COPD Review: Spiriva Respimat safety data and GSK’s LABA.
By Natasha Spiller, Analyst
13 September 2013
I am an Analyst at Datamonitor Healthcare. After joining the company in 2012, I have produced analysis across a number o...
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With a market predicted to be worth $11bn in 2022, it is no wonder that big pharma have taken a keen interest in chronic obstructive pulmonary disease (COPD).
It has been an eventful week for key players in this disease area: new safety data emerged for Spiriva Respimat (tiotropium; Boehringer Ingelheim) from this year’s European Respiratory Society (ERS) Annual Congress while Anoro (umeclidinium/vilanterol), GlaxoSmithKline’s fixed-dose long-acting beta 2 agonist/long-acting muscarinic antagonist (LABA/LAMA) inhaler, has been recommended for approval by the US FDA Pulmonary-Allergy Drugs Advisory Committee (PADAC).
Boehringer Ingelheim’s continued dominance is bolstered by safety data for Spiriva Respimat
At the ERS Annual Congress this year, Boehringer Ingelheim presented data from the TIOSPIR (Tiotropium Safety and Performance in Respimat) trial, which demonstrated that Spiriva Respimat is comparable to Spiriva HandiHaler in terms of both safety and efficacy. The data (also published in the New England Journal of Medicine) will support any future regulatory application for Spiriva Respimat in the US. Importantly, they will also support Boehringer Ingelheim’s portfolio of COPD therapies that have been developed in the Respimat device. This includes olodaterol Respimat, currently under regulatory review in the US, and the pipeline LABA/LAMA inhaler olodaterol/tiotropium.
Although Spiriva has seen great success within the market, the strength of its position will be eroded by the emergence of the new LABA/LAMA drug class and the threat of generic tiotropium inhalers. The continued development of Boehringer Ingelheim’s portfolio using the Respimat device, now supported by new safety data, is critical so that the company can maintain its stronghold within the COPD market.
To quash safety concerns for the Respimat device, Boehringer Ingelheim initiated a large-scale clinical trial (TIOSPIR) which involved over 17,000 patients and compared the efficacy and safety of Spiriva Respimat with the Spiriva Handihaler device. The Respimat is a soft mist inhaler while the HandiHaler is a dry powder inhaler. Use of Spiriva Respimat (at 5mcg once daily) compared to Spiriva Handihaler (18mcg) led to a similar impact on all-cause mortality. The two inhaler types were comparable in terms of the efficacy measures of time to first COPD exacerbation, exacerbation frequency, and rate of COPD exacerbations associated with hospitalization.
Spiriva Respimat has not been approved in the US. In 2008, Boehringer Ingelheim received a Complete Response Letter from the FDA requesting further data for the inhaler. Safety concerns for Spiriva Respimat were then highlighted in a pooled analysis in 2010 which revealed a numerically greater incidence of all-cause fatality in the Spiriva Respimat group when compared with placebo. Datamonitor Healthcare believes that it is this safety concern that has prevented the launch of Spiriva Respimat in the US and spurred on the TIOSPIR safety trial.
Development of combination LABA/LAMA inhaler supported by olodaterol Respimat results
Boehringer Ingelheim announced Phase III results concerning olodaterol Respimat, which will support the ongoing development of the single-component inhaler. As olodaterol Respimat will be positioned as an add-on maintenance therapy for patients with moderate to severe COPD, Datamonitor Healthcare does not anticipate high sales to be drawn from this product. However, the launch of olodaterol Respimat is a strategy to enable both physicians and patients to become familiar with olodaterol Respimat prior to the launch of Boehringer Ingelheim’s more lucrative once-daily fixed-dose LABA/LAMA inhaler (olodaterol/tiotropium), which is expected to launch in the EU and US by the end of 2015.
The Phase III results announced this week support olodaterol Respimat as an add-on therapy to usual care alone. Usual care in the two 48-week Phase III studies included treatment with long- and short-acting muscarinic antagonists, short-acting beta agonists, inhaled corticosteroids, and xanthines. Boehringer Ingelheim reported that the addition of olodaterol Respimat to usual care can lead to statistically significant improvements in lung function compared to usual care alone (p<0.05).
