International Approvals: Singulair and Gardasil/Silgard

Yael Waknine

October 02, 2006

October 2, 2006 ---- Health Canada has approved a new indication for montelukast sodium, allowing its use for the relief of symptoms associated with seasonal allergic rhinitis in patients aged 15 years and older; the European Commission has approved a quadrivalent recombinant vaccine for the prophylaxis of diseases caused by human papillomavirus types 6, 11, 16, and 18 in women aged 9 to 26 years.

Montelukast (Singulair) for Symptomatic Relief of Perennial Allergic Rhinitis in Canada

On September 19, Health Canada approved a new indication for montelukast sodium ( Singulair tablets and chewable tablets, made by Merck Frosst Canada Ltd), allowing its use for the relief of symptoms associated with seasonal allergic rhinitis in patients aged 15 years and older.

According to a company news release, the condition affects 20% to 25% of Canadians and up to 75% of asthma patients. If poorly managed, allergic rhinitis can increase the risk for an asthma attack and asthma-related hospitalization. Because the 2 conditions are often comorbid, patients with asthma should always be evaluated for allergic rhinitis as a trigger for their asthma and patients with allergic rhinitis should be evaluated for asthma.

Approval of the allergic rhinitis indication for montelukast sodium was based on data from two 6-week, randomized, placebo-controlled, double-blind studies in 3357 patients aged 15 to 82 years.

Results of the first trial showed that once-daily treatment with 10 mg of montelukast sodium significantly decreased daytime symptoms of nasal congestion, rhinorrhea, and sneezing from baseline during a 6-week period compared with placebo (composite score, -0.42 vs -0.35; difference, -0.08; 95% confidence interval [CI], -0.12 to -0.04; P < .001).

In the second study, nasal itching was added to the primary outcome variable, and results showed the estimated difference between montelukast sodium and placebo to be -0.04 (95% CI, -0.09 to 0.01). The study was not designed for statistical comparison between montelukast sodium and the active control (certirizine 10 mg); the difference between certirizine and placebo was -0.10 (95% CI, -0.19 to -0.01).

Montelukast was generally well-tolerated, with a safety profile similar to that of placebo. Adverse events varied by age; those occurring in at least 1% of montelukast-treated patients at a rate greater than placebo included sinusitis, upper respiratory tract infection, sinus headache, cough, epistaxis, and increased alanine aminotransferase levels.

Montelukast previously was approved by the US Food and Drug Administration in July 2005 to relieve symptoms of perennial allergic rhinitis in patients aged 6 months and older; oral granules (4 mg) are marketed for use in children aged 6 months to 5 years.

The drug was previously approved by the FDA and Health Canada for the prophylaxis and chronic treatment of asthma, including prevention of day and nighttime symptoms in patients aged 2 years and older; the treatment of acetylsalicylic acid--sensitive asthmatic patients; and the prevention of exercise-induced bronchoconstriction in patients aged 15 years and older.

HPV Vaccine (Gardasil/Silgard) for the Prevention of Cervical Cancer and Other Diseases in EU

On September 22, the European Union approved a quadrivalent recombinant vaccine ( Gardasil, made by Merck & Company, Inc) for the prophylaxis of diseases caused by human papillomavirus (HPV) types 6, 11, 16, and 18 in girls and women aged 9 to 26 years. The approval applies to the 25 member countries of the European Union, including France, Germany, Italy, Spain, and the United Kingdom.

The product will be marketed as Gardasil by Sanofi Pasteur MSD (a joint venture between Sanofi Pasteur and Merck & Company) in 19 European countries (including 15 in the EU). In other Central and Eastern European countries, the vaccine will be marketed by Merck Sharp & Dohme as either Gardisil or Silgard.

The vaccination regimen consists of 3 separate 0.5-mL doses given at baseline, 2, and 6 months by intramuscular injection in the deltoid region of the upper arm or higher anterolateral area of the thigh. Its use is intended for the prevention of cervical cancer, high-grade cervical dysplasias/precancers (cervical intraepithelial neoplasia [CIN 2/3]), high-grade/precancerous vulvar dysplastic lesions (VIN 2/3), and external genital warts (condyloma acuminata) caused by HPV types 6, 11, 16 and 18.

According to a company news release, cervical cancer remains the second most common cause of death from cancer (after breast cancer) among young European women aged 15 to 44 years. Approximately 33,500 women are diagnosed with and 15,000 women die from cervical cancer each year in Europe, and hundreds of thousands of women are diagnosed with cervical, vulvar or vaginal precancer. Also, genital warts continue to be a growing problem in the EU.
The approval was based on clinical study data showing that the vaccine was 100% effective for preventing HPV 16- and 18-related cervical precancers and noninvasive cervical cancers compared with placebo.

It also prevented 95% of HPV-related CIN 2/3 and adenocarcinoma in situ cases; 99% of genital warts cases; and 100% of HPV 16- and 18-related vulvar and vaginal precancers (VIN 2/3 or VaIN 2/3) in women not previously exposed to these HPV types.

HPV vaccine was generally well tolerated in clinical studies; adverse events occurring at an increased frequency compared with placebo included pain (83.9% vs 75.4%), swelling (25.4% vs 15.8%), erythema (24.6% vs 18.4%), fever (10.3% vs 8.6%), and pruritus (3.1% vs 2.8%). Most injection-site reactions were reported to be mild to moderate in intensity.

The vaccine was approved by the US Food and Drug Administration and Health Canada in June and July 2006, respectively.


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