COPD Phase III study meets primary endpoint

“We are very pleased that SPARK showed a reduction of exacerbations, further demonstrating that QVA149 could improve the lives of patients with COPD,” said Tim Wright, Head of Development, Novartis Pharmaceuticals. “We are looking forward to filing QVA149 initially in Europe and Japan, which will bring us another step closer to providing a full range of innovative COPD medicines to help physicians select the right treatment for the right patient at the right time.”

SPARK met its primary endpoint by demonstrating that patients treated with once-daily (QD) investigational QVA149 for 64 weeks demonstrated a clinically meaningful and statistically significant lower rate of moderate-to-severe COPD exacerbations compared to patients treated with QD glycopyrronium 50 mcg (p=0.038)[1]. The study also showed that the rate of moderate-to-severe exacerbations was numerically lower (p=0.096) in patients on QVA149 compared to open-label (OL) tiotropium 18 mcg[1].

A further analysis of the data demonstrated that QVA149 was statistically significantly more effective in reducing the overall rate of all exacerbations (mild, moderate and severe) compared to glycopyrronium 50 mcg (p=0.001) and OL tiotropium 18 mcg (p=0.002)[1]. The adverse event (AE) profile of QVA149 was similar to both glycopyrronium 50 mcg and OL tiotropium 18 mcg[1].

The management of COPD exacerbations is important to both patients and physicians, as exacerbations can impose a significant burden of morbidity, mortality, reduced quality of life and healthcare costs[6],[7]. Frequent exacerbations are linked to an accelerated decline in lung function[8],[9] and patients are also known to have a poorer quality of life[10]. Admissions to hospital due to exacerbations are increasing[11] and patients with more severe underlying disease account for around 70% of the direct medical costs of COPD[12].

SPARK was a 64-week, multi-center, randomized, double-blind, parallel-group, active controlled study designed to evaluate the effect of QVA149 (indacaterol maleate 110 mcg / glycopyrronium 50 mcg) QD versus glycopyrronium 50 mcg and QD OL tiotropium 18 mcg on moderate-to-severe COPD exacerbations in 2,224 patients with severe to very severe COPD[1].

QVA149 is an investigational inhaled, once-daily, fixed-dose combination of the long-acting beta2-adrenergicagonist (LABA) indacaterol maleate, and the investigational long-acting muscarinic antagonist (LAMA) glycopyrronium bromide, being investigated for the treatment of COPD in the Phase III IGNITE clinical trial program. IGNITE is one of the largest international clinical trial programs in COPD comprising 10 studies in total with more than 7,000 patients across 42 countries[1-5],[13-20]. The first five studies (ILLUMINATE, SHINE, BRIGHT, ENLIGHTEN, SPARK) have already completed in 2012 with three additional studies (BLAZE, ARISE, BEACON) expected to complete by the end of the year. The studies are designed to investigate efficacy, safety and tolerability, exercise endurance, exacerbations, breathlessness and quality of life[1-5],[13-17].

Novartis is committed to addressing the unmet medical needs of COPD patients and improving their quality of life by providing innovative medicines and devices.

In addition to investigational QVA149, the Novartis COPD portfolio also includes Onbrez® Breezhaler® (indacaterol maleate) and glycopyrronium bromide (Seebri® Breezhaler®).

Onbrez® Breezhaler® (indacaterol maleate) is a QD LABA that is currently the only COPD treatment on the market to offer clinically relevant 24-hour bronchodilation combined with a rapid onset of action of five minutes at first dose, as demonstrated in the INERGIZE Phase III trial program[21-24]. Onbrez® Breezhaler® has also shown significant improvement in breathlessness scores compared to placebo and OL tiotropium 18 mcg[21]. Onbrez® Breezhaler® was first launched in the EU in 150 mcg and 300 mcg once-daily doses. Most recently, Novartis launched the 75 mcg once-daily dose in the US under the brand name ArcaptaTM NeohalerTM. It is also available as a 150 mcg once-daily dose in Japan under the brand name Onbrez® Inhalation Capsules.

Glycopyrronium bromide (Seebri® Breezhaler®) is an investigational LAMA developed as a once-daily inhaled maintenance therapy for the treatment of COPD. Phase III data from the GLOW1, 2 and 3 studies demonstrated that glycopyrronium bromide increased patients’ lung function over a 24-hour period compared to placebo with a fast onset of action at first dose, and improved exercise endurance versus placebo[25-27]. Glycopyrronium bromide was licensed to Novartis in April 2005 by Vectura and its co-development partner Sosei.

All of the Novartis COPD portfolio products are being developed for delivery via the Breezhaler® device, a single-dose dry powder inhaler (SDDPI), which has low air flow resistance, making it particularly suitable for patients with airflow limitation, such as COPD patients. The Breezhaler® device allows patients to hear, feel and see that they have taken the drug correctly[18].

COPD is a progressive disease associated mainly with tobacco smoking, air pollution or occupational exposure, which can cause obstruction of airflow in the lungs resulting in debilitating bouts of breathlessness. It affects an estimated 210 million people worldwide[28] and is predicted to be the third leading cause of death by 2020[29]. Although COPD is often thought of as a disease of the elderly, 50% of patients are estimated to be within the ages of 50 and 65, which means that half of the COPD population are likely to be impacted at the peak of their earning power and family responsibilities[30].

The foregoing release contains forward-looking statements that can be identified by terminology such as “intended,” “expected,” “could,” “looking forward to,” “will,” “being investigated,” “designed,” “committed,” “launched,” or similar expressions, or by express or implied discussions regarding potential regulatory submissions or approvals for QVA149 or regarding potential future revenues from QVA149. You should not place undue reliance on these statements.  Such forward-looking statements reflect the current views of management regarding future events, and involve known and unknown risks, uncertainties and other factors that may cause actual results with QVA149 to be materially different from any future results, performance or achievements expressed or implied by such statements. There can be no guarantee that QVA149 will be submitted or approved for sale in any market, or at any particular time. Nor can there be any guarantee that QVA149 will achieve any particular levels of revenue in the future. In particular, management’s expectations regarding QVA149 could be affected by, among other things, unexpected clinical trial results, including unexpected new clinical data and unexpected additional analysis of existing clinical data; unexpected regulatory actions or delays or government regulation generally; competition in general; government, industry and general public pricing pressures; the company’s ability to obtain or maintain patent or other proprietary intellectual property protection; unexpected manufacturing issues; the impact that the foregoing factors could have on the values attributed to the Novartis Group’s assets and liabilities as recorded in the Group’s consolidated balance sheet, and other risks and factors referred to in Novartis AG’s current Form 20-F on file with the US Securities and Exchange Commission. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those anticipated, believed, estimated or expected. Novartis is providing the information in this press release as of this date and does not undertake any obligation to update any forward-looking statements contained in this press release as a result of new information, future events or otherwise.

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