默沙东提摩西草舌下过敏免疫含片MK-7243显著减少过敏症状

默沙东（Merck & Co）近日公布了实验性提摩西草（Timothy）舌下过敏免疫含片（MK-7243）III期研究的数据。该项研究，涉及1501例北美成人和儿童患者。数据表明，与安慰剂相比，MK-7243显著改善了整个花粉季节平均总复合得分（TCS），达到了研究的主要终点。研究中，TCS为鼻结膜炎（rhinoconjunctivitis）日常症状评分（DSS）和日常药物评分(DMS)之和。相关数据将提交至11月7日-11日在巴尔的摩举行的美国过敏哮喘与免疫学会年度科学会议。

MK-7243是一种每日一次的实验性提摩西草（Timothy）舌下过敏免疫含片，旨在帮助产生一种免疫反应，来帮助保护患者对提摩西草花粉的过敏，从而帮助治疗过敏性鼻炎的根本原因。

默沙东于今年早些时候宣布，FDA已接受审查其提摩西草舌下过敏免疫片剂和豚草舌下过敏免疫片剂的生物制品许可申请（BLA）。默沙东预计，FDA将与2014年上半年完成审查。

英文原文：Merck’s Investigational Grass Sublingual Allergy Immunotherapy Tablet Significantly Reduced Allergy Symptoms and Need for Symptom-Relief Medication in Adults and Children in Pivotal Phase III Study

WHITEHOUSE STATION, N.J.--(BUSINESS WIRE)--Merck (NYSE:MRK), known as MSD outside the United States and Canada, today announced data for its investigational Timothy grass sublingual allergy immunotherapy tablet (MK-7243) from a study involving 1,501 North American adult and pediatric patients. 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. Researchers will present findings at the American College of Allergy, Asthma & Immunology Annual Scientific Meeting, Nov. 7-11, in Baltimore.

“Patients in this study who took the investigational Timothy grass sublingual allergy immunotherapy tablet showed a significant improvement in common allergy symptoms during the entire grass season,” said Dr. David Bernstein, professor of Medicine and Environmental Health, Division of Immunology, Allergy and Rheumatology, University of Cincinnati College of Medicine, who was one of the study investigators.

“Few large studies have evaluated sublingual immunotherapy for allergic rhinitis in both adults and children, and we are proud that Merck is exploring this potential new option for Timothy grass pollen-induced allergic rhinitis treatment in North America,” said Dr. Sean Curtis, vice president, Respiratory and Immunology, Merck Research Laboratories.

Study design

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.

Study results

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).

These results will be presented in a poster titled “Efficacy and Safety of MK-7243: A Grass Sublingual Immunotherapy Tablet Treatment in a Large Randomized Controlled Trial in North American Children and Adults” on Saturday, Nov. 9 from 12:30 – 1:30 p.m. ET and Sunday, Nov. 10 from 12:30 – 1:30 p.m. ET.

In addition, a pre-specified sub-group analysis of the data from this clinical trial will be presented in a poster titled “Treatment with MK-7243, a Grass Sublingual Immunotherapy Tablet, is Associated with Similar Efficacy and Safety in Children and Adults: Findings from a Subgroup Analysis of Data from a Large North American Trial” on Saturday, Nov. 9 from 12:30 – 1:30 p.m. ET and Sunday, Nov. 10 from 12:30 – 1:30 p.m. ET.

Merck's investigational sublingual allergy immunotherapy tablet program

Merck's Timothy grass sublingual allergy immunotherapy tablet is an investigational once-daily tablet that dissolves under the tongue and is designed to help treat the underlying cause of allergic rhinitis by generating an immune response to help protect patients against Timothy grass pollen.

Earlier this year, Merck announced that the U.S. Food and Drug Administration (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.