGFD). Orphan drug status was also granted for the product.

The approval was based on clinical data from 76 patients who received mecasermin therapy for up to 12.5 years, showing that mean height velocity increased from a 2.8 cm/year (1.1 inches/year) at baseline to 8.0 cm/year (3.1 inches) and 5.8 cm/year (2.3 inches) during the first and second year, respectively ( P < .0001). The growth rate then stabilized at about 4.7 cm/year (1.9 inches/year) from the fourth year of treatment onward.

Adverse events reported in more than 10% of patients included hypoglycemia, thymus hypertrophy, headache, hypoacusis, tonsillar hypertrophy, snoring, and injection site hypertrophy.

The recommended starting dose for mecasermin is 40 to 80 µg/kg twice daily by subcutaneous injection, administered within 20 minutes of a meal or snack. If well tolerated for at least 1 week, the dose may be increased by 40 µg/kg/dose to a maximum of 120 µg/kg given twice daily.

Mecasermin injection previously was approved by the US Food and Drug Administration in August 2005 for the IGFD indication and to treat children and adolescents with growth hormone (GH) gene deletion who have developed neutralizing antibodies to GH.


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