AAAAI: Sublingual Pill Cuts Grass Pollen Allergy
|Median symptom scores were 37% lower with Grazax compared with placebo after three years of treatment (P=0.0001), Waltraud Emminger, M.D., of Allergie-Ambulatorium Rennweg in Vienna, Austria, told attendees at the American Academy of Allergy, Asthma, and Immunology meeting.
Moreover, participants taking Grazax used 60% less antihistamine and steroid medication in the study’s third year relative to the placebo group ( P<0.003).
“Grazax resulted in a highly significant reduction of rhinoconjunctivitis symptoms and use of rescue medication in all treatment years,” Dr. Emminger said.
Grazax, available in Europe but not in the U.S., is a fast-dissolving sublingual tablet taken once a day. A clinical trial to support U.S. approval of the immunotherapy is now underway.
The randomized, phase III study reported by Dr. Emminger began several months before the 2005 grass pollen season and included 634 patients in eight European countries. Active treatment ended in 2007 but the study remains blinded and participants will be followed through 2009.
Adults 15 to 65 years old were included in the trial if they had a minimum two-year history of confirmed grass pollen allergy, no other perennial or seasonal allergies that overlapped with grass pollen season, and FEV1 lung function values of at least 70% predicted.
The investigators set no limits on participants’ use of antihistamine and steroid drugs. Participants recorded their symptoms and rescue medication usage daily on handheld computers.
“This was a real test for [the Grazax] tablet,” Dr. Emminger said.
In the 2007 season, median rhinovirus symptom scores were 3.2 for patients taking placebo compared with 2.0 for those taking Grazax.
The percentage difference was nearly identical in the 2005 and 2006 seasons, although the absolute symptom scores declined in both groups as time went on.
Dr. Emminger said this resulted from a combination of reduced average pollen counts and different patterns in rescue medication usage.
Adverse effects were extremely common with Grazax during the first year, with 81% of patients reporting an average of two treatment-emergent events each. In the placebo group, 23% of patients reported adverse effects.
The effects with Grazax were generally mild oral and esophageal reactions that vanished after two weeks in most patients.
By the third year, Grazax still appeared to cause more adverse effects than placebo, but the difference was less stark. Only 19% of patients receiving Grazax reported adverse effects in 2005, compared with 9% of the placebo group.
Dr. Emminger explained that the Grazax regimen is unlike most other allergic immunotherapies, which start with small doses and gradually build up.
With Grazax, patients start with the full dose from day one, she said.
She said that fewer than 1% of patients in both groups discontinued because of adverse effects.
The product’s U.S. sponsor, Schering-Plough, is now backing a phase III trial with results expected in September 2009, thus covering the next two pollen seasons, a company spokeswoman said.
It’s the second try for Schering-Plough and ALK-Abello, the Danish firm that developed Grazax. An earlier phase III trial ended last year with Grazax failing to meet the primary endpoint of significant symptom reduction relative to placebo.
Neither treatment group showed an increase in symptoms during pollen season, making it impossible to find a difference, according to ALK-Abello.
|Primary source: AAAAI Meeting
Emminger W, et al “The long-term efficacy and safety of a grass allergen tablet for sublingual immunotherapy: Findings from a 3-yr clinical trial” J Allergy Clin Immun 2008; 121:S75.