Alvesco

Product
Alvesco

Approval Date
January 15, 2008

Release Date
Second half 2008

Company
Sepracor

Class
Inhaled corticosteroid with novel release and distribution properties.

Indication
For the maintenance treatment of asthma and as prophylactic therapy in adult and adolescent patients aged 12 years and older.

Active Ingredient
Ciclesonide inhalation aerosol; 160-microgram and 80-microgram inhaler.

Agency Roster
Saatchi & Saatchi Healthcare Advertising (professional)
Spectrum Science Communications (PR)

Marketing Strategy/Execution
Analysts say Alvesco may offer advantages over existing inhaled corticosteroids, and Sepracor’s decision to in-license the product in the US helps Nycomed overcome a major commercial hurdle. The privately-owned Swiss company, which bought Alvesco developer Altana last year, has no US sales force. Alvesco was originally to be co-marketed by Sanofi-Aventis. Multiple handoffs, and an approvable letter in October 2004, hampered its ability to make it to market. Sepracor plans to launch in the second of half of 2008, following the spring release of Omnaris, a nasal spray formulation of ciclesonide approved in 2006.

Taken once daily, Alvesco’s efficacy is comparable to other existing inhaled corticosteroids, such as budesonide and fluticasone propionate, that are taken twice daily. However, the nasal spray corticosteroid market is a crowded one, with at least four major players. Fluticasone (Flonase) is generic and accounts for about 45% of prescriptions. Advair is widely used in the asthma maintenance setting and could become generic in 2011.  UPDATE: Sepracor has launched a nasal spray formulation of ciclesonide, called Omnaris, for treating seasonal allergic rhinitis (5/08).

The Market

Physician Outlook
Approved by the FDA in January 2008, Alvesco (ciclesonide) Inhalation Aerosol is indicated for the maintenance treatment of asthma and as prophylactic therapy in adult and adolescent patients aged 12 years and older. It is produced by Nycomed, which is in active negotiations with possible marketing partners for US commercialization. Prior to launch, physician awareness and expectations were fairly high for this inhaled corticosteroid with a profile similar to Schering-Plough’s Asmanex (mometasone furoate). Clinical studies revealed the drug may lead to low systemic absorption, a relative unmet need in the asthma category. GfK Market Measures’ 2007 Asthma MD study, fielded in September, revealed high levels of awareness and clinical experience among pulmonologists and allergists, and both specialties rated it relatively high in anticipated usefulness to treat asthma symptoms.

—Sue Ramspacher, SVP, GfK Market Measures, Jan. 2008

Also in the Pipeline (According to Adis R&D Insight)
Drug: Flutiform
Manufacturer: SkyePharma PLC
Indication:  Asthma
Active Ingredient:  Formoterol/fluticasone propionate
Phase: III

Drug: Asmanex/Foradil
Manufacturer: Novartis
Indication:  Asthma
Active Ingredient: Mometasone/formoterol
Phase: III

Drug: Azmacort HFA
Manufacturer: Kos Pharmaceuticals
Indication:  Asthma
Active Ingredient: Triamcinolone acetonide hydrofluoroalkane
Phase: III
Source:Wolters Kluwer Health

Recent MM&M Coverage
Pipeline 2008 – Medical Marketing and Media
The Top 60: Saatchi & Saatchi Healthcare Communications
People, Product and Agency News from the Nov. 5 MM&M News Brief
Altana to dismantle sales, marketing team
Pfizer sues Sanofi-Aventis over Exubera marketing deal
Product news
Omnaris
Nycomed finds a US partner for asthma drug
Product news

Pharmacology
Alvesco is a metered-dose oral inhaler product with a dose counter that delivers ciclesonide, a non-halogenated corticosteroid, to the airways using HFA- 134 as a propellant. Ciclesonide is a prodrug that is hydrolized to its active metabolite, des-ciclesonide, which is further metabolized in the liver to other active metabolites.  The exact mechanism of action of corticosteroids in the management of asthma is unknown, however they have been shown to have a wide range of activity against mediators of inflammation involved in the inflammatory response seen with asthma.

Clinical Trials
Six randomized, double-blind, placebo controlled studies were conducted to evaluate the efficacy of Alvesco in the management of mild to severe asthma in patients =12 years of age.

In patients previously treated with bronchodilators alone, subjects treated with Alvesco had significant improvements in the morning pre-dose FEV1 at week 16. For this and other measures of asthma control and the need for rescue albuterol, the improvement was greatest in patients given 80mcg twice daily compared to those using 160mcg once daily.

In patients previously maintained on inhaled corticosteroids, the FEV1 was improved, and asthma symptom scores, AM PEF, and decreased need for rescue albuterol remained stable at 12 weeks for those receiving Alvesco versus those given placebo.

For patients previously maintained on oral corticosteroids, patients using Alvesco 320mcg or 640mcg twice daily significantly reduced their prednisone needs by 47% and

62%, respectively, compared to those on placebo, whose prednisone needs increased by 4%. There was no significant difference seen with Alvesco 640mcg twice daily compared to 320mcg twice daily.

Adverse Reactions
Headache, nasopharyngitis, sinusitis, throat pain, upper respiratory infection, arthralgia, nasal congestion, back pain; rare: bronchospasm, immunosuppression, glaucoma, cataracts, oral candidiasis, decreased bone mineral density.

Adults
Previously on bronchodilators alone: initially 80mcg twice daily, max 160mcg twice daily. Previously on inhaled corticosteroids: initially 80mcg twice daily; max 320mcg twice daily. Previously on oral corticosteroids (see literature): 320mcg twice daily. Rinse mouth after use; avoid eyes.

Children
Not recommended.

Contraindications
Not for primary treatment of acute heart attack.

Precautions
Infections. If exposed to chickenpox or measles, consider immuneglobulin prophylactic therapy. If adrenal insufficiency exists following systemic corticosteroid therapy, replacement with inhaled corticosteroids may exacerbate symptoms of adrenal insufficiency (eg, lassitude). Monitor for hypercorticism and HPA axis suppression (if occur reduce dose gradually). Monitor for growth suppression in children. Monitor for changes in vision, increased intraocular pressure, cataracts. Pregnancy (Cat.C). Nursing mothers.