Boehringer Ingelheim’s Spiriva (tiotropium bromide) was launched in the US, Japan and four of the five major European markets (France, Germany, Italy, Spain and the UK) between 2002 and 2004. The product was launched in France in 2006, after delays relating to pricing negotiations. Spiriva is the only long-acting bronchodilator specifically marketed for COPD and is the only long-acting anticholinergic (LAMA) on the market, making it the gold standard in COPD treatment.
In 2010, company reported sales of the drug reached $4.1bn (€2.9bn) (Boehringer Ingelheim, 2011; http://www.boehringer-ingelheim.com). Spiriva has been very popular since its launch due to the high unmet needs in COPD, and sales have grown continuously in each of the seven major markets over the last 5 years. In December 2009, the FDA approved Spiriva for the additional indication of the reduction of exacerbations in patients with COPD (Boehringer Ingelheim, 2010; http://www.boehringer-ingelheim.com). This added indication is expected to contribute to the continued strong upward sales trend of the drug in the US. However, the threat of direct competitors in the form of novel once-daily LAMAs, the imminent launch of LABA/LAMA combination products and the expected market entry of generic tiotropium bromide will impact Spiriva’s sales considerably over the next 10 years.
In July 2010, Boehringer Ingelheim published a pooled analysis of clinical trials of Spiriva Respimat, which highlighted a numerically greater incidence of fatal events in patients that had been treated with Spiriva Respimat compared to placebo in six trials (Boehringer Ingelheim, 2010b; http://trials.boehringer-ingelheim.com). Datamonitor believes that it is these safety concerns which are holding back the roll-out of the Respimat in additional countries.
“I think it is completely unexpected and unexplained at the moment… I think now that a concern has been raised I am sure the regulators are going to say they have got to have the safety data. I am sure the FDA is asking for it … and I imagine the EU would be the same.” – EU key opinion leader.
Large-scale study comparing Respimat with HandiHaler underway
In September 2008, Boehringer Ingelheim received a Complete Response Letter from the FDA seeking additional data on the Respimat (Pfizer, 2008; http://media.pfizer.com). 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. As a similar result has not been seen for patients treated with the HandiHaler, Boehringer Ingelheim has initiated a large-scale 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 affects on exacerbations when compared to the HandiHaler. The multi-center study will include nearly 17,000 patients and is randomized, active-controlled and double-blind. It is expected to be completed in December 2013.
Olodaterol/tiotropium (Boehringer Ingelheim)
Boehringer Ingelheim is developing an inhaled combination of olodaterol (BI1744), a LABA, and Spiriva (tiotropium bromide), currently the only marketed LAMA, for the potential treatment of COPD. With companies such as GlaxoSmithKline and Novartis developing novel once-daily bronchodilators and bronchodilator combinations, Boehringer Ingelheim’s combination will help to extend the life of the market-leader Spiriva, and defend the company against competition. However, the combination is not expected to be the first LABA/LAMA to reach the market, which is a key disadvantage.
Datamonitor assumes that it will take at least 2 years for the Phase III clinical trial program, such that the company will be able to file for approval of the drug in the US and EU around Q2 2013, with the drug forecast to launch in Q3 2014. A launch in Japan is forecast to occur 2 years later, at the end of 2016.
Datamonitor’s forecast for olodaterol/tiotropium is based on a best-case scenario, with a positive outcome for the Phase II dose-ranging study and subsequent Phase III program. Furthermore, it is assumed that the drug will continue to be developed for use with the Respimat inhaler, and therefore that the safety concerns regarding the device will be resolved by the time of launch.
“The problem for Boehringer is that they want to use [the Respimat] for other drugs and, in particular, for a combination, so it is not just for the tiotropium it is really for the future drugs … the obvious thing to do is to combine olodaterol and tiotropium, which is why I think they are keen to save the Respimat.” – EU key opinion leader