Date: 2013-11-09
Type of information: Results
phase: 3
Announcement: results
Company: Merck&Co (USA) ALK Abello (Denmark)
Product: MK-7243 (Grazax® in Europe - grass allergy immunotherapy tablet)
Action
mechanism: immunotherapy product. Grazax® is a fast-dissolving, once daily allergy immunotherapy tablet (AIT) for home treatment of grass pollen allergy. Grazax® works by inducing a protective immune response and offers patients sustained relief of their allergy symptoms.
Disease: grass pollen allergy
Therapeutic area: Respiratory diseases - Allergic diseases
Country:
Trial
details: This multicenter, double-blind, randomized, placebo-controlled, parallel-group study evaluated the efficacy and safety of the investigational MK-7243 sublingual tablet (2800 BAU) in 1,501 pediatric and adult patients (ages 5-65) with a clinical history of Timothy grass pollen-induced allergic rhinitis with or without conjunctivitis, with or without asthma (FEV1 ?70 percent of predicted value). As baseline characteristics, 25 percent of patients in the study had asthma; patients with a history of severe asthma were excluded. Additionally, 85 percent of patients in the study were sensitized to multiple allergens. Patients received either MK-7243 or placebo once daily for at least 12 weeks prior to and during the grass pollen season.
The primary efficacy assessment of the study was total combined score (TCS), which was the sum of the rhinoconjunctivitis daily symptom score (DSS) and the daily medication score (DMS) averaged over the entire grass pollen season. The DSS consisted of daily ratings of four nasal symptoms (runny nose, blocked nose, sneezing and itchy nose) and two eye symptoms (gritty eyes and watery eyes) on a scale from zero (no symptoms) to three (severe symptoms). The DMS was based on the type and amount of allergy rescue medication (oral antihistamines, ocular antihistamines, intranasal corticosteroids or oral corticosteroids) used each day during the grass pollen season, which patients in both arms of the study were permitted to use.
Four key secondary endpoints included the average rhinoconjunctivitis DSS over the entire grass pollen season, the average rhinoconjunctivitis DMS over the entire grass pollen season, the average rhinoconjunctivitis TCS over the peak grass season, and the average overall score for the Rhinoconjunctivitis Quality of Life Questionnaire with Standardized Activities for Subjects ?12 Years of Age (RQLQ(S)12+) over the peak grass pollen season. Safety endpoints included reported adverse events.
Latest
news: Merck&Co initiated the trial in 2011 to evaluate the efficacy and safety of grass AIT versus placebo in the treatment of grass pollen induced allergic rhinoconjunctivitis (hay fever). The primary endpoint was the combined rhinoconjunctivitis daily symptom score (DSS) and rhinoconjunctivitis daily medication score (DMS) during the grass pollen season. The trial, which included approximately 1,500 patients, is the largest study of grass AIT to date. * On November 9, 2013, ALK's partner for North America, Merck&Co has reported that data from a pivotal Phase III clinical trial with its investigational grass sublingual allergy immunotherapy (AIT) tablet were presented at the 2013 annual meeting of the American College of Allergy, Asthma & Immunology (ACAAI) in Baltimore, USA during 7-11 November. Results showed that MK-7243 demonstrated significant improvement in Total Combined Score (TCS) averaged over the entire grass pollen season (the primary endpoint), which was the sum of the rhinoconjunctivitis daily symptom score (DSS) and the daily medication score (DMS), compared to placebo.
In this study, patients treated with MK-7243 (n=629) showed a 23 percent improvement in TCS relative to placebo (n=672) over the entire grass pollen season (median difference: -0.98, P < .001). Additionally, patients treated with MK-7243 demonstrated a 20 percent improvement in DSS over the entire grass pollen season (median difference: -0.64, P =.001), and a 35 percent improvement in DMS over the entire grass pollen season (mean difference: -0.48, P<.001). During the peak grass pollen season, patients treated with MK-7243 demonstrated a 29 percent improvement in TCS (median difference: 1.33, P<.001), and a 12 percent improvement in RQLQ (median difference: -0.13, P=.027).
The most frequently reported adverse events in the study for MK-7243 (n=753) versus placebo (n=745) were local site reactions: throat irritation 23 percent vs. 4 percent, oral pruritus 19 percent vs. 3 percent, oral paraesthesia 12 percent vs. 3 percent, mouth edema 13 percent vs. 1 percent and ear pruritus 12 percent vs. 1 percent, respectively. No serious treatment-related adverse events were reported. Three patients (2 MK-7243, 1 placebo) had moderate systemic allergic reactions. Symptoms resolved without treatment for the two patients who received MK-7243, and both of these patients discontinued treatment. Four different patients (3 MK-7243, 1 placebo) were administered epinephrine. Two of the four epinephrine administrations (1 MK-7243, 1 placebo) were reported as unrelated to the study medication. Of the remaining two administrations for patients who received MK-7243, one was deemed possibly related to the study medication and the other was deemed probably related.
These results reflect data from the full analysis set, which included randomized patients who took at least one dose of study medication and had at least one efficacy measurement in the corresponding evaluation period (entire grass pollen season or peak grass pollen season).
Earlier this year, Merck announced that the FDA had accepted for review Biologics License Applications for its investigational Timothy grass sublingual allergy immunotherapy tablet and its ragweed sublingual allergy immunotherapy tablet. Merck expects the FDA’s review for both to be completed in the first half of 2014. Merck has partnered with ALK-Abello to develop its sublingual allergy immunotherapy tablets for Timothy grass pollen, ragweed pollen and house dust mite induced allergic rhinitis in North America.
* On December 22, 2012, ALK Abello has announced that a Phase III clinical trial of its investigational sublingual grass allergy immunotherapy tablet (AIT) met its primary efficacy endpoint. The trial was conducted by ALK\'s strategic partner, Merck&Co. Known as Grazax® in Europe, the product has been licensed by ALK to Merck for North America.
The study was designed to form a pivotal part of the submission package for Merck’s filing of a registration application for grass AIT with the FDA. Merck has informed ALK that the new data supports and confirms the planned filing of the registration application with the FDA in 2013.
Merck&Co and ALK have a strategic partnership to develop, register and commercialise a portfolio of allergy immunotherapy tablets against grass, ragweed and house dust mite allergy in the USA, Canada and Mexico.
In addition to the registration studies for grass AIT in the USA, Merck&Co has undertaken a series of other important steps under the partnership to commercialise the tablet portfolio, including:
Ragweed: The successful completion of two Phase III clinical trials with ragweed AIT, which both consistently met the primary efficacy endpoints of reducing allergy symptoms and concomitant medication use. Recently, Merck&Co also completed an additional safety trial in 900 patients. The results supported Merck\'s plans for filing of a registration application with the FDA in 2013.
House Dust Mite (HDM): In October 2012, Merck&Co initiated a Phase IIb clinical trial for HDM AIT (known as MITIZAX® in Europe and Japan). The purpose is to evaluate dose-related effectiveness, safety and tolerability of HDM AIT compared to placebo in the treatment of HDM-induced allergic rhinitis and rhinoconjunctivitis in adults.
Additionally, Merck&Co has recently disclosed that they are planning to initiate a Phase III clinical trial involving about 1,500 patients, which is expected to complete in 2015. Approximately 45% of allergy sufferers in North America are affected by the non-seasonal HDM allergen.
