ERS 2012: Spiriva celebrates 10th anniversary with new data in both COPD and asthma.
ERS 2012: Spiriva celebrates 10th anniversary with new data in both COPD and asthma
COPD therapy Spiriva has celebrated its 10th anniversary with the presentation of additional data at the 2012 annual meeting of the European Respiratory Society in Vienna, Austria. New data were presented for both COPD, for which the drug is widely established, and for asthma, for which it is in Phase III studies with the aim of providing an alternative treatment option for uncontrolled patients.
Over the years Boehringer Ingelheim has undertaken numerous post-marketing studies and amassed a large collection of data on Spiriva (tiotropium; Boehringer Ingelheim), helping to cement its role as the gold-standard therapy in chronic obstructive pulmonary disease (COPD). Boehringer Ingelheim has stated that the drug has been in more than 175 clinical trials for COPD and has over 25 million patient years of experience. As the first once-daily bronchodilator and the only long-acting anticholinergic on the market, Spiriva is well established with physicians and patients and has faced little direct competition.
While some new data were presented at the 2012 European Respiratory Society (ERS) conference for Spiriva in COPD, the most notable data were for asthma. Boehringer Ingelheim is looking to asthma to extend the lifecycle of Spiriva, and the company presented data from the PrimoTinA-asthma Phase III studies which look at the effect of tiotropium on patients who remain symptomatic despite treatment with at least inhaled corticosteroids and long-acting beta 2 agonists. The studies were two identical double-blind parallel-group trials that included asthma patients with post-bronchodilator forced expiratory volume in one second (FEV1) <80% predicted and an asthma control questionnaire score greater than or equal to 1.5. The trials included 912 patients who, in addition to maintenance therapy, received either tiotropium 5mcg or placebo for 48 weeks. The trials had three primary endpoints: peak FEV1 at 24 weeks, trough FEV1 at 24 weeks, and time to first severe exacerbation.
The trials met the first two primary endpoints as the addition of tiotropium significantly improved lung function at 24 weeks, and sustained to 48 weeks. The third endpoint was based on a prespecified combined analysis of the two trials. The addition of tiotropium therapy was associated with a 21% risk reduction in time to first severe exacerbation. The studies further showed that the addition of tiotropium reduced the risk of any exacerbation and there were significant improvements in asthma control and asthma-related quality of life.
These results are highly encouraging, particularly as tiotropium demonstrated significant efficacy despite the fact that all patients were already receiving optimal maintenance therapy as defined by the Global Initiative for Asthma guidelines. Spiriva could therefore be an effective treatment option for uncontrolled patients, among which there remains a high unmet need.
These studies were part of Boehringer Ingelheim’s Phase III program for asthma, which will include 4,000 patients across adult, pediatric, and adolescent populations who are symptomatic despite treatment with steroids.
In these trials, tiotropium is delivered via the Respimat, a soft mist inhaler. The Respimat was the second device to be developed for Spiriva, the first being the HandiHaler, a dry powder inhaler. The Respimat was first made available in Germany and the UK in 2007 and is considered to be an easy-to-use and valued device. However, while some additional roll-out has been seen in the EU, the device has so far failed to gain approval in the US.
In September 2008 the company received a Complete Response Letter from the FDA seeking additional data on the Respimat. This was followed in July 2010 by the release of pooled safety results showing an increase in all-cause mortality in patients treated with the Respimat compared to placebo. The data highlighted a numerically greater incidence of fatal events in patients that had been treated with Spiriva Respimat compared to placebo in six trials. In response, Boehringer Ingelheim has initiated a large-scale global Phase III safety study comparing Spiriva delivered in each of the devices. The trial is designed to show that Spiriva delivered by the Respimat has a similar effect on safety and similar or superior effects on exacerbations when compared to the HandiHaler. The multicenter study includes around 17,000 patients and is randomized, active controlled, and double blind. It is expected to be completed in April 2013.
Given the wide experience already gained with Spiriva in the HandiHaler, it is somewhat surprising to see Boehringer Ingelheim opting to develop Spiriva for asthma in the Respimat. This could be a sign that Boehringer Ingelheim is confident that the safety trial will dispel fears surrounding the Respimat and that the company remains keen on bringing the Respimat to the US market.
Spiriva has so far faced little direct competition, allowing it to see high commercial success in COPD. Datamonitor forecasts 2012 sales to reach $3bn across the seven major markets (the US, Japan, France, Germany, Italy, Spain, and the UK). However, with the COPD pipeline increasingly active, and with the looming threat of generics, Boehringer Ingelheim is looking at ways to maintain its dominance. Datamonitor forecasts 11 new products to launch for COPD over the next 10 years, dramatically increasing competition.
Unlike in COPD where Spiriva is used across all disease severities, if approved for asthma its use will likely be limited to the uncontrolled segment of the population, which key opinion leaders interviewed by Datamonitor estimate could be up to 10% of patients. However, within that uncontrolled asthma patient population, there is high unmet need which could allow for a rapid adoption of the brand, and allow Spiriva access to a niche market with limited competition.