International Approvals: Aerius, Sebivo, Rapydan

Yael Waknine

May 07, 2007

May 7, 2007 — The European Commission (EC) has approved desloratadine 2.5- and 5-mg orodispersible tablets and 0.5 mg/mL oral solution for the once-daily treatment of symptoms associated with allergic rhinitis and chronic idiopathic urticaria; and telbivudine 600-mg once-daily tablets for the first-line treatment of chronic hepatitis B in adult patients with evidence of viral replication and liver disease. Sweden’s Medical Products Agency has approved a lidocaine plus tetracaine 70-mg/70-mg local-anesthetic patch to provide topical anesthesia for needle puncture in patients aged 3 years and older and for superficial surgical procedures in adults.

Desloratadine Orodispersible Tablets and Oral Solution (Aerius) in EU

On April 24, Schering-Plough Corporation announced EC approval of desloratadine orodispersible tablets and oral solution, to be marketed in the 27 member states of the European Union (EU) and in Iceland and Norway as Aerius, Azomyr, and Neoclarityn.

The orally disintegrating, tutti-frutti-flavored tablets are indicated for the once-daily treatment of symptoms associated with allergic rhinitis and chronic idiopathic urticaria (CIU) in patients 6 years and older. They are available for use in 2.5- and 5-mg strengths for those aged 6 to 11 years and 12 years and older, respectively. The sugar- and dye-free 0.5 mg/mL oral solution is indicated for the once-daily treatment of allergic rhinitis and CIU symptoms in patients 1 year and older.

Desloratadine orally disintegrating tablets (Clarinex RediTabs) and syrup (Clarinex, Schering Corp) were previously approved by the US Food and Drug Administration (FDA) for the treatment of symptoms associated with seasonal allergic rhinitis in patients 2 years and older, the relief of perennial allergic rhinitis in patients 6 months and older, and the symptomatic relief of pruritus and reduction of hive number and size in patients 6 months and older with CIU.

Telbivudine (Sebivo) for First-Line Treatment of HBV Infection in EU

On April 30, the EC approved telbivudine 600-mg tablets (Sebivo, made by Idenix Pharmaceuticals, Inc [co-promoted with Novartis Pharma AG]) for the first-line, once-daily treatment of chronic hepatitis B virus infection (HBV) in adult patients with compensated liver disease and evidence of viral replication, persistently elevated serum alanine aminotransferase levels, and histologic evidence of active inflammation and/or fibrosis.

According to a company news release, the decision applies to all 27 countries of the EU and to Iceland and Norway. Launches are expected to begin during the second quarter of 2007, initially in the United Kingdom and Germany.

EC approval was based primarily on 52-week data from a phase 3 international clinical trial (GLOBE) of 1367 patients, showing that telbivudine yielded significantly greater HBV DNA decreases from baseline than lamivudine. Efficacy was demonstrated both in hepatitis B e antigen (HBeAg)-positive and HBeAg-negative patients (-6.5 log10 vs -5.5 log10 and -5.2 log10 vs -4.4 log10; P < .01 for both).

Also, significantly more telbivudine-treated patients achieved clearance of detectable HBV DNA (polymerase chain reaction (PCR)-negative) at 52 weeks than lamivudine-treated patients (HBeAg-positive patients, 60% vs 40%; HBeAg-negative patients, 88% vs 71%; P < .01 for both).

Therapeutic response was evaluated as a primary composite end point of viral suppression (serum HBV DNA suppression < 100,000 copies/mL) with either alanine aminotransferase normalization or loss of detectable HBeAg. Although therapeutic response was significantly higher in HBeAg-positive patients treated with telbivudine vs lamivudine (75% vs 67%; P < .05), HBeAg-negative patients responded similarly to both treatments (75% vs 77%).

Telbivudine was also associated with significantly less viral resistance and treatment failure than lamivudine therapy, and fewer (4% vs 8%) and less severe resistance-associated elevations in serum ALT levels were also observed. These "flares" can cause potentially fatal liver failure in patients with HBV.

“Sebivo works very quickly, suppressing HBV to undetectable levels (ie, PCR negativity) in more than half of patients at 6 months of treatment,” the company notes in a news release, pointing out that 95% of patients who achieved PCR negativity within this time retained their undetectable virus levels at 1 year. “Preliminary 2-year results from the GLOBE trial, completed after the EU submission, demonstrated that these benefits were maintained through 2 years of treatment.”

The nature and frequency of adverse events were similar for both groups and most commonly included upper respiratory infection (14% vs 13%), headache (11% vs 13%), fatigue (12% vs 10%), and nasopharyngitis (11% vs 10%). Transient creatine kinase elevations were more common in the telbivudine group (9% vs 3%) but did not require treatment modification.

Telbivudine (Tyzeka) was approved by the FDA on October 25, 2006. As Sebivo, it was approved earlier this year by Switzerland's regulatory agency, Swissmedic; Health Canada; and China’s State Food and Drug Administration.

Self-Heating Lidocaine/Tetracaine Patch (
Rapydan) for Topical Anesthesia in Sweden

On April 19, Sweden’s Medical Products Agency approved a lidocaine/tetracaine 70-mg/70-mg local anesthetic patch ( Rapydan, Zars, Inc [marketed by EUSA Pharma]) for use on intact skin to provide topical anesthesia for needle puncture in patients 3 years and older and for superficial surgical procedures in adults.

The patch is applied 30 minutes prior to the puncture or procedure, and consists of a thin, uniform layer of local anesthetic emulsion with an integrated oxygen-activated heating component. This patented technology, known as controlled heat-assisted drug delivery, causes the patch to begin heating upon removal from the storage pouch and is intended to enhance analgesic delivery to the skin.

The analgesic patch should not be used for a duration longer than recommended, and is contraindicated in patients with a known sensitivity to lidocaine, tetracaine, or local anesthetics of the amide or ester type. In clinical trials, local skin reactions (erythema, blanching, edema) were the most commonly reported patch-related adverse events.

According to a company news release, the lidocaine/tetracaine patch is expected to be commercially available in Sweden by mid 2007 and in additional European countries later this year, pending additional regulatory approvals. Marketed as Synera in the US, it was approved by the FDA in July 2005 for use on intact skin to provide local dermal analgesia for superficial venous access and dermatologic procedures, such as excision electrodessication and shave biopsy of skin lesions.


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