Novartis prepares Ultibro Breezhaler to become first-in-class once-daily LABA/LAMA inhaler in the EU
The imminent emergence of the LABA/LAMA drug class will be a pivotal event for the COPD market, and Novartis will become the first company to launch a LABA/LAMA in the EU with the pending marketing authorization of Ultibro Breezhaler (QVA149).
The LABA/LAMA drug class is highly anticipated as these new inhalers will simplify treatment for patients while providing efficacy from dual bronchodilator therapy. High uptake is expected, particularly among patients with severe and very severe COPD. A number of big pharma companies hope to realize the potential within this drug class, with Novartis, Boehringer Ingelheim, GlaxoSmithKline, and AstraZeneca all seeking to launch LABA/LAMA inhalers. Indeed, Datamonitor Healthcare forecasts that this drug class alone will generate approximately $3.34bn in sales by 2022.
At the ERS Annual Congress, Novartis presented further analyses to reinforce the message of Ultibro Breezhaler’s efficacy as a bronchodilator maintenance treatment for COPD. Ultibro Breezhaler is a once-daily LABA/LAMA inhaler comprising the two components indacaterol and glycopyrronium. In July 2013, the European Medicines Agency’s (EMA’s) Committee for Medicinal Products for Human Use endorsed Ultibro Breezhaler for approval in the EU. Assuming that the EMA issues marketing authorization, the product will launch as the first once-daily LABA/LAMA inhaler in the EU.
Novartis reported that pooled analyses from the IGNITE clinical program demonstrate that Ultibro Breezhaler provides sustained improvements in lung function and reduces shortness of breath against a number of comparators, including placebo, indacaterol, glycopyrronium, open-label (OL) tiotropium, and salmeterol/fluticasone.
US committee votes in favor of GlaxoSmithKline’s Anoro
Advair (fluticasone/salmeterol) has carried the success of GlaxoSmithKline’s well-established respiratory franchise, generating approximately $8bn in sales for asthma and COPD in 2012. However, Advair’s position within the COPD market is under threat by the launch of pipeline inhalers as well as the emergence of generic inhalers. The threat of generic alternatives to Advair was made all the more real to GlaxoSmithKline with the issue of draft guidance to demonstrate bioequivalence for dry powder inhalers of fluticasone/salmeterol, which was released by the FDA this week.
To preserve market share and boost GlaxoSmithKline’s respiratory portfolio the company has developed two novel combination inhalers, Breo and Anoro. The launch of these two inhalers, particularly in the US, will strengthen GlaxoSmithKline’s position within the COPD market. Breo is a dual inhaler of fluticasone (an inhaled corticosteroid) and vilanterol (a LABA), which was approved by the FDA in May 2013, and Anoro is a fixed-dose combination inhaler of umeclidinium (a LAMA) and vilanterol (a LABA).
On 11 September, 2013, the FDA’s PADAC voted 11 to two in favor of Anoro as a once-daily maintenance therapy for the treatment of COPD. Assuming that the FDA approves Anoro, Datamonitor Healthcare believes that the product could launch as the first LABA/LAMA inhaler in the US, providing GlaxoSmithKline with a critical position to establish a foothold within this new drug class prior to the launch of competition from Novartis, Boehringer Ingelheim, AstraZeneca, and Forest. The favorable PADAC vote came despite a cardiovascular safety issue that was highlighted by the committee, specifically that a small imbalance was observed for non-fatal myocardial infarction, which was not observed in the long-term safety study.
LABA/LAMA class will facilitate significant market growth, with fierce in-class competition expected
Datamonitor Healthcare anticipates the LABA/LAMA drug class to experience substantial growth over the next 10 years, generating 31% of total sales in the COPD market (predicted to be worth $11bn by 2022). Success within the LABA/LAMA drug class will be contingent on the appeal of once-daily over twice-daily dosing. Once-daily LABA/LAMA inhalers will certainly provide patients on more complicated treatment regimens with a strong incentive to switch, yet proponents of twice-daily therapy argue that dosing twice a day provides the flexibility to alleviate morning and night-time symptoms. Unsurprisingly, Almirall has taken the former position, highlighting in a recent press release that round-the-clock symptom control with aclidinium can relieve early morning, day, and night-time symptoms. It is likely that Almirall, in conjunction with Forest Laboratories, will seek to demonstrate the benefits of twice-daily dosing with its pipeline LABA/LAMA aclidinium/formoterol inhaler, which the company expects to file for regulatory approval in the EU by the end of 2013.