根据3月4日公布的一项IIb临床实验数据，罗氏（Roche）开发的实验性单抗药物lebrikizumab，使严重不受控哮喘患者的哮喘发作降低了60%，并帮助改善了特定患者群体的肺功能，预示着lebrikizumab有望成为特定哮喘群体的首个个性化治疗药物。
lebrikizumab由罗氏旗下基因泰克（Genentech）研制。该项IIb期试验，在463例经高剂量吸入性糖皮质激素及二线哮喘控制疗法均无法充分控制病情的哮喘患者中，调查了3种剂量lebrikizumab（37.5mg，125mg，250mg）的疗效。
根据汇总数据，罗氏发现，在骨膜素蛋白（periostin）高水平表达的患者群体，与安慰剂相比，lebrikizumab使哮喘发作降低了60%。而在低水平骨膜素蛋白的患者群体中，与安慰剂相比，lebrikizumab仅使哮喘发作降低了5%。
该项研究的主要研究员之一Nicola Hanania在接受电话采访时称，若获得批准，lebrikizumab将成为首个个性化药物，可用于经其他疗法治疗病情仍不受控制的特定哮喘群体。
Lebrikizumab通过阻断白介素13（IL-13）发挥作用，IL-13是一种炎性细胞因子，与呼吸道炎症和粘液产生有关。骨膜素（periostin）被认为是IL-13活动的一个生物标志物，同时也是一种可能的预测因子，能够帮助评价lebrikizumab的疗效。
目前，罗氏也正在开发一种骨膜素血液检测试剂盒，以帮助鉴别最有可能从lebrikizumab治疗（每4周注射1次）中受益的患者群体。
(Reuters) - An experimental drug reduced asthma attacks in patients with severe uncontrolled asthma by 60 percent and helped improve lung function in certain patients, indicating that the drug could offer the first personalized approach to treatment, according to data from a clinical trial released on Tuesday.
The biotech drug lebrikizumab, which was developed by Roche Holding's Genentech unit, was tested at three doses in patients whose asthma was not sufficiently controlled even with high-dose, inhaled corticosteroids and a second asthma-controlling therapy.
In the 463-patient Phase IIb study, lebrikizumab reduced asthma attacks by a statistically significant 60 percent more than a placebo in patients found to have a high level of the protein periostin, according to pooled data from the three doses tested - 37.5 milligrams, 125 mg and 250 mg. That compared with a 5 percent reduction versus placebo over 28 to 52 weeks of treatment in those with low levels of periostin.
"If this drug gets approved we would have for the first time a personalized approach other than just blanket therapy for everyone with uncontrolled disease," Dr Nicola Hanania, one of the study's lead investigators, said in a telephone interview.
Lebrikizumab works by blocking interleukin-13, or IL-13, which contributes to airway inflammation and mucous production. Periostin is believed to be a biomarker for IL-13 activity and a likely predictor of how well the Roche drug will work.
Roche is also developing a blood test for periostin in order to identify the patients most likely to benefit from lebrikizumab, which is injected once every four weeks.
Hanania, who is director of the Asthma Clinical Research Center at Baylor College of Medicine in Houston, called the data from the study "very exciting."
In those with severe asthma receiving existing treatments, "we still see patients who still have symptoms, who still have exacerbations, hospital admissions, and this is the type of patient this study was targeting," he said.
Curiously, the greatest level of asthma attack reduction, at 81 percent, was seen with the lowest dose of lebrikizumab, something that Hanania called surprising. Hanania, who presented the data at the American Academy of Allergy, Asthma and Immunology (AAAAI) meeting in San Diego, noted, "Higher is not always the better."
Fifteen percent of the estimated 25 million Americans with asthma suffer from severe asthma, according to the National Institutes of Health. About half of severe asthmatics are believed to have high periostin levels.
Among patients with high level periostin, the drug improved lung function by 9.1 percent after 12 weeks, compared with an improvement of just 2.6 percent in the low periostin group.
Lung function was tested by change in FEV1, a measure of the maximum amount of air that can be forcibly exhaled in one second. The greatest improvement in FEV1, of 10.7 percent, was seen with the 125 mg dose of lebrikizumab.
"Statistically it's significant, and I believe it is clinically significant because it goes hand in hand with reduction in exacerbations," Hanania said of the lung function improvement seen in the high periostin group.
The incidence of serious adverse side effects was low and similar in the lebrikizumab and placebo arms of the study, researchers said.
"The safety profile was very reassuring. Nothing really stood out as major side effect or major serious adverse effect," Hanania said.
If the results are replicated in large, ongoing Phase III trials that will include more than 2,000 patients, Roche said it expects to seek approval for the drug in 2016.
"As a clinician, this is important because there is a great need for additional therapy for those with poorly controlled asthma," Hanania said. "It's a light at the end of the tunnel."
